"CLASTOGENIC" - 18 Studies Highlighting Ivermectin Induced DNA Breakage, Damage & Related Disorders
Cytotoxic, Mutagenic, Genotoxic & Clastogenic? Ivermectin Is A Menace
Definitions:
A clastogen is a substance or agent that induces chromosomal breakage or structural changes in the DNA of cells. The term "clastogen" is derived from the Greek word "klastos," meaning "to break." Clastogens can cause damage to the genetic material, leading to the formation of chromosomal aberrations.
A mutagen is a substance or agent that can induce changes or mutations in the DNA sequence of an organism. These mutations can alter the genetic information and potentially lead to the development of new diseases.
Genotoxic refers to substances or agents that have the ability to damage or alter the genetic material (DNA) of living cells, increasing the risk of mutations. These mutations can have detrimental effects on the organism, potentially leading to the development of cancer or other genetic disorders.
In this article I want to look at a number of studies showing a dose dependent increase in DNA breaks, chromosomal aberrations, etc when ivermectin is administered to cell cultures or animals.
Video report now available: https://rumble.com/v2yp1we-ivermectin-dna-wreckage-depopulation-agent-ivm-is-mutagenic-genotoxic-and-c.html
Study #1: Mutagenicity of Ivermectin In Rats
In a study titled ‘The mutagenic effects of ivermectin in germinal cells and serum
protein of the mouse’ by Sweify et al, researchers conducted an experiment to investigate the mutagenicity of Ivermectin on meiotic chromosomes of mice. They found a significant increase in meiotic aberrations, suggesting that Ivermectin is of mutagenic nature. (full report)
“Effects of ivermectin on spermatocyte chromosomes: Structural aberrations: Cytological analysis of diakinesis-metaphase I spermatocytes of the treated samples revealed significant increase in chromosome aberrations over the control values.”
“Analysis of the treated samples revealed significant increase in meiotic aberrations, 33.83% vs 5.8% for the control (P < 0.001)… These findings supports the mutagenicity of IVM”
“Effects of ivermectin on spermatocyte chromosomes: … spermatocytes of the treated samples revealed significant increase in chromosome aberrations over the control values”
“The present observations pointed to the mutagenic effects of IVM. The frequency of translocation is significantly higher than that found in the control samples”
“These studies revealed high clastogenic and genotoxic potential of IVM”
“In the present work, IVM induced significant increase in the reciprocal translocation figs.of primary spermatocytes. The changes in the serum protein fractions add another warning for the mutagenicity of IVM.”
Study #2: Ivermectin Genotoxicity On Buffalo Lymphocytes
In a paper called ‘Antimutagenic Activity of Some Natural supplements on Ivermectin genotoxicity in Lymphocytes of Buffalo’ by El-makawy et al, researchers investigated the impact of garlic, L-carnitine, and wheat germ oil on the genotoxicity induced by ivermectin in buffalo lymphocyte cultures, finding that ivermectin caused a significant rise in micronuclei and chromosomal aberrations with increasing doses (full report)
Cell Abnormalities
Structural Chromosomal Aberrations Observed:
“Results showed that ivermectin induced dose dependent increase in the frequencies of the binucleated lymphocytes with micronuclei as well as the number of micronuclei in lymphocytes of river buffalo”
“Ivermectin low dose caused non-significant increase in the frequency of total chromosomal aberrations in lymphocytes of river buffalo as compared to control. Whereas, in medium and high doses the frequencies of aberrant cells increased at a significant level (P ≤ 0.001) than control.”
“In addition, the numbers of binucleated lymphocytes showed dose dependent decrease than control. These results revealed that the drug has a cytotoxic effect on the number of cell divisions. As the micronuclei are small chromatin-containing bodies arising from chromosome fragmentation by breaks or deletion, the results of MN [micronuclei] formation confirmed our results of chromosomal aberrations indicating the clastogenic effects of ivermectin.”
Study #3: Ivermectin’s Cytogenic Potential On Mice Bone Marrow Cells
In a study called ‘The cytogenetic potential of ivermectin on bone marrow cells of
mice in vivo’ from Sweify et al, researchers evaluated the cytogenicity of Ivermectin (IVM) on mice through chromosomal aberration and micronucleus tests, finding that IVM induced high levels of chromosome aberrations and genotoxicity in somatic cells.
“IVM induced high level of chromosome aberrations in somatic cells, as it is ascertained by chromosome aberration assay and micronuclei production in bone marrow cells. This study revealed high clastogenic and genotoxic potential of IVM on mice”
“The Table contains also the different types of chromosomal aberrations recorded in the examined cells. A single i.p. injection of ivermectin [200μg/kg ivermectin] resulted in a significant (P≤0.001) increase in percentage of aberrant cells”
“It is clear from the Table (II) that injection with ivermectin induced high significant increase in the frequency of the damaged cells allover the examined periods (P≤0.001).”
Study #4: Ivermectin Breaks DNA Strands In Chinese Hamster Ovary Cells
In a study called ‘In vitro genotoxic and cytotoxic effects of ivermectin… on Chinese hamster ovary (CHO K1 ) cells’ by Molinari et all, researchers conducted various genotoxicity and cytotoxicity assays to investigate the effects of ivermectin (IVM) and its commercial formulation ivomec® on Chinese hamster ovary (CHO K1) cells and found that Ivermectin caused DNA-strand breaks in Chinese hamster ovary cells. (Full article)
“… IVM and ivomec® … induced DNA-strand breaks revealed by SCGE [single
cell gel electrophoresis]”
“Both chemicals induced DNA-strand breaks revealed by the comet assay”
“IVM and ivomec® exert both genotoxicity and cytotoxicity in mammalian cells in vitro, at least in CHO K1 cells.”
“A brief 80 min pulse-treatment of 5.0–50.0 μg/ml of IVM or 25.0 and 50.0 μg/ml of ivomec® , resulted in a manifest level of single DNA-strand break induction.”
Study #5: Ivermectin Induces DNA Damage In Human HeLa Cells
In a study called ‘Ivermectin Confers Its Cytotoxic Effects by Inducing AMPK/mTOR-mediated Autophagy and DNA2 Damage’ Zhang Et Al (full writeup here)
“The results indicate that IVM can induce DNA double-strand breaks in HeLa cells, and the degree of double-strand break is dependent on the concentration of IVM.”
“Ivermectin has significant ability to induce DNA oxidative damage and enhance autophagy in HeLa cells”
“As expected, we found that IVM can induce oxidative double-stranded damage in HeLa cells, indicating that IVM has potential genotoxicity to human health.”
“We conclude that IVM produces genotoxicity and cytotoxicity by inducing DNA damage and AMPK/mTOR-mediated autophagy, thereby posing a potential risk to human health.”
Study #6: Genotoxicity and Carcinogenicity of Ivermectin On Fruit Flies
In a study called ‘Genotoxicity and carcinogenicity of ivermectin and amoxicillin in vivo systems’ by Aparecida de Sousa et al (full report here),
“The results revealed that IVM increased the frequency of epithelial tumor in D. melanogaster considering all evaluated concentrations”
“It was observed a dose-dependence in the frequency of MN [Micronuclei] in T. pallida considering the highest concentrations (11.42, 22.84 and 45.68 × 10−5 mM) differing statistically (p ≤ 0.05) from the negative control, evidencing a genotoxic effect of IVM”
“The results observed in D. melanogaster and T. pallida showed that IVM can increase the damage in the genetic material, leading to genetic instability.”
“Findings showed an increase in the frequency of micronuclei in T. pallida
treated with 11.42, 22.84 and 45.68 x 10 −5 mM of IVM. We conclude that chronic exposure to IVM is directly associated with events resulting from genetic instability (genotoxicity and carcinogenicity).”
Study #7: DNA Strand Breaks Induced By Ivermectin In Mosquitoes
In a study called ‘Genotoxic and cytotoxic in vitro evaluation of ivermectin… on Aedes albopictus larvae (CCL-126™) cells’ (Full paper):
“IVM… induced DNA-strand breaks enhancing both slightly damaged and damaged cells at 25–50 μg/ml IVM”
“Data indicated that IVM exerts both genotoxicity and cytotoxicity in insect cells [A. albopictus larvae CCL-126 cells] in vitro”
Study #8: High Levels Of DNA Damage In Cows Exposed To Ivermectin
In a paper called ‘Comet assay to determine genetic damage by the use of ivermectin in zebu cows’ by Montes-Vergara et al, researchers explored how much DNA damage ivermectin causes in the Zebu cow.
“The values of classification of comets indicate cells with high levels of damage (grade 3: cells with high damage). The rate of DNA damage of the treatment to 1% to 3.15% was significant… The results obtained in this study demonstrate the likely genotoxic potential of the use of IVM in cattle.”
“Regardless of the IVM concentration, the presence of nuclei with DNA migration (Figure 1a and b) was observed at a percentage greater than 75% in all cells observed per plaque, demonstrating the ability of the IVM compound to produce simple chain breaks in the DNA molecule.”
The Comet classification describes how damaged the DNA of cells are. All of the control group (no treatment) measured 0 on the comet scale, indicating little if any DNA damage. Here are the comet classification results for the IVM treated cows:
“The results found in the present study constitute concrete evidence for the induction of genomic damage as exerted by IVM, using the comet assay methodology”
“In conclusion, the results suggest that the genetic damage found in the studied livestock may be associated with the use of IVM”
Study #9: Ivermectin’s Genotoxic Effects On Tadpoles
In a study called ‘Genotoxicity of Three Avermectins on Polypedates megacephalus Tadpoles Using the Comet Assay’ by Geng et al, some very concerning findings were noted in relation to Ivermectin’s “genotoxic effects at relatively low concentrations” in Tadpoles. (Full Paper)
“The tadpoles exposed to the lower concentrations of ABM (0.006 mg/ L) showed a significant increase in DNA damage (P < 0.05), and the tadpoles exposed to other concentrations of the three avermectins showed a highly significant increase in DNA damage (P < 0.01)”
“Our results showed clearly that avermectins caused dose dependent DNA damage on amphibian tadpoles… The three avermectins increased the DNA damage observed in the tadpoles in a dose-responsive manner. There were strong linear correlations between the DNA damages and the concentrations of the three test substances (Figure 2). The cellular distributions of DNA damages in tadpoles are shown in Figure 3. Of the tadpoles treated with increasing concentrations of the three test substances, higher proportions of cells had greater amount of DNA damage than those of the negative control”
This chart shows a dose-dependent increase in DNA damage as IVM dosing increases:
“According to these results above and our finding that avermectins can cause DNA damage in tadpoles at the concentrations below the recommended applied levels (Xu et al., 2010), we consider it possible that avermectins are carcinogenic, and confirm it has the negative impact on the development of tadpoles”
Study #10: Ivermectin Induced DNA Damage In Chinese Hamster Ovary Cells
In a paper called ‘DNA damage kinetics and apoptosis in ivermectin-treated chinese hamster ovary cells’ (full report) by Molinari et al, researchers conducted an experiment using the comet assay to analyze the kinetics of DNA damage in Chinese hamster ovary cells induced by ivermectin.
“After 6 h of treatment, cell survival decreased up to 75% and 79% in IVM- and IVO-treated cultures, respectively”
“A clear increase in DNA damage was found immediately after
test compound treatments (0 h) (Fig. 1). In both IVM- (Fig. 1A) and IVO-treated cells (Fig. 1B)”
“For both anthelmintics, biphasic behavior in DNA damage occurred during the incubation time.”
A time-dependent increase of IVM- and IVO-induced DNA damage was observed within 0 to 3 h after pulse treatment, revealed by a progressive decrease of undamaged cells and an increase in slightly damaged and damaged cells.”
“A time-dependent increase in IVM- and IVO-induced DNA damage was observed by a progressive decrease of undamaged cells simultaneously with an increase in the frequency of slightly damaged and damaged cells within the 0–3 h post-incubation time. “
Study #11: Avermectin Induces DNA Damage In Chinese Mitten Crab Haemocyte Blood Cells
In a paper called ‘Avermectin induces the oxidative stress, genotoxicity, and immunological responses in the Chinese Mitten Crab, Eriocheir sinensis’ researchers investigated the aquatic toxicity of avermectin and its effects on E. sinensis crabs. The study found that exposure to sublethal concentrations of avermectin resulted in decreased levels of antioxidants, increased oxidative products, elevated levels of reactive oxygen species (ROS), reduced phagocytic activity, and genetic damage in the crabs, indicating significant toxic effects on the species including oxidative stress, immunological activity inhibition, and genotoxicity.
“Avermectin or its family members can induce oxidative and immunological dam-
age as well as genotoxicity in mammals, birds and fish”“the 48-h and 96-h LC50 values of avermectin on E. sinensis were 1.663 mg/ L … and 0.954 mg/L”
“Avermectin induces DNA damage in haemocytes”
“a comet assay was performed to investigate the level of DNA damage under avermectin exposure. In control, most haemocytes were observed with a circular, intact nuclei, whereas different degree of comets in the exposure groups early at 24 h. More comets appeared with increase of avermectin concentration. The comet ratio and percentage of DNA in tail increased significantly at each concentration from 24 h (P< 0.05). In group of 0.48 mg/ L, the comet ratio and percentage of DNA rose about 2.7 and 4.1 fold respectively, in comparison to control at 24 h. Although there was a slight recovery at 48 or 72 h, it continued to increase at 96 h. Even in group of 0.03 mg/L, the values of both comet ratio and percentage of DNA are 3.8 and 5.0 fold higher than control at 96 h.”
“Avermectin induces MN [Micronuclei] frequency in haemocytes… An obvious increase of MN frequency was observed at high concentrations especially at 0.48 mg/L from 48h exposure. And at 96 h, there is a significant difference in concentration groups of 0.12, 0.24 and 0.48 mg/L compared to control (P< 0.05)”
“According to the results from two-way ANOVA, a significant interaction between avermectin concentration and exposure time was found for all biomarkers involved (Table 1). All biomarkers investigated in this test showed a significant correlation between the concentration, exposure time and their cross combination. It indicated that both avermectin concentrations and exposure time have significant effects on the oxidative, immunological response and DNA damage in E.sinensis”
“The MN test was developed as a simple and practical in vivo cytogenetic screening method for mutagens [42]. In the present study, MN frequency increased significantly in high concentration groups from 48 h”
Study #12: Ivermectin’s Genotoxic Effects In White Swiss Mice Bone Marrow
In a paper called ‘The Study of Genotoxic and Cytotoxic Effects and DNA Damage by Ivermectin in Bone Marrow of Male White Swiss Mice Mus musculus’ by Sadek et al, researchers evaluated the genotoxic and cytotoxic effects of Ivermectin (IVM) on the bone marrow of male white Swiss mice using various cytogenetic endpoints. The results demonstrated that IVM administration led to a significant decrease in polychromatic erythrocytes and a significant increase in micronuclei formation, indicating both anuegenic and clastogenic effects. Furthermore, the comet assay revealed significant DNA damage in bone marrow cells treated with IVM, highlighting its genotoxic and cytotoxic potential in somatic cells.
“Results of current study revealed that IVM have genotoxic and cytotoxic effects on somatic cells of male white mice.”
“Oral treatment of white mice with IVM induced a significant DNA damage in bone marrow cells, which revealed by comet assay results, the mean of damaged bone marrow cells in mice treated with doses 0.6 and 0.8 mg/ kg. b.wt. were different significantly when compared with negative control(P≤ 0.01).”
“IVM induced both anuegenic and clastogenic effects in bone marrow of male white mice, The results showed a significant increase in means of numerical chromosome aberrations (anueploidy and polyploidy) (P≤ 0.05), the highest mean of structural chromosome aberration (with and without gabs) was recorded in mice treated with 0.8 mg/ kg. b.wt. (P≤ 0.01).”
“The results showed that IVM induced significant decrease in the mean of polychromatic erythrocytes and the lowest value was recorded at the dose 0.6 mg/ kg. b.wt.(P≤ 0.01) and significant increase in the mean of micronuclei were induced by the three doses of drug (P≤ 0.01).”
Study #13: Ivermectin’s Mutagenic Effects in Mice
In a paper called ‘Mutagenic Effects of the Combination and Its Components of Albendazole and Ivermectin in vivo and in vitro’ by Lin et al
“Albendazole and ivermectin, common antiparasitic drugs widely used in livestock production, showed mutagenic effects in some extent”
“the mice treated with ivermectin or albendazole showed higher micronucleus frequency and sperm abnormality rate.”
“The sperm abnormalities in the ivermectin single-drug group were mainly head deformities and body-tail folds… Among them, the proportion of banana head and amorphism was the highest.”
Study #14: Ivermectin’s Genotoxicity Measured In Rat Bone Marrow Cells
In a paper called ‘In vivo combined treatment of rats with ivermectin and aged garlic extract attenuates ivermectin-induced cytogenotoxicity in bone marrow cells’ by Khalil et al (full paper), Male Sprague Dawley rats were administered varying doses of IVM intraperitoneally, and the results indicated that high doses of IVM caused significant cytogenetic toxicity.
“IVM was found cytotoxic and mutagenic at high doses since it significantly reduced %MI [mitotic index] and increased %NA [percentage nuclear abnormalities] and %Abc [percentage chromosomal abnormalities]. These observations may be due to disturbances in the mitotic processes that lead to formation of severe CA [chromosomal aberrations] and in turn caused cell death or cease of further cell divisions.”
Study #15: Studying The Pairing Of Ivermectin With Pgp Inhibitor Verapamil
In a study called ‘Effect of ivermectin on male fertility and its interaction with P-glycoprotein inhibitor (verapamil) in rats’ by El-Nahas & El-Ashmawy (full report)
Ivermectin, along with a Pgp-inhibitor/ CYP3A4-inhibitor, results in a remarkable 59% increase in abnormal sperm count, while sperm motility decreases by 8% with Ivermectin alone and by 23% when combined with the Pgp-inhibitor.
Let’s look at the differences in abnormal sperm cells by category by treatment group in this series of 9 charts:
Study #16: Ivermectin Mutagenicity Rat Study
In a paper called ‘Micronuclei induction by some anthelmintic drugs in male mice’ by EL-makawy (full report)
“Contrariwise, at 72 hrs after treatment.. ivermectin induced statistically significant increase in the number of MN [Micronuclei] over the negative control”
The researchers are concerned that the veterinary dosing of livestock may pose a potential risk of dangerous exposure, which could lead to harmful "genotoxic effects on humans."
MNPCEs stands for Micronucleated Polychromatic Erythrocytes. They are a type of abnormal cells that can be observed in the bone marrow and peripheral blood of animals, including humans, following exposure to certain genotoxic substances or conditions.
The presence of micronucleated polychromatic erythrocytes is generally considered a sign of genetic damage or chromosomal abnormalities. These cells have small additional nuclei, known as micronuclei, which contain fragments of chromosomes or whole chromosomes that were not properly incorporated into the daughter cells during cell division.
Study #17: Ivermectin Damaging DNA In Chinese Hamster Ovary & Insect Cell Lines
In a paper called ‘IVERMECTINAS: EVALUACIÓN DE SU EFECTO DELETÉREO
MEDIANTE ENSAYOS DE GENOTOXICIDAD’
“when the comet assay was employed, both ivermectin and Ivomec® were able to induce DNA single-strand breaks in CHO-K1 and CCL-126 cells”
“Overall, the results evidence that ivermectin present a similar pattern of cytotoxic and genotoxic damage than that induced by Ivomec®.”
“Our results demonstrate that ivermectin has the ability to induce damage in the DNA molecule, at least in CHO-K1 and CCL-126 cells, but also highlight a highly cytotoxic capacity as the major deleterious effect of this antibiotic.”
“Its widespread use would seriously jeopardize the organisms that are usually treated with ivermectin including human beings.”
“DNA migration analysis was performed by measuring the length and width of the observed images. All the concentrations of both compounds tested on CHO-K1 and CCL-126 cells significantly increased the levels of DNA damage.”
“The ability to induce repair introduced DNA lesions was tested in CHO-K1 and CCL-126 cells previously exposed to 50 μg/ml ivermectin and Ivomec during a 80-min treatment pulse… Immediately after treatment with both ivermectin and Ivomect (0h) a significant increase in damaged DNA was observed in a high percentage of the cell population in both cell lines”
“The deleterious capacity exerted by both compounds was reflected in the induction of single chain breaks in the DNA from cell lines used.”
Study #18: Abnormal Sperm Rates Skyrocket In Nigerian Ivermectin Users
In a study from Nigeria entitled ‘Effects of Ivermectin therapy on the sperm functions of Nigerian onchocerciasis patients’, some very concerning findings were published.
“We observed significant reduction in the sperm counts and sperm motility of the patients tested. On the morphology there was significant increase in the number of abnormal sperm cells. This took the forms of two heads, double tails, white (albino) sperms and extraordinarily large heads. It is suspected that the above alterations in the already determined parameters of the patients’ sperm cells could only
have occurred as a result of their treatment with ivermectin.”
“Sperm with abnormal morphology were also found to have increased after ivermectin therapy”
Here is a scatter plot of the % of sperm deemed “abnormal” before (x axis) and after (y axis) the ivermectin dosing. Points above the line indicate a higher % of abnormal sperm after the Ivermectin and points below the line indicate a lower % of abnormal sperm after Ivermectin.
“There was a significant drop in the sperm counts of the patients after their treatment with ivermectin.”
We can calculate the total motile count of each patient’s sample by multiplying the number of sperm in the sample times the percentage that were swimming properly.
O’Conner Ivermectin Rat Carcinogenicity Study
In an article called ‘Increased Pathology Incidence in the Forestomach of Rats Maintained on a Diet Containing Ivermectin and Given a Single Dose of N-Methyl-N1-Nitro-N-Nitrosoguanidine’ by O’Conner et al, they observed additional cancers in mice with a small amount (2 ppm) of ivermectin in their diet given a dose of a carcinogen called N-Methyl-N1-Nitro-N-Nitrosoguanidine. From the abstract:
“No tumors or pathological lesions were observed in the forestomach of the control animals or those given ivermectin alone. However, compared to animals receiving MNNG alone, rats maintained on a diet containing ivermectin (2 ppm) and given MNNG… showed an increased number of neoplasms (9/26 vs 3/18; p = 0.30) and a statistically significant fourfold increase in the number of pathological lesions (18/26 vs 3/18; p = 0.002), which include preneoplasia in the forestomach. In all cases, the pathological lesions were more severe in the animals receiving ivermectin and MNNG, compared to those receiving MNNG alone.”
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