Ivermectin - How safe is it?

[Perry Staltic]

What's the claimed mechanism of action of Ivermectin? Is it even supposed to work against "viruses?"

The two MOA that impress me the most are it's abilities to disrupt viral binding to ACE2 (antiviral) and to maintain ATP under hypoxic conditions.

The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article

https://www.nature.com/articles/s41429-021-00430-5.pdf

 

[Perry Staltic]

IVM is one of the safest pharmaceuticals in existence.

 

[Perry Staltic]

IVM is included in what is called the triumvirate of drugs: penicillin, aspirin, ivermectin.

 

[Braveheart]

IVM is one of the safest pharmaceuticals in existence.

 

[Homo Consumericus]

What's the claimed mechanism of action of Ivermectin? Is it even supposed to work against "viruses?"

No idea. I studied accounting, not biochemistry. But the success of Indian provinces like Goa and others paint a distinct picture. Listen to a primary medical professional:

DR. LENNY DA COSTA - THE TRUE STORY OF IVERMECTIN IN INDIA

View DR. LENNY DA COSTA - THE TRUE STORY OF IVERMECTIN IN INDIA on Odysee

odysee.com

Somia Swaminathan (Indian who works for the WHO) faces the death penalty (Indian Bar Association sues WHO scientist over Ivermectin)
for having tweeted 1 year ago that Ivermectin was dangerous. The provinces who listened to her have more than 10 times the death rate of the ones who followed sound science. Here is the sound science:

https://ivmmeta.com/

 

[Peatness]

View: https://twitter.com/BarnettforAZ/status/1434518268543262726

 

[Mito]

Me:
Ivermectin is getting a lot of attention and it seems it has become the new superstar instead of or alongside HCQ. Do you think it is as effective and safe as many are making it out to be? It seems to be a relatively new drug compared to things like MB and Aspirin? Thank you.

https://www.nature.com/articles/s41429-021-00430-5.pdf

Ray:
A few small doses for treatment are safe, but I don’t think it’s safe enough to use for preventive purposes, continuing.

1
J Agric Food Chem. 2016 Sep 14;64(36):6895-902.
doi: 10.1021/acs.jafc.6b02812. Epub 2016 Sep 1.
Avermectin Confers Its Cytotoxic Effects by Inducing DNA Damage and Mitochondria-Associated Apoptosis
Yang Zhang 1 , Mingming Luo 1 , Wenping Xu 1 , Mingjun Yang 1 , Bo Wang 1 , Jufang Gao 2 , Yaxiao Li 3 , Liming Tao 1
Avermectin (AVM) has been widely used in agriculture and animal husbandry on the basis of its broad spectrum of effective anthelmintic activity and specificity targets. However, AVM induction of cytotoxicity through DNA damage is remains elusive. Here we investigate the cytotoxic effects of AVM in human nontarget cells in vitro. We clarify that AVM inhibited the viability of HeLa cells and enhanced apoptosis. We have used alkaline comet assay and γH2AX foci formation to detect DNA damage of HeLa cells. As expected, we found AVM caused DNA double-strand breaks in HeLa cells, as measured by significance of comet assay parameters (e.g., tail DNA) and increases of γH2AX foci in HeLa cells. Moreover, established assays of cytotoxicity were performed to characterize the mechanism of AVM toxicity on HeLa cells. The results demonstrated the collapse of mitochondrial membrane potential, and up-regulating the expression level of Bax/Bcl-2 resulted in a release of cytochrome c into cytosol as well as the activation of caspase-9/-3 and cleavage of poly(ADP-ribose) polymerase (PARP). We conclude that AVM has a potential risk to human health by inducing human cell DNA damage and mitochondria-associated apoptosis.
Keywords: DNA damage; apoptosis; avermectin; cytotoxic effects; mitochondrial pathway.

2
Toxicol In Vitro. 2012 Feb;26(1):51-6.
doi: 10.1016/j.tiv.2011.10.007. Epub 2011 Oct 17.
Abamectin affects the bioenergetics of liver mitochondria: A potential mechanism of hepatotoxicity
Juliana C Castanha Zanoli 1 , Marcos A Maioli, Hyllana C D Medeiros, Fábio E Mingatto
Free article
Abstract
Abamectin (ABA) is a macrocyclic lactone of the avermectin family used worldwide as an antiparasitic agent in farm animals and pets and as the active ingredient of insecticides and nematicides. In this study, the effects of abamectin on the bioenergetics of mitochondria isolated from rat liver were evaluated. Mitochondria are responsible for converting the energy released by electron transport and stored as the binding energy molecule ATP. Xenobiotics that interfere with its synthesis or utilization can be acutely or chronically toxic. Abamectin (5-25μM) caused concentration-dependent inhibition of the respiratory chain without affecting the membrane potential or the activity of enzymes NADH dehydrogenase or succinate dehydrogenase. This behavior is similar to oligomycin and carboxyatractyloside and suggests direct action on F(o)F(1)-ATPase and/or the adenine nucleotide translocator (ANT). ABA more pronouncedly inhibited ATPase phosphohydrolase activity in intact, uncoupled mitochondria than in freeze-thawed disrupted mitochondria. ADP-stimulated depolarization of the mitochondrial membrane potential was also inhibited by ABA. Our results indicate that ABA interacts more specifically with the ANT, resulting in functional inhibition of the translocator with consequent impairment of mitochondrial bioenergetics. This effect could be involved in the ABA toxicity to hepatocytes.
Copyright © 2011 Elsevier Ltd. All rights reserved.

3
Toxicol In Vitro. 2013 Mar;27(2):570-9.
doi: 10.1016/j.tiv.2012.10.017. Epub 2012 Nov 6.
The role of mitochondria and biotransformation in abamectin-induced cytotoxicity in isolated rat hepatocytes
Marcos A Maioli 1 , Hyllana C D de Medeiros, Marieli Guelfi, Vitor Trinca, Flávia T V Pereira, Fábio E Mingatto
Free article
Abstract
Abamectin (ABA), which belongs to the family of avermectins, is used as a parasiticide; however, ABA poisoning can impair liver function. In a previous study using isolated rat liver mitochondria, we observed that ABA inhibited the activity of adenine nucleotide translocator and FoF1-ATPase. The aim of this study was to characterize the mechanism of ABA toxicity in isolated rat hepatocytes and to evaluate whether this effect is dependent on its metabolism. The toxicity of ABA was assessed by monitoring oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, cell viability, intracellular Ca(2+) homeostasis, release of cytochrome c, caspase 3 activity and necrotic cell death. ABA reduces cellular respiration in cells energized with glutamate and malate or succinate. The hepatocytes that were previously incubated with proadifen, a cytochrome P450 inhibitor, are more sensitive to the compound as observed by a rapid decrease in the mitochondrial membrane potential accompanied by reductions in ATP concentration and cell viability and a disruption of intracellular Ca(2+) homeostasis followed by necrosis. Our results indicate that ABA biotransformation reduces its toxicity, and its toxic action is related to the inhibition of mitochondrial activity, which leads to decreased synthesis of ATP followed by cell death.
Copyright © 2012 Elsevier Ltd. All rights reserved.

4
Tsitol Genet. Sep-Oct 2011;45(5):58-64.
[Avermectin effects on ultrastructure characteristics of the loach embryos]
[Article in Ukrainian]
S M Mandzynets, O R Kulachkovskyĭ, M V Bura
No abstract available

5
Chemosphere. 2013 Nov;93(10):2528-34.
doi: 10.1016/j.chemosphere.2013.09.058. Epub 2013 Oct 14.
Avermectin induced inflammation damage in king pigeon brain
Li-Jie Chen 1 , Bao-Hong Sun, Jian Ping Qu, Shiwen Xu, Shu Li
To determine the effect of Avermectin (AVM) on inflammation damage in king pigeon brain, eighty two-month-old American king pigeons were randomly divided into four groups, and were fed with either commercial diet or AVM-supplemented diet containing 20 mg kg(-1)diet, 40 mg kg(-1)diet, and 60 mg kg(-1)diet AVM for 30, 60 and 90 d, respectively. Then, the expression level of inflammatory factors (iNOS, PTGEs, NF-κB), histological damage, and ultra-structural damage were examined. It showed that AVM caused higher expressions (P<0.05) of iNOS, PTGEs, NF-κB with disorganized histological and ultra-structural structures in cerebrum, cerebellum, and optic lobe. Meanwhile, inflammatory and histopathological damage were induced by AVM in king pigeon brains. In addition, the main targeted organelle in nervous system was mitochondria, which indicated that mitochondria may be relevant to the process of inflammation induced by AVM. To our best knowledge, this is the first report to study the toxic effect of AVM on inflammatory damage in king pigeon. Thus, the information presented in this study is believed to be helpful in supplementing data for further AVM toxicity study.
Keywords: Avermectin; Brain; Inflammatory damage; King pigeon.
Copyright © 2013 Elsevier Ltd. All rights reserved.

6
Ecotoxicol Environ Saf. 2013 Dec;98:74-81.
doi: 10.1016/j.ecoenv.2013.09.021. Epub 2013 Oct 15.
Avermectin induced liver injury in pigeon: mechanisms of apoptosis and oxidative stress
Wen-Jun Zhu 1 , Ming Li, Ci Liu, Jian-Ping Qu, Ya-Hong Min, Shi-Wen Xu, Shu Li
Extensive use of avermectin (AVM) can result in environment pollution, and it is important to evaluate the potential impact this antibiotic has on ecological systems. Few published literatures have discussed the liver injury mechanisms induced by AVM on birds. In this study, pigeons were exposed to feed containing AVM (0, 20, 40 and 60 mg/kg diet) for 30, 60, 90 days respectively. The results showed that AVM increased the number of apoptosis and the expression level of caspase-3, 8, fas mRNA in the liver of pigeons. Ultrastructural alterations, including mitochondrial damage and chromatin aggregation, become severe with increase exposure dose. Exposure to AVM induced significant changes in antioxidant enzyme {superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)} activities and malondialdehyde (MDA) content, augmented protein carbonyl (PCO) content and DNA-protein crosslink (DPC) coefficient, in a concentration-dependent manner in the liver of pigeons. Our results show that AVM has toxic effect in pigeon liver, and the mechanism of injury caused by AVM is closely related to apoptosis and oxidative stress.
Keywords: 2,4-dinitrophenylhydrazine; AVM; Apoptosis; Avermectin; DNA–protein crosslinks; DNPH; DPC; EDTA; FasL; GSH-Px; Liver; MDA; Oxidative stress; PCO; Pigeon; ROS; SOD; ethylenediamine tetraacetic acid; fas ligand; glutathione peroxidase; malondialdehyde; protein carbonyl; reactive oxygen species; superoxide dismutase.
© 2013 Elsevier Inc. All rights reserved.

7
Ecotoxicol Environ Saf. 2021 Jun 1;215:112129.
doi: 10.1016/j.ecoenv.2021.112129. Epub 2021 Mar 16.
Avermectin induced DNA damage to the apoptosis and autophagy in human lung epithelial A549 cells
Lin Diao 1 , Ning Tang 1 , Cheng Zhang 2 , Jiagao Cheng 1 , Zhenhai Zhang 1 , Siyu Wang 1 , Can Wu 1 , Lutong Zhang 1 , Liming Tao 1 , Zhong Li 1 , Yang Zhang 3
Free article
Abstract
Avermectin (AVM), as a biological insecticide, is widely used in agriculture and forestry production globally. However, inhalation of AVM may pose a risk, and the lung is the direct target, but the cytotoxicity of AVM on human lung cells is still unclear. Here, we attempted to elucidate the cytotoxic effect and molecular mechanism of AVM on human lung A549 cells. The results indicated that AVM inhibits cell proliferation, and enhances programmed cell death (apoptosis and autophagy). In addition, we found the AVM-treated cells showed an obvious drop in mitochondrial membrane potential and LC3-I/II, increased ROS production, DNA double-strand breaks, caspase-3/9 activated, PARP cleaved, cytochrome c and Bax/Bcl-2 content rise. The results showed that AVM induced mitochondria-related apoptosis and autophagy in lung A549 cells. These results indicate that AVM can pose a potential threat to human health by inducing DNA damage and programmed cell death.
Keywords: Avermectin; Cytotoxicity; DNA damage; Human A549 cells; Programmed cell death.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

8
Methods Cell Biol. 2021;165:153-161.
doi: 10.1016/bs.mcb.2020.10.010. Epub 2020 Nov 18.
Monitoring selective autophagy of mitochondria using super-resolution microscopy
Ziyue Li 1 , Nicholas T Ktistakis 2
Selective elimination of damaged mitochondria via macroautophagy (mitophagy) is a conserved cellular process that plays an important role in organismal health. In recent years mitophagy has been studied in parallel to the more general, non-selective autophagy pathway induced in response to amino acid starvation with important similarities and differences noted between the two. The elaborate sequence of membrane rearrangements that give rise to autophagosomes in the non-selective pathway have their counterpart in mitophagy, but with the addition of other factors, such as a ubiquitin mark and mitophagy receptors, which mediate cargo recognition. In some types of mitophagy such as the one induced by ivermectin, the forming autophagosomal structure contains six different elements: the targeted mitochondrial fragment, a section of endoplasmic reticulum that provides a cradle, a ubiquitin layer, the mitophagy receptors and the early and late autophagosomal proteins/membranes. Super-resolution microscopy is ideally suited to investigate the spatial relationships between these elements that converge together but retain some distinctive localization, and we provide here a general protocol that can be used for mammalian cells.
Keywords: Autophagy; Endoplasmic reticulum; Ivermectin; Mitochondria; Mitophagy; Structured illumination microscopy.

 

[Birdie]

I'll hold onto Ivermectin for an emergency and am using Vitamin D, aspirin, a little Benadryl, progesterone as Peat advises. I also use B12 and once a week HCQ, but am considering stopping the HCQ and saving it like the IVM. A little Zinc too for us btw and many things Peat.

Vileplume said:
Me: If the spike proteins are so easily transmissible and so dangerous, might ivermectin and HCQ be reasonable prophylactic measures for someone exposed to vaccinated people daily?

RP: Ivermectin has been associated with brain damage in a small percentage of users, so I don’t think it’s suitable for prolonged preventive use. Vitamin D, aspirin, antihistamines, aspirin, progesterone, etc. are safer.

 

[gaze]

i'm no fan of ivermectin but reading all the cliche, low intelligence horse jokes from self-righteous vaccinated people who think taking a vaccine makes them morally superior has been one of the more annoying aspects of the pandemic so far

 

[Birdie]

Picked up some IVM today. Walgreens had been out of it for a few days. I'm not one of those who believe the horse type is in any inferior though. The veterinary meds are often the same as human ones. For example, my fish amoxicillin is exactly the same pill as human amoxicillin.
The horse paste will have different additives, but probably no worse than the ones used in pills for humans. I haven't checked since I won't be using it long term, only possibly in an emergency.

 

[Braveheart]

Picked up some IVM today. Walgreens had been out of it for a few days. I'm not one of those who believe the horse type is in any inferior though. The veterinary meds are often the same as human ones. For example, my fish amoxicillin is exactly the same pill as human amoxicillin.
The horse paste will have different additives, but probably no worse than the ones used in pills for humans. I haven't checked since I won't be using it long term, only possibly in an emergency.

 

[Doc Sandoz]

Picked up some IVM today. Walgreens had been out of it for a few days. I'm not one of those who believe the horse type is in any inferior though. The veterinary meds are often the same as human ones. For example, my fish amoxicillin is exactly the same pill as human amoxicillin.
The horse paste will have different additives, but probably no worse than the ones used in pills for humans. I haven't checked since I won't be using it long term, only possibly in an emergency.

I too got a couple syringes of Duramectin just in case. If dubious "covid" or more likely the flu comes down the pike at me, I shall proudly proclaim myself an unvaxxed horsepaster.

 

[David PS]

Notes from this video:
A comprehensive review of ivermectin reveals that it is among the safest and most well-tolerated drugs ever introduced to the market. In this episode I walk through an expert review of ivermectin by Jacques Descotes MD, PharmD, PhD which was conducted in early 2021. In here we discuss the safety, toxicity and known side effects and drug interactions, few and mild as they are. I felt this material needed to be brought out into the public to help assure we are having complete conversations founded on the latest data. The conclusion is that “ivermectin human toxicity cannot be claimed to be a serious cause for concern.”


View: https://www.youtube.com/watch?v=ATiX0-2PEr4

 

[Perry Staltic]

The two MOA that impress me the most are it's abilities to disrupt viral binding to ACE2 (antiviral) and to maintain ATP under hypoxic conditions.

The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article

https://www.nature.com/articles/s41429-021-00430-5.pdf

Nature retracted that study, most likely under pressure. Here is an active link

RETRACTED ARTICLE: The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article

www.ncbi.nlm.nih.gov

 

[Chai-jin]

I received some IVM recently from someone in the next town I met on Fb
I had some serious lung condition which I assumed was from shedding off the Fizr injection of a woman I was seeing who I sadly had to stop seeing as I thought I got a bit better but got worse after seeing her.
But I've no idea
Just have some lung condition now daily with mildly sore throat - but reluctant somehow to take IVM just on a whim unless I know I have the rona, and I didn't even have cold symptoms or loss of smell, cough or anything - but dried out and inflamed lungs which has now become chronic. Thankfully not acute.

 

[Mito]

Conclusions​

Ivermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.

Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis

COVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patien…

www.sciencedirect.com

 

[Mito]

View: https://twitter.com/pierrekory/status/1478614885466476545?s=21

 

[Doc Sandoz]

View: https://twitter.com/pierrekory/status/1478614885466476545?s=21

Surprised Kory hasn't been banned from Twit.

 

[Mito]

Ivermectin Prophylaxis Used for COVID-19: A Citywide, Prospective, Observational Study of 223,128 Subjects Using Propensity Score Matching

Background: Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related comorbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of...

www.cureus.com

 

[Mito]

Results: Of the 223,128 citizens of Itajaí considered for the study, a total of 159,561 subjects were included in the analysis: 113,845 (71.3%) regular ivermectin users and 45,716 (23.3%) non-users. Of these, 4,311 ivermectin users were infected, among which 4,197 were from the city of Itajaí (3.7% infection rate), and 3,034 non-users (from Itajaí) were infected (6.6% infection rate), with a 44% reduction in COVID-19 infection rate (risk ratio [RR], 0.56; 95% confidence interval (95% CI), 0.53-0.58; p < 0.0001). Using PSM, two cohorts of 3,034 subjects suffering from COVID-19 infection were compared. The regular use of ivermectin led to a 68% reduction in COVID-19 mortality (25 [0.8%] versus 79 [2.6%] among ivermectin non-users; RR, 0.32; 95% CI, 0.20-0.49; p < 0.0001). When adjusted for residual variables, reduction in mortality rate was 70% (RR, 0.30; 95% CI, 0.19-0.46; p < 0.0001). There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001). After adjustment for residual variables, reduction in hospitalization rate was 67% (RR, 0.33; 95% CI, 023-0.66; p < 0.0001).

Conclusion: In this large PSM study, regular use of ivermectin as a prophylactic agent was associated with significantly reduced COVID-19 infection, hospitalization, and mortality rates.

Ivermectin Prophylaxis Used for COVID-19: A Citywide, Prospective, Observational Study of 223,128 Subjects Using Propensity Score Matching

Background: Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related comorbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of...

www.cureus.com