Reproductive toxicity of methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) in male wistar rats

Barnes, Tyler; Verlangieri, Anthony J.; Wilson, Marvin C.

doi:10.1016/0300-483x(83)90110-5

Cited by 37 publications

(3 citation statements)

References 22 publications

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“…Analogs of albendazole, benomyl and carbendazim, have been used to control microsporidia in insects such as Nosema heliothidis in Heliothis zea and Nosema kingi in Drosophila willistoni (Wei et al, 2022, Armstrong, 1976, Brooks et al, 1978. However, microsporidiosis in mammals cannot be treated with benomyl and carbendazim because of their hepatotoxicity and toxic effects on reproduction (Sakr et al, 2004, Barnes et al, 1983 (Kotková et al, 2017). Since benzimidazoles have been widely used for decades, resistance fears have arisen.…”

Section: Introductionmentioning

confidence: 99%

Screening of the Pandemic Response Box identifies anti-microsporidia compounds

Huang,

Chen,

Pan

et al. 2023

Preprint

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Microsporidia are fungi-like obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors, we took advantage of the model organism Caenorhabditis elegans infected with its natural microsporidian Nematocida parisii. We used this system to screen the Pandemic Response Box, a collection of 400 diverse compounds with known antimicrobial activity. After testing these compounds in a 96-well format at high (100 μM) and low (40 μM) concentrations, we identified four inhibitors that restored the ability of C. elegans to produce progeny in the presence of N. parisii. All four compounds reduced the pathogen load of both N. parisii and Pancytospora epiphaga, a C. elegans-infecting microsporidia related to human-infecting species. One of these compounds, a known inhibitor of a viral protease, MMV1006203, inhibited invasion and prevented the firing of spores. An albendazole analog, MMV1782387, inhibited proliferation of N. parisii. We tested albendazole as well as 5 other analogs and observed that MMV1782387 was amongst the strongest inhibitors of N. parisii and displayed the least host toxicity. Our study further demonstrates the effectiveness of the C. elegans-N. parisii system for discovering microsporidia inhibitors and the compounds we identified provide potential scaffolds for anti-microsporidia drug development.

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Section: Introductionmentioning

confidence: 99%

Screening of the Pandemic Response Box identifies anti-microsporidia compounds

Huang,

Chen,

Pan

et al. 2023

Preprint

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show abstract

“…Analogs of albendazole, benomyl, and carbendazim have been used to control microsporidia in insects such as Nosema heliothidis in Heliothis zea and Nosema kingi in Drosophila willistoni [16,23,24]. However, microsporidiosis in mammals cannot be treated with benomyl and carbendazim because of their hepatotoxicity and toxic effects on reproduction [25][26][27]. Since benzimidazoles have been widely used for decades, resistance fears have arisen.…”

Section: Introductionmentioning

confidence: 99%

Screening of the Pandemic Response Box identifies anti-microsporidia compounds

Huang,

Chen,

Pan

et al. 2023

PLoS Negl Trop Dis

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Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors, we took advantage of the model organism Caenorhabditis elegans infected with its natural microsporidian Nematocida parisii. We used this system to screen the Pandemic Response Box, a collection of 400 diverse compounds with known antimicrobial activity. After testing these compounds in a 96-well format at high (100 μM) and low (40 μM) concentrations, we identified four inhibitors that restored the ability of C. elegans to produce progeny in the presence of N. parisii. All four compounds reduced the pathogen load of both N. parisii and Pancytospora epiphaga, a C. elegans-infecting microsporidia related to human-infecting species. One of these compounds, a known inhibitor of a viral protease, MMV1006203, inhibited invasion and prevented the firing of spores. A bis-indole derivative, MMV1593539, decreased spore viability. An albendazole analog, MMV1782387, inhibited proliferation of N. parisii. We tested albendazole as well as 5 other analogs and observed that MMV1782387 was amongst the strongest inhibitors of N. parisii and displayed the least host toxicity. Our study further demonstrates the effectiveness of the C. elegans-N. parisii system for discovering microsporidia inhibitors and the compounds we identified provide potential scaffolds for anti-microsporidia drug development.

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“…In the natural environment as well as in biological systems, beno is predominantly metabolized to carbendazim (methy-2-benzimidazole carbamate) [15][16][17][18]. Both beno and carbendazim are fungicidal through the inhibition of microtubule assembly by the tubulins [19,20]. Beno is also known to cause adverse effects on the male reproductive system, including decreased testicular and epididymis weights, and reduced epididymis sperm counts and fertility in rats [21,22].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Sasaya¹,

Yasuzumi²,

Maruoka³

et al. 2012

ABC

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Endocrine-disrupting chemicals (EDCs) are known to exert estrogen-like effects that are similar to those made by naturally produced hormones or by inhibition of the receptors in the cell receiving the hormones. Recently, several reports have indicated that EDCs can affect the developing central nervous system. In our current study, we report that some EDCs induce apoptosis in cultured PC12 cells and can be classified into three groups. Bisphenol A (BPA), pnonylphenol (NP) and tributyltin chloride (TBT) were found to induce endoplasmic reticulum (ER) stress-associated apoptosis and activate the unfolded protein response (UPR) system, whereas benomyl (beno) induced non-ER stress-associated apoptosis. The half-maximal apoptosis-inducing concentrations (IC 50 ) of these EDCs were 160 µM for BPA, 25.6 µM for NP, 640 nM for TBT and 48 µM for beno. Although these concentrations are higher than those found in the environment, some EDCs may have apoptotic effects on various cells in the body, including neurons, through their accumulation in the body over time or condensation through the food chain. On the other hand, benzopyrene, fenvalerate, styrene monomer and bis(2-ethylhexyl)phthalate did not induce apoptosis in PC12 cells. We analyzed also whether apoptosis-inducing EDCs had an estrogen-like effect on cultured PC12 cells transfected with a luciferase reporter plasmid, the activity of which is dependent on estrogen receptor α. We found that BPA had an estrogen-like effect (EC 50 = 5.9 µM) but that NP, TBT and beno did not in transfected PC12 cells. These results suggest that BPA may predominantly exert estrogenic effects, but others may predominantly have apoptosis-inducing effects on cells in the body exposed to a polluted environment.

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Reproductive toxicity of methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) in male wistar rats

Cited by 37 publications

References 22 publications

Screening of the Pandemic Response Box identifies anti-microsporidia compounds

Screening of the Pandemic Response Box identifies anti-microsporidia compounds

Screening of the Pandemic Response Box identifies anti-microsporidia compounds

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

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