Help please. Feeling scared. How to decrease expression of SOD - superoxide dismutase?

[vetiver]

I took an extramel/SOD supplement and now I’m dying. I have horrible joint pain and fatigue and dry eyes and this constant feeling of inflammation that only seems to get worse day by day.

I’m having a real bad time, I can’t find anything or think of anything that could reverse this process.


“Unexpectedly, overexpression of superoxide dismutase 1 (SOD1) in rd1 mice increased oxidative damage and accelerated cone cell death. “

Increased Expression of Catalase and Superoxide Dismutase 2 Reduces Cone Cell Death in Retinitis Pigmentosa

Oxidative and nitrosative damage are major contributors to cone cell death in retinitis pigmentosa (RP). In this study, we explored the effects of augmenting components of the endogenous antioxidant defense system in models of RP, rd1, and rd10 mice. Unexpectedly, overexpression of superoxide...

www.cell.com

“Since the three enzymes of the antioxidant system are susceptible to at least one of the oxidative reactive molecules, in the case of high oxidative stresses such an inhibition could take place, leading to an irreversible autocatalytical process in which the production rate of the oxidants will continuously increase, leading to cell death.”


“In the present investigation, it was found that the formation of hydroxyl radicals was enhanced by SOD in the standard reaction mixture under UVA irradiation. Since hydroxyl radicals are known to be very reactive towards proteins, lipids, and nucleic acids, the hydroxyl radicals observed here might have been a trigger for cell damage and might have had highly deleterious effects on cells.

This finding is quite surprising, since SOD is generally considered to be an antioxidant. It might have deleterious effects rather than protective ones with respect to the cytotoxicity of active oxygen species under conditions like those prevailing in the present system. Some investigators have reported that SOD enhances cytotoxicity due to active oxygen species.23–27)”

 

[Rinse & rePeat]

I took an extramel/SOD supplement and now I’m dying. I have horrible joint pain and fatigue and dry eyes and this constant feeling of inflammation that only seems to get worse day by day.

I’m having a real bad time, I can’t find anything or think of anything that could reverse this process.


“Unexpectedly, overexpression of superoxide dismutase 1 (SOD1) in rd1 mice increased oxidative damage and accelerated cone cell death. “

Increased Expression of Catalase and Superoxide Dismutase 2 Reduces Cone Cell Death in Retinitis Pigmentosa

Oxidative and nitrosative damage are major contributors to cone cell death in retinitis pigmentosa (RP). In this study, we explored the effects of augmenting components of the endogenous antioxidant defense system in models of RP, rd1, and rd10 mice. Unexpectedly, overexpression of superoxide...

www.cell.com

“Since the three enzymes of the antioxidant system are susceptible to at least one of the oxidative reactive molecules, in the case of high oxidative stresses such an inhibition could take place, leading to an irreversible autocatalytical process in which the production rate of the oxidants will continuously increase, leading to cell death.”


“In the present investigation, it was found that the formation of hydroxyl radicals was enhanced by SOD in the standard reaction mixture under UVA irradiation. Since hydroxyl radicals are known to be very reactive towards proteins, lipids, and nucleic acids, the hydroxyl radicals observed here might have been a trigger for cell damage and might have had highly deleterious effects on cells.

This finding is quite surprising, since SOD is generally considered to be an antioxidant. It might have deleterious effects rather than protective ones with respect to the cytotoxicity of active oxygen species under conditions like those prevailing in the present system. Some investigators have reported that SOD enhances cytotoxicity due to active oxygen species.23–27)”

I don’t know anything about this, I would go for some Progest-E to calm your nerves, but I am not sure that is an option for you. When did this all start?

 

[Rinse & rePeat]

I found this…

..”the clinical application of SOD as a therapeutic agent has been limited due to its extremely rapid plasma clearance time, instability, and immunogenicity in vivo. Several strategies have been proposed to overcome these problems, including the use of SOD conjugates with alginate–chitosan”

Superoxide Dismutase - an overview | ScienceDirect Topics

www.sciencedirect.com

 

[vetiver]

Oh interesting thankyou. I have some chitosan here. It’s been around 5 days since I took it.

I tried progesterone but it increases SOD unfortunately. A lot of things do.

I think selenium might be helping, too early to say but it raises glutathione transferase and I suspect my reaction is from SOD producing too much hydrogen peroxide that isn’t being converted due to a lack of catalase and/or glutathione transferase which is then causing oxidative damage.

I found this…

..”the clinical application of SOD as a therapeutic agent has been limited due to its extremely rapid plasma clearance time, instability, and immunogenicity in vivo. Several strategies have been proposed to overcome these problems, including the use of SOD conjugates with alginate–chitosan”

Superoxide Dismutase - an overview | ScienceDirect Topics

www.sciencedirect.com

 

[vetiver]

I really think the common denominator is hydrogen peroxide as I have had similar very extreme reactions to taking iodine as well as methylene blue which both raise H₂O₂

 

[Motorneuron]

@vetiver
Very interesting thread also for the probable correlations with the symptoms of spinal and motor neuron damage.

As you say it is very paradoxical, because anyone tries to "increase" the activity of SOD (there are two if I'm not mistaken) together with catalase and GPX. It should largely depend on zinc/copper.

Do you have mimetic symptoms of ALS?

Not sure if methylene blue directly increases H2O2, rather it should help conversion to water while avoiding neurotoxicity.

Keep me updated, I'm very interested. In the meantime, you could insert some pure curcumin or eugenol in small doses and see what happens

 

[Dainis Spainis]

I am wondering what could sauna do to you...

 

[UG Krishnamurti]

The NRAMP family of metal-ion transporters [2006]
"What are the expected consequences of divalent metal depletion from the phagosomal space on the antimicrobial defense system of phagocytes? Intracellular pathogens such as Salmonella typhimurium, M. tuberculosis, Mycobacterium bovis, and Leishmania donovani synthesize superoxide dismutase (58–60), an important component of the intracellular survival strategy of these pathogens. Importantly, Mn2+ is an essential cofactor for superoxide dismutase and elimination of the cation from the phagosomal milieu would result in inactivation of this protective enzymatic activity, resulting in a net enhancement of the bactericidal activity of the phagocyte."

Fig. 3. Two hypotheses for the function of Nramp1 in macrophage–pathogen interaction.
The infecting bacterium is taken into the macrophage phagosome where it is challenged by reactive oxygen components. The bacterium protects itself by producing metalloenzymes, such as catalase (Cat) and superoxide dismutase (SOD) that can neutralize the toxic agents.

The metal-ion depletion of the phagosomal lumen restricts the pathogen ability to produce and activate the protective enzymes (such as catalase and superoxide dismutase), and prevents the propagation (spreading) of the ingested microorganisms.
(B) Nramp1 operates as an antiporter of protons and metal-ions. It transports metal-ions from the cytoplasm into the phagosomal lumen. The accumulated metal-ions in the phagosome generate highly reactive hydroxyl radicals, which contribute to the bacteriostatic effect of the macrophage.

RP: Lipid peroxidation is involved in the degenerative diseases, and many publications argue that fructose increases it, despite the fact that it can increase the production of uric acid, which is a major component of our endogenous antioxidant system (e.g., Waring, et al., 2003). When rats were fed for 8 weeks on a diet with 18% fructose and 11% saturated fatty acids, the content of polyunsatured fats in the blood decreased, as they had in the Brown, et al., experiment, and their total antioxidant status was increased (Girard, et al., 2005). When stroke-prone spontaneously hypertensive rats were given 60% fructose, superoxide dismutase in their liver was increased, and the authors suggest that this "may constitute an early protective mechanism" (Brosnan and Carkner, 2008). When people were given a 300 calorie drink containing glucose, or fructose, or orange juice, those receiving the glucose had a large increase in oxidative and inflammatory stress (reactive oxygen species, and NF-kappaB binding), and those changes were absent in those receiving the fructose or orange juice (Ghanim, et al., 2007).

Free radicals, antioxidants and functional foods: Impact on human health
Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
Some internally generated sources of free radicals are[8] Mitochondria, Xanthine oxidase ,Peroxisomes, Inflammation, Phagocytosis, Arachidonate pathways, Exercise, Ischemia/reperfusion injury. Some externally generated sources of free radicals are: Cigarette smoke, Environmental pollutants, Radiation, Certain drugs, pesticides, Industrial solvents, Ozone.
Short-term oxidative stress may occur in tissues injured by trauma, infection, heat injury, hyperoxia, toxins, and excessive exercise. These injured tissues produce increased radical generating enzymes (e.g., xanthine oxidase, lipoxygenase, cyclooxygenase) activation of phagocytes [Phagocytes (neutrophils and monocytes) are immune cells that play a critical role in both the early and late stages of immune responses. Their main role is to circulate and migrate through tissues to ingest and destroy both microbes and cellular debris] , release of free iron, copper ions, or a disruption of the electron transport chains of oxidative phosphorylation, producing excess ROS. The initiation, promotion, and progression of cancer, as well as the side-effects of radiation and chemotherapy, have been linked to the imbalance between ROS and the antioxidant defense system. ROS have been implicated in the induction and complications of diabetes mellitus, age-related eye disease, and neurodegenerative diseases such as Parkinson's disease.
Hydroxyl radicals are produced from the Fenton reaction (1) or Haber-Weiss reaction. Thus, they are formed H2O2 and superoxide (O2•−).
Mitochondrial ETC generates superoxide under physiological conditions, and oxidative stress increases ROS production. Mitochondria are the major source of intracellular superoxide production, and damage of mtDNA appears to damage mitochondrial DNA encoded proteins in ETC, causing more superoxide to be produced. Reducing excess amounts of mitochondria-generated superoxide seems important to protecting against oxidative stress related diseases. The reactivity of superoxide is relatively low. However, when elevated levels of NO• are present, nitric oxide binds to mitochondrial ETC-generated superoxide. Subsequently, ONOO− [Peroxynitrite] is formed with the rate constant close to that of the reaction between hydroxyl radical (HO•) and ascorbic acid. Then, ONOO− produces hydroxyl radicals and nitrogen dioxide, and oxidizes and nitrates DNAs, lipids and proteins, etc., and induces apoptosis, autophagy, mitophagy and necrosis (Fig. 2 and and5).5). MnSOD exists in mitochondria (Fig. 3) to block the binding of mitochondrial ETC-generated superoxide with nitric oxide (Fig. 4). This theory, called ”A Mitochondrial Superoxide Theory” (Fig. 4), could explain the initiation of numerous chronic diseases, such as aging and carcinogenesis.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6047868/
Several studies showed that celery contains high levels of phenolic and flavonoid compounds and exhibits significant antioxidant and free radical scavenging activities in vitro. It was found that the n-butanol extract of celery seed modified the glycemic and insulin levels, ameliorated hepatic lipid peroxidation, and improved intracellular glutathione and antioxidant enzymes (mainly superoxide dismutase, catalase, glutathione transferase, and reductase) in streptozotocin-induced diabetic rats. Antioxidant and cyclooxygenase (COX-I and COX-II) inhibitory activities have also been described for several constituents in the celery plant (16). For example, apigenin, an antioxidant, inhibits the production of hydrogen peroxide and IgE, which are responsible for inflammation and allergic responses (47,48). Apigenin also had inhibitory effects on cyclooxygenase and lipoxygenase (49). Li et al. (50) showed that apiin, the flavonoid isolated from celery leaf, possess remarkable antioxidant activities in vitro and in vivo. Apiin effectively scavenged DPPH, OH, and superoxide (O2−) free radicals in vitro. In vivo, apiin also significantly decreased TBARS levels and improved the total antioxidant capacity, and enhanced activities of the enzymes superoxide dismutase, glutathione peroxidase and catalase in serum, brain, heart, liver and kidney of male mice.”

Antioxidants and Polyphenols in Inflammatory Bowel Disease: Ulcerative Colitis and Crohn Disease​

..Thus, curcumin, green tea (epigallocatechin-3-gallate-rich polyphenon E), bilberry anthocyanins, wheat grass juice, resveratrol, superoxide dismutase, and fish oils were shown to be effective in part for the treatment of human inflammatory bowel disease.
The effects of medium-strength electric impulses on human blood
"Significant rises were detected in the serum superoxide dismutase (SOD) activities."

Chronic granulomatous disease [2 Video + DIAGNOSTIC TEST]]
[My interpretation of the video]: So apparently he says that CGD is a lack of enzyme called NADPH Oxidase - which is crucial for creation of superoxide and therefore hydrogen peroxide which is crucial in killing the pathogens. So the NADPH + O2 with the help of NADPH oxidase enzyme create superoxide and than with the help of enzyme superoxide dismutase create hydrogen peroxide. When we are missing the NADPH oxidase the body cannot produce hydrogen peroxide and instead "wall of" the pathogens because it cannot kill them. But another problem is the fact that even if you take hydrogen peroxide endogenously you will not be able to kill the catalase organisms - which are problems in granulomatous disease. That catalase enzyme which are part of the coating of the bacteria inhibit hydrogen peroxide. Because it cannot kill them it "walls them off" which therefore create granulomas and granulomatous disease. So granulomas are walled off catalase based organism according to him.
METHYLENE BLUE AS AN INHIBITOR OF SUPEROXIDE GENERATION BY XANTHINE OXIDASE: A POTENTIAL NEW DRUG FOR THE ATTENUATION OF ISCHEMIA/REPERFUSION INJURY
Upon reoxygenation, a burst of superoxide radicals may be formed in certain cell types by the action of xanthine oxidase upon accumulated hypoxanthine and xanthine substrates [7]. In the presence of suitably chelated iron, a fraction of the superoxide generated by biological sources may participate in the superoxide driven Fenton reaction, in which hydroxyl radical (HO) formation occurs.
There are currently several methods under investigation to prevent or attenuate superoxide and iron mediated injury. The first is the use of antioxidant enzymes such as superoxide dismutase (SOD) and catalase which scavenge and break down superoxide and hydrogen peroxide, respectively [20, 21]. Alternatively, iron chelating compounds such as deferoxamine may inhibit superoxide-initiated injury, presumably by preventing the redox cycling of iron [22, 23]. Another attractive approach may be the use of xanthine oxidase inhibitors [2, 24, 25]. Best known among these inhibitors are the purine analogs, oxypurinol and allopurinol, which bind competitively to the purine binding site of the enzyme, displacing hypoxanthine and xanthine.

ANTIAGING EFFECTS OF KLOTHO​

Klotho gene overexpression extends lifespan by 20–30%.2
Klotho extends lifespan by inhibiting the aging process through a surprising mechanism, that is the induction of insulin resistance.2 Indeed, by inducing the inhibition of insulin/IGF-1 signaling klotho also increases the resistance to oxidative stress at the cellular and subcellular level in mammals. Furthermore, klotho protein activates the forkhead transcription factors (FoxO) that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance.12,27

Nitric Oxide in Systemic Lupus Erythematosus​

"Because catalase removes superoxide, its inactivation may expose cells to increased oxidative stress and accelerate tissue damage or modification".

Offense and Defense in Granulomatous Inflammation Disease [2022]
M. tuberculosis generates and secretes antioxidant enzymes (e.g., superoxide dismutases and glutathione peroxidase), helping them to persist in an abnormal redox environment.
Chapter 4 Calcium in Health and Disease

5.2.4 Amyotrophic Lateral Sclerosis​

Amyotrophic lateral sclerosis is caused by the loss of motor neurons in the motor cortex and the spinal cord [ 225 ]. The molecular/cellular phenotype is characterized by oxidative stress, organelle dysfunctions, and Ca 2+ imbalance [ 226 ]. About 5–10% of ALS cases are familiar, and 20% of them present a mutation in the gene that encodes superoxide dismutase 1 (SOD1) [ 227 ].
Most ALS research is now concentrated on the mutations of SOD1: since the protein is critical in the defense against oxidative stress, the notion that oxidative stress is at the basis of ALS cellular phenotype has traditionally occupied the central stage.

RP: "We compared the effect of a mixed tocopherol preparation with that of alpha-tocopherol alone on superoxide dismutase (SOD) activity and iNOS expression in cultured myocytes exposed to H-R." "Both tocopherol preparations attenuated cell injury. . . .” “However, mixed-tocopherol preparation was much superior to alpha-tocopherol in terms of myocyte protection. . . .” “Lack of efficacy of commercial tocopherol preparations in clinical trials may reflect absence of gamma- and delta-tocopherols."
Chen H, Li D, Saldeen T, Romeo F, Mehta JL,Biochem Biophys Res Commun 2002 "Mixed tocopherol preparation is superior to alpha-tocopherol alone against hypoxia-reoxygenation injury."

Stop chronic kidney disease progression: Time is approaching
The superoxide dismutase-mimetic drug, Tempol, improved elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage that were induced by 5/6 nephrectomy. These results indicate the value of the increased oxidative stress commonly encountered in CKD on the progression of the renal disease. They also highlight the possible value of antioxidant treatment to delay CKD progression[189].

"Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-β/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways."

Protective Effect of Selenium-L-methionine on Radiation-induced Acute Pneumonitis and Lung Fibrosis in Rat.
Selenium-L-methionine can be incorporated into proteins containing methionine, without any detrimental effects on the functions of proteins. Free selenium can also be used for the development of selenocysteine, an amino acid that plays a key role in stimulating antioxidant enzymes such as superoxide dismutase (SOD), thioredoxin reductase (TR), glutathione peroxidases (GPx), and others [21].

 

[Motorneuron]

The NRAMP family of metal-ion transporters [2006]
"What are the expected consequences of divalent metal depletion from the phagosomal space on the antimicrobial defense system of phagocytes? Intracellular pathogens such as Salmonella typhimurium, M. tuberculosis, Mycobacterium bovis, and Leishmania donovani synthesize superoxide dismutase (58–60), an important component of the intracellular survival strategy of these pathogens. Importantly, Mn2+ is an essential cofactor for superoxide dismutase and elimination of the cation from the phagosomal milieu would result in inactivation of this protective enzymatic activity, resulting in a net enhancement of the bactericidal activity of the phagocyte."

Fig. 3. Two hypotheses for the function of Nramp1 in macrophage–pathogen interaction.
The infecting bacterium is taken into the macrophage phagosome where it is challenged by reactive oxygen components. The bacterium protects itself by producing metalloenzymes, such as catalase (Cat) and superoxide dismutase (SOD) that can neutralize the toxic agents.

The metal-ion depletion of the phagosomal lumen restricts the pathogen ability to produce and activate the protective enzymes (such as catalase and superoxide dismutase), and prevents the propagation (spreading) of the ingested microorganisms.
(B) Nramp1 operates as an antiporter of protons and metal-ions. It transports metal-ions from the cytoplasm into the phagosomal lumen. The accumulated metal-ions in the phagosome generate highly reactive hydroxyl radicals, which contribute to the bacteriostatic effect of the macrophage.

RP: Lipid peroxidation is involved in the degenerative diseases, and many publications argue that fructose increases it, despite the fact that it can increase the production of uric acid, which is a major component of our endogenous antioxidant system (e.g., Waring, et al., 2003). When rats were fed for 8 weeks on a diet with 18% fructose and 11% saturated fatty acids, the content of polyunsatured fats in the blood decreased, as they had in the Brown, et al., experiment, and their total antioxidant status was increased (Girard, et al., 2005). When stroke-prone spontaneously hypertensive rats were given 60% fructose, superoxide dismutase in their liver was increased, and the authors suggest that this "may constitute an early protective mechanism" (Brosnan and Carkner, 2008). When people were given a 300 calorie drink containing glucose, or fructose, or orange juice, those receiving the glucose had a large increase in oxidative and inflammatory stress (reactive oxygen species, and NF-kappaB binding), and those changes were absent in those receiving the fructose or orange juice (Ghanim, et al., 2007).

Free radicals, antioxidants and functional foods: Impact on human health
Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
Some internally generated sources of free radicals are[8] Mitochondria, Xanthine oxidase ,Peroxisomes, Inflammation, Phagocytosis, Arachidonate pathways, Exercise, Ischemia/reperfusion injury. Some externally generated sources of free radicals are: Cigarette smoke, Environmental pollutants, Radiation, Certain drugs, pesticides, Industrial solvents, Ozone.
Short-term oxidative stress may occur in tissues injured by trauma, infection, heat injury, hyperoxia, toxins, and excessive exercise. These injured tissues produce increased radical generating enzymes (e.g., xanthine oxidase, lipoxygenase, cyclooxygenase) activation of phagocytes [Phagocytes (neutrophils and monocytes) are immune cells that play a critical role in both the early and late stages of immune responses. Their main role is to circulate and migrate through tissues to ingest and destroy both microbes and cellular debris] , release of free iron, copper ions, or a disruption of the electron transport chains of oxidative phosphorylation, producing excess ROS. The initiation, promotion, and progression of cancer, as well as the side-effects of radiation and chemotherapy, have been linked to the imbalance between ROS and the antioxidant defense system. ROS have been implicated in the induction and complications of diabetes mellitus, age-related eye disease, and neurodegenerative diseases such as Parkinson's disease.
Hydroxyl radicals are produced from the Fenton reaction (1) or Haber-Weiss reaction. Thus, they are formed H2O2 and superoxide (O2•−).
Mitochondrial ETC generates superoxide under physiological conditions, and oxidative stress increases ROS production. Mitochondria are the major source of intracellular superoxide production, and damage of mtDNA appears to damage mitochondrial DNA encoded proteins in ETC, causing more superoxide to be produced. Reducing excess amounts of mitochondria-generated superoxide seems important to protecting against oxidative stress related diseases. The reactivity of superoxide is relatively low. However, when elevated levels of NO• are present, nitric oxide binds to mitochondrial ETC-generated superoxide. Subsequently, ONOO− [Peroxynitrite] is formed with the rate constant close to that of the reaction between hydroxyl radical (HO•) and ascorbic acid. Then, ONOO− produces hydroxyl radicals and nitrogen dioxide, and oxidizes and nitrates DNAs, lipids and proteins, etc., and induces apoptosis, autophagy, mitophagy and necrosis (Fig. 2 and and5).5). MnSOD exists in mitochondria (Fig. 3) to block the binding of mitochondrial ETC-generated superoxide with nitric oxide (Fig. 4). This theory, called ”A Mitochondrial Superoxide Theory” (Fig. 4), could explain the initiation of numerous chronic diseases, such as aging and carcinogenesis.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6047868/
Several studies showed that celery contains high levels of phenolic and flavonoid compounds and exhibits significant antioxidant and free radical scavenging activities in vitro. It was found that the n-butanol extract of celery seed modified the glycemic and insulin levels, ameliorated hepatic lipid peroxidation, and improved intracellular glutathione and antioxidant enzymes (mainly superoxide dismutase, catalase, glutathione transferase, and reductase) in streptozotocin-induced diabetic rats. Antioxidant and cyclooxygenase (COX-I and COX-II) inhibitory activities have also been described for several constituents in the celery plant (16). For example, apigenin, an antioxidant, inhibits the production of hydrogen peroxide and IgE, which are responsible for inflammation and allergic responses (47,48). Apigenin also had inhibitory effects on cyclooxygenase and lipoxygenase (49). Li et al. (50) showed that apiin, the flavonoid isolated from celery leaf, possess remarkable antioxidant activities in vitro and in vivo. Apiin effectively scavenged DPPH, OH, and superoxide (O2−) free radicals in vitro. In vivo, apiin also significantly decreased TBARS levels and improved the total antioxidant capacity, and enhanced activities of the enzymes superoxide dismutase, glutathione peroxidase and catalase in serum, brain, heart, liver and kidney of male mice.”

Antioxidants and Polyphenols in Inflammatory Bowel Disease: Ulcerative Colitis and Crohn Disease​

..Thus, curcumin, green tea (epigallocatechin-3-gallate-rich polyphenon E), bilberry anthocyanins, wheat grass juice, resveratrol, superoxide dismutase, and fish oils were shown to be effective in part for the treatment of human inflammatory bowel disease.
The effects of medium-strength electric impulses on human blood
"Significant rises were detected in the serum superoxide dismutase (SOD) activities."

Chronic granulomatous disease [2 Video + DIAGNOSTIC TEST]]
[My interpretation of the video]: So apparently he says that CGD is a lack of enzyme called NADPH Oxidase - which is crucial for creation of superoxide and therefore hydrogen peroxide which is crucial in killing the pathogens. So the NADPH + O2 with the help of NADPH oxidase enzyme create superoxide and than with the help of enzyme superoxide dismutase create hydrogen peroxide. When we are missing the NADPH oxidase the body cannot produce hydrogen peroxide and instead "wall of" the pathogens because it cannot kill them. But another problem is the fact that even if you take hydrogen peroxide endogenously you will not be able to kill the catalase organisms - which are problems in granulomatous disease. That catalase enzyme which are part of the coating of the bacteria inhibit hydrogen peroxide. Because it cannot kill them it "walls them off" which therefore create granulomas and granulomatous disease. So granulomas are walled off catalase based organism according to him.
METHYLENE BLUE AS AN INHIBITOR OF SUPEROXIDE GENERATION BY XANTHINE OXIDASE: A POTENTIAL NEW DRUG FOR THE ATTENUATION OF ISCHEMIA/REPERFUSION INJURY
Upon reoxygenation, a burst of superoxide radicals may be formed in certain cell types by the action of xanthine oxidase upon accumulated hypoxanthine and xanthine substrates [7]. In the presence of suitably chelated iron, a fraction of the superoxide generated by biological sources may participate in the superoxide driven Fenton reaction, in which hydroxyl radical (HO) formation occurs.
There are currently several methods under investigation to prevent or attenuate superoxide and iron mediated injury. The first is the use of antioxidant enzymes such as superoxide dismutase (SOD) and catalase which scavenge and break down superoxide and hydrogen peroxide, respectively [20, 21]. Alternatively, iron chelating compounds such as deferoxamine may inhibit superoxide-initiated injury, presumably by preventing the redox cycling of iron [22, 23]. Another attractive approach may be the use of xanthine oxidase inhibitors [2, 24, 25]. Best known among these inhibitors are the purine analogs, oxypurinol and allopurinol, which bind competitively to the purine binding site of the enzyme, displacing hypoxanthine and xanthine.

ANTIAGING EFFECTS OF KLOTHO​

Klotho gene overexpression extends lifespan by 20–30%.2
Klotho extends lifespan by inhibiting the aging process through a surprising mechanism, that is the induction of insulin resistance.2 Indeed, by inducing the inhibition of insulin/IGF-1 signaling klotho also increases the resistance to oxidative stress at the cellular and subcellular level in mammals. Furthermore, klotho protein activates the forkhead transcription factors (FoxO) that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance.12,27

Nitric Oxide in Systemic Lupus Erythematosus​

"Because catalase removes superoxide, its inactivation may expose cells to increased oxidative stress and accelerate tissue damage or modification".

Offense and Defense in Granulomatous Inflammation Disease [2022]
M. tuberculosis generates and secretes antioxidant enzymes (e.g., superoxide dismutases and glutathione peroxidase), helping them to persist in an abnormal redox environment.
Chapter 4 Calcium in Health and Disease

5.2.4 Amyotrophic Lateral Sclerosis​

Amyotrophic lateral sclerosis is caused by the loss of motor neurons in the motor cortex and the spinal cord [ 225 ]. The molecular/cellular phenotype is characterized by oxidative stress, organelle dysfunctions, and Ca 2+ imbalance [ 226 ]. About 5–10% of ALS cases are familiar, and 20% of them present a mutation in the gene that encodes superoxide dismutase 1 (SOD1) [ 227 ].
Most ALS research is now concentrated on the mutations of SOD1: since the protein is critical in the defense against oxidative stress, the notion that oxidative stress is at the basis of ALS cellular phenotype has traditionally occupied the central stage.

RP: "We compared the effect of a mixed tocopherol preparation with that of alpha-tocopherol alone on superoxide dismutase (SOD) activity and iNOS expression in cultured myocytes exposed to H-R." "Both tocopherol preparations attenuated cell injury. . . .” “However, mixed-tocopherol preparation was much superior to alpha-tocopherol in terms of myocyte protection. . . .” “Lack of efficacy of commercial tocopherol preparations in clinical trials may reflect absence of gamma- and delta-tocopherols."
Chen H, Li D, Saldeen T, Romeo F, Mehta JL,Biochem Biophys Res Commun 2002 "Mixed tocopherol preparation is superior to alpha-tocopherol alone against hypoxia-reoxygenation injury."

Stop chronic kidney disease progression: Time is approaching
The superoxide dismutase-mimetic drug, Tempol, improved elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage that were induced by 5/6 nephrectomy. These results indicate the value of the increased oxidative stress commonly encountered in CKD on the progression of the renal disease. They also highlight the possible value of antioxidant treatment to delay CKD progression[189].

"Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-β/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways."

Protective Effect of Selenium-L-methionine on Radiation-induced Acute Pneumonitis and Lung Fibrosis in Rat.
Selenium-L-methionine can be incorporated into proteins containing methionine, without any detrimental effects on the functions of proteins. Free selenium can also be used for the development of selenocysteine, an amino acid that plays a key role in stimulating antioxidant enzymes such as superoxide dismutase (SOD), thioredoxin reductase (TR), glutathione peroxidases (GPx), and others [21].

Great information, how to increase KLOTHO ?

 

[UG Krishnamurti]

Great information, how to increase KLOTHO ?

If I remember correctly: low phosphate, vitamin d (I prefer sun exposure), Low 1,25D, Mg, Ca.

 

[vetiver]

treme reactions to taking iodine as well as methylene blue which both raise H₂O₂

The NRAMP family of metal-ion transporters [2006]
"What are the expected consequences of divalent metal depletion from the phagosomal space on the antimicrobial defense system of phagocytes? Intracellular pathogens such as Salmonella typhimurium, M. tuberculosis, Mycobacterium bovis, and Leishmania donovani synthesize superoxide dismutase (58–60), an important component of the intracellular survival strategy of these pathogens. Importantly, Mn2+ is an essential cofactor for superoxide dismutase and elimination of the cation from the phagosomal milieu would result in inactivation of this protective enzymatic activity, resulting in a net enhancement of the bactericidal activity of the phagocyte."

Fig. 3. Two hypotheses for the function of Nramp1 in macrophage–pathogen interaction.
The infecting bacterium is taken into the macrophage phagosome where it is challenged by reactive oxygen components. The bacterium protects itself by producing metalloenzymes, such as catalase (Cat) and superoxide dismutase (SOD) that can neutralize the toxic agents.

The metal-ion depletion of the phagosomal lumen restricts the pathogen ability to produce and activate the protective enzymes (such as catalase and superoxide dismutase), and prevents the propagation (spreading) of the ingested microorganisms.
(B) Nramp1 operates as an antiporter of protons and metal-ions. It transports metal-ions from the cytoplasm into the phagosomal lumen. The accumulated metal-ions in the phagosome generate highly reactive hydroxyl radicals, which contribute to the bacteriostatic effect of the macrophage.

RP: Lipid peroxidation is involved in the degenerative diseases, and many publications argue that fructose increases it, despite the fact that it can increase the production of uric acid, which is a major component of our endogenous antioxidant system (e.g., Waring, et al., 2003). When rats were fed for 8 weeks on a diet with 18% fructose and 11% saturated fatty acids, the content of polyunsatured fats in the blood decreased, as they had in the Brown, et al., experiment, and their total antioxidant status was increased (Girard, et al., 2005). When stroke-prone spontaneously hypertensive rats were given 60% fructose, superoxide dismutase in their liver was increased, and the authors suggest that this "may constitute an early protective mechanism" (Brosnan and Carkner, 2008). When people were given a 300 calorie drink containing glucose, or fructose, or orange juice, those receiving the glucose had a large increase in oxidative and inflammatory stress (reactive oxygen species, and NF-kappaB binding), and those changes were absent in those receiving the fructose or orange juice (Ghanim, et al., 2007).

Free radicals, antioxidants and functional foods: Impact on human health
Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
Some internally generated sources of free radicals are[8] Mitochondria, Xanthine oxidase ,Peroxisomes, Inflammation, Phagocytosis, Arachidonate pathways, Exercise, Ischemia/reperfusion injury. Some externally generated sources of free radicals are: Cigarette smoke, Environmental pollutants, Radiation, Certain drugs, pesticides, Industrial solvents, Ozone.
Short-term oxidative stress may occur in tissues injured by trauma, infection, heat injury, hyperoxia, toxins, and excessive exercise. These injured tissues produce increased radical generating enzymes (e.g., xanthine oxidase, lipoxygenase, cyclooxygenase) activation of phagocytes [Phagocytes (neutrophils and monocytes) are immune cells that play a critical role in both the early and late stages of immune responses. Their main role is to circulate and migrate through tissues to ingest and destroy both microbes and cellular debris] , release of free iron, copper ions, or a disruption of the electron transport chains of oxidative phosphorylation, producing excess ROS. The initiation, promotion, and progression of cancer, as well as the side-effects of radiation and chemotherapy, have been linked to the imbalance between ROS and the antioxidant defense system. ROS have been implicated in the induction and complications of diabetes mellitus, age-related eye disease, and neurodegenerative diseases such as Parkinson's disease.
Hydroxyl radicals are produced from the Fenton reaction (1) or Haber-Weiss reaction. Thus, they are formed H2O2 and superoxide (O2•−).
Mitochondrial ETC generates superoxide under physiological conditions, and oxidative stress increases ROS production. Mitochondria are the major source of intracellular superoxide production, and damage of mtDNA appears to damage mitochondrial DNA encoded proteins in ETC, causing more superoxide to be produced. Reducing excess amounts of mitochondria-generated superoxide seems important to protecting against oxidative stress related diseases. The reactivity of superoxide is relatively low. However, when elevated levels of NO• are present, nitric oxide binds to mitochondrial ETC-generated superoxide. Subsequently, ONOO− [Peroxynitrite] is formed with the rate constant close to that of the reaction between hydroxyl radical (HO•) and ascorbic acid. Then, ONOO− produces hydroxyl radicals and nitrogen dioxide, and oxidizes and nitrates DNAs, lipids and proteins, etc., and induces apoptosis, autophagy, mitophagy and necrosis (Fig. 2 and and5).5). MnSOD exists in mitochondria (Fig. 3) to block the binding of mitochondrial ETC-generated superoxide with nitric oxide (Fig. 4). This theory, called ”A Mitochondrial Superoxide Theory” (Fig. 4), could explain the initiation of numerous chronic diseases, such as aging and carcinogenesis.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6047868/
Several studies showed that celery contains high levels of phenolic and flavonoid compounds and exhibits significant antioxidant and free radical scavenging activities in vitro. It was found that the n-butanol extract of celery seed modified the glycemic and insulin levels, ameliorated hepatic lipid peroxidation, and improved intracellular glutathione and antioxidant enzymes (mainly superoxide dismutase, catalase, glutathione transferase, and reductase) in streptozotocin-induced diabetic rats. Antioxidant and cyclooxygenase (COX-I and COX-II) inhibitory activities have also been described for several constituents in the celery plant (16). For example, apigenin, an antioxidant, inhibits the production of hydrogen peroxide and IgE, which are responsible for inflammation and allergic responses (47,48). Apigenin also had inhibitory effects on cyclooxygenase and lipoxygenase (49). Li et al. (50) showed that apiin, the flavonoid isolated from celery leaf, possess remarkable antioxidant activities in vitro and in vivo. Apiin effectively scavenged DPPH, OH, and superoxide (O2−) free radicals in vitro. In vivo, apiin also significantly decreased TBARS levels and improved the total antioxidant capacity, and enhanced activities of the enzymes superoxide dismutase, glutathione peroxidase and catalase in serum, brain, heart, liver and kidney of male mice.”

Antioxidants and Polyphenols in Inflammatory Bowel Disease: Ulcerative Colitis and Crohn Disease​

..Thus, curcumin, green tea (epigallocatechin-3-gallate-rich polyphenon E), bilberry anthocyanins, wheat grass juice, resveratrol, superoxide dismutase, and fish oils were shown to be effective in part for the treatment of human inflammatory bowel disease.
The effects of medium-strength electric impulses on human blood
"Significant rises were detected in the serum superoxide dismutase (SOD) activities."

Chronic granulomatous disease [2 Video + DIAGNOSTIC TEST]]
[My interpretation of the video]: So apparently he says that CGD is a lack of enzyme called NADPH Oxidase - which is crucial for creation of superoxide and therefore hydrogen peroxide which is crucial in killing the pathogens. So the NADPH + O2 with the help of NADPH oxidase enzyme create superoxide and than with the help of enzyme superoxide dismutase create hydrogen peroxide. When we are missing the NADPH oxidase the body cannot produce hydrogen peroxide and instead "wall of" the pathogens because it cannot kill them. But another problem is the fact that even if you take hydrogen peroxide endogenously you will not be able to kill the catalase organisms - which are problems in granulomatous disease. That catalase enzyme which are part of the coating of the bacteria inhibit hydrogen peroxide. Because it cannot kill them it "walls them off" which therefore create granulomas and granulomatous disease. So granulomas are walled off catalase based organism according to him.
METHYLENE BLUE AS AN INHIBITOR OF SUPEROXIDE GENERATION BY XANTHINE OXIDASE: A POTENTIAL NEW DRUG FOR THE ATTENUATION OF ISCHEMIA/REPERFUSION INJURY
Upon reoxygenation, a burst of superoxide radicals may be formed in certain cell types by the action of xanthine oxidase upon accumulated hypoxanthine and xanthine substrates [7]. In the presence of suitably chelated iron, a fraction of the superoxide generated by biological sources may participate in the superoxide driven Fenton reaction, in which hydroxyl radical (HO) formation occurs.
There are currently several methods under investigation to prevent or attenuate superoxide and iron mediated injury. The first is the use of antioxidant enzymes such as superoxide dismutase (SOD) and catalase which scavenge and break down superoxide and hydrogen peroxide, respectively [20, 21]. Alternatively, iron chelating compounds such as deferoxamine may inhibit superoxide-initiated injury, presumably by preventing the redox cycling of iron [22, 23]. Another attractive approach may be the use of xanthine oxidase inhibitors [2, 24, 25]. Best known among these inhibitors are the purine analogs, oxypurinol and allopurinol, which bind competitively to the purine binding site of the enzyme, displacing hypoxanthine and xanthine.

ANTIAGING EFFECTS OF KLOTHO​

Klotho gene overexpression extends lifespan by 20–30%.2
Klotho extends lifespan by inhibiting the aging process through a surprising mechanism, that is the induction of insulin resistance.2 Indeed, by inducing the inhibition of insulin/IGF-1 signaling klotho also increases the resistance to oxidative stress at the cellular and subcellular level in mammals. Furthermore, klotho protein activates the forkhead transcription factors (FoxO) that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance.12,27

Nitric Oxide in Systemic Lupus Erythematosus​

"Because catalase removes superoxide, its inactivation may expose cells to increased oxidative stress and accelerate tissue damage or modification".

Offense and Defense in Granulomatous Inflammation Disease [2022]
M. tuberculosis generates and secretes antioxidant enzymes (e.g., superoxide dismutases and glutathione peroxidase), helping them to persist in an abnormal redox environment.
Chapter 4 Calcium in Health and Disease

5.2.4 Amyotrophic Lateral Sclerosis​

Amyotrophic lateral sclerosis is caused by the loss of motor neurons in the motor cortex and the spinal cord [ 225 ]. The molecular/cellular phenotype is characterized by oxidative stress, organelle dysfunctions, and Ca 2+ imbalance [ 226 ]. About 5–10% of ALS cases are familiar, and 20% of them present a mutation in the gene that encodes superoxide dismutase 1 (SOD1) [ 227 ].
Most ALS research is now concentrated on the mutations of SOD1: since the protein is critical in the defense against oxidative stress, the notion that oxidative stress is at the basis of ALS cellular phenotype has traditionally occupied the central stage.

RP: "We compared the effect of a mixed tocopherol preparation with that of alpha-tocopherol alone on superoxide dismutase (SOD) activity and iNOS expression in cultured myocytes exposed to H-R." "Both tocopherol preparations attenuated cell injury. . . .” “However, mixed-tocopherol preparation was much superior to alpha-tocopherol in terms of myocyte protection. . . .” “Lack of efficacy of commercial tocopherol preparations in clinical trials may reflect absence of gamma- and delta-tocopherols."
Chen H, Li D, Saldeen T, Romeo F, Mehta JL,Biochem Biophys Res Commun 2002 "Mixed tocopherol preparation is superior to alpha-tocopherol alone against hypoxia-reoxygenation injury."

Stop chronic kidney disease progression: Time is approaching
The superoxide dismutase-mimetic drug, Tempol, improved elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage that were induced by 5/6 nephrectomy. These results indicate the value of the increased oxidative stress commonly encountered in CKD on the progression of the renal disease. They also highlight the possible value of antioxidant treatment to delay CKD progression[189].

"Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-β/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways."

Protective Effect of Selenium-L-methionine on Radiation-induced Acute Pneumonitis and Lung Fibrosis in Rat.
Selenium-L-methionine can be incorporated into proteins containing methionine, without any detrimental effects on the functions of proteins. Free selenium can also be used for the development of selenocysteine, an amino acid that plays a key role in stimulating antioxidant enzymes such as superoxide dismutase (SOD), thioredoxin reductase (TR), glutathione peroxidases (GPx), and others [21].

Interesting, thankyou! I cannot tolerate much sugar or fructose right now. Selenium seems to be the one thing that makes the most noticeable difference and maybe alpha lipoic acid. Everything else only seems to make things worse incl vitamin e, aspirin. I do have some methylene blue I’ve been scared to try since my last reaction which I experienced after a few minimal doses had accumulated and then I took some uridine, the effect lasted for over a month. Have been contemplating trying the smallest amount possible.

Immediately after the SOD reaction I started drinking decaf green tea as it upregulates SOD (also catalase), I had assumed taking it caused some kind of downregulation. I thought I was experiencing an improvement but then I’m fairly certain it made things worse. Was probably doing both.

Interestingly apigenin (extract) is another thing I’ve had a similar very extreme protracted reaction to taking the most minimal dose one time, I coudln’t explain it at the time, I thought maybe it was bc of its MAOI properties as I appear to be sensitive to any MAOIs but this explanation makes more sense to me. I must have something broken in the chain.

Have been too afraid to try vitamin c, I suspect it would create more oxidative damage.

 

[vetiver]

@vetiver
Very interesting thread also for the probable correlations with the symptoms of spinal and motor neuron damage.

As you say it is very paradoxical, because anyone tries to "increase" the activity of SOD (there are two if I'm not mistaken) together with catalase and GPX. It should largely depend on zinc/copper.

Do you have mimetic symptoms of ALS?

Not sure if methylene blue directly increases H2O2, rather it should help conversion to water while avoiding neurotoxicity.

Keep me updated, I'm very interested. In the meantime, you could insert some pure curcumin or eugenol in small doses and see what happens

Yes I would say it’s affected my spine and motor neurons the most and has a similar profile to ALS.

Curcumin seems to have paradoxical effects on SOD? Eugenol sounds promising. Interestingly I have some myrcene, a terpene that decreases SOD and increases gpx. I’ve used it in the past for pain and would always find myself craving it and becoming fixated on the smell.

I had taken some quercetin at the same time as the SOD, I was doing a kitchen sink approach to healing acute gastritis and it’s helped me in the past when dealing with acute symptoms. I found a study that says it can reduce catalase which might also explain some of my reaction. Pretty sure I don’t have gastritis anymore.

Going to be very careful with antioxidants from now on.

 

[vetiver]

I have been feeling like this would be good.

I am wondering what could sauna do to you...

 

[Motorneuron]

@vetiver How are you ? Did you know that selenium lowers SOD activity? I have now seen old notes