Mancozeb impaired male fertility in rabbits with trials of glutathione detoxification

Elsharkawy, Eman E.; El-Nasser, Mahmoud Abd; Bakheet, Aliaa A.

doi:10.1016/j.yrtph.2019.04.012

Cited by 20 publications

(14 citation statements)

References 45 publications

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“…Testicular activities of ALP, ACP G6PD, and LDH are associated with spermatogenesis and serves as testicular, and spermatogonia cell function biomarkers, and survival (Elsharkawy et al., 2019). Reduction in testicular acid phosphatase (ALP and ACP) in rats treated with TAM alone adversely affect steroidogenesis and spermatogenesis (Owumi, Ochaoga et al, 2019; Peruquetti et al., 2010), while decreases in LDH and G6PD activities could affect the pathway of lactate uptake and nicotinamide adenine dinucleotide phosphate, respectively, in spermatogenic cells utilizing these precursor materials.…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic acid co‐administration abates tamoxifen‐mediated reproductive toxicities in male rats: An experimental approach

et al. 2021

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Reports over the years have demonstrated toxic side effect-including reproductive toxicity-of tamoxifen (TAM), a drug of choice in the management of primary breast cancer. Chlorogenic acid (CGA), a dietary polyphenol, reportedly elicits beneficial pharmacological effects. However, the impact of CGA on TAM-associated reproductive toxicity is absent in the literature. We, therefore, experimented on CGA's effect and TAM-mediated reproductive toxicity in rats. Cohorts of rats were treated with TAM (50 mg/kg) or co-treated with CGA (25 or 50 mg/kg) for 14 consecutive days. The result showed that treatment of CGA significantly increases testosterone, LH, and FSH levels compared to the TAM group. However, prolactin level was markedly decreased after pretreatment of CGA in TAM-treated rats. CGA abated TAM-induced decreases acid phosphatase, alkaline phosphatase, and antioxidant enzymes in the testis. CGA alleviated TAM-facilitated surges of reactive oxygen and nitrogen species, myeloperoxidase, nitric oxide, interleukin-1β, and tumor necrosis factor-alpha in rats epididymis and testes. Additionally, CGA increased anti-inflammatory cytokine-interleukin-10-, suppressed caspase-3 activity, and reduced pathological lesions in the examined organs of rats co-treated with CGA and TAM. CGA phytoprotective effect improved reproductive function occasioned by TAM-mediated toxicities in rats, by abating oxido-inflammatory damages and downregulating apoptotic responses. Practical applications CGA protects against the damaging oxido-inflammatory responses incumbent on TAM metabolism. As an antioxidant abundant in plant-derived foods, CGA reportedly protects against inflammatory damage, hypertension, and neurodegenerative diseases. We present evidence that CGA ameliorates TAM-induced reproductive dysfunction by suppressing oxidative and inflammation stress downregulate apoptosis and improve reproductive function biomarker in rats.

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Section: Discussionmentioning

confidence: 99%

Chlorogenic acid co‐administration abates tamoxifen‐mediated reproductive toxicities in male rats: An experimental approach

et al. 2021

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“…In addition, inhibition of testicular 3βhydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase is considered to be the potential mechanism for MCZ (500 mg/kg b.w)-induced testosterone reduction (42). However, another study demonstrated an increase in testicular 3β-HSD activity in response to 100 mg/kg b.w MCZ exposure (43). Such an inconsistency may arise from distinct effects of various doses of MCZ, which should be addressed in future doseresponse studies.…”

Section: Testesmentioning

confidence: 99%

Endocrine-disrupting activity of mancozeb

Skalny¹,

Aschner²,

Paoliello³

et al. 2021

Arhiv za farmaciju

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The objective of the present study was to review the existing data on the mechanisms involved in the endocrine disrupting activity of mancozeb (MCZ) in its main targets, including thyroid and gonads, as well as other endocrine tissues that may be potentially affected by MCZ. MCZ exposure was shown to interfere with thyroid functioning through impairment of thyroid hormone synthesis due to inhibition of sodium-iodine symporter (NIS) and thyroid peroxidase (TPO) activity, as well as thyroglobulin expression. Direct thyrotoxic effect may also contribute to thyroid pathology upon MCZ exposure. Gonadal effects of MCZ involve inhibition of sex steroid synthesis due to inhibition of P450scc (CYP11A1), as well as 3b-HSD and 17b-HSD. In parallel with altered hormone synthesis, MCZ was shown to down-regulate androgen and estrogen receptor signaling. Taken together, these gonad-specific effects result in development of both male and female reproductive dysfunction. In parallel with clearly estimated targets for MCZ endocrine disturbing activity, namely thyroid and gonads, other endocrine tissues may be also involved. Specifically, the fungicide was shown to affect cortisol synthesis that may be mediated by modulation of CYP11B1 activity. Moreover, MCZ exposure was shown to interfere with PPARg signaling, being a key regulator of adipogenesis. The existing data also propose that endocrine-disrupting effects of MCZ exposure may be mediated by modulation of hypothalamus-pituitary-target axis. It is proposed that MCZ neurotoxicity may at least partially affect central mechanisms of endocrine system functioning. However, further studies are required to unravel the mechanisms of MCZ endocrine disrupting activity and overall toxicity.

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“…These substances may easily enter the food chain and drinking water, resulting in many adverse health effects even at non-lethal concentrations (Costa-Silva et al, 2018). Ethylene-bis-dithiocarbamate (EBDC) fungicides containing heavy metal atoms belong to a subclass of dithiocarbamates (DTCs) (Elsharkawy et al, 2019). Mancozeb (MZB), a complex of EBDC-Mn with zinc salt, is one of the fungicides used on a global scale and accounts for >20% of the market.…”

Section: Introductionmentioning

confidence: 99%

“…Another study in 2018 (Mohammadi-Sardoo et al, 2018) showed deleterious changes in the architecture of testis, oxidative stress imbalance, and apoptosis following MZB administration. It was also found to impair male fertility in rabbits with anti-spermatogenic and antisteroidogenic adverse effects (Elsharkawy et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of mancozeb on Sertoli–germ cell co-culture system: Role of MAPK signaling pathway

et al. 2021

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Mancozeb (MZB) is a worldwide fungicide for the management of fungal diseases in agriculture and industrial contexts. Human exposure occurs by consuming contaminated plants, drinking water, and occupational exposure. There are reports on MZB’s reprotoxicity such as testicular structure damage, sperm abnormalities, and decrease in sperm parameters (number, viability, and motility), but its molecular mechanism on apoptosis in testis remains limited. To investigate the molecular mechanisms involved in male reprotoxicity induced by MZB, we used primary cultures of mouse Sertoli–germ cells. Cells were exposed to MZB (1.5, 2.5, and 3.5 μM) for 3 h to evaluate viability by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, and oxidative stress parameters (lipid peroxidation). Cell death and mitogen-activated protein kinase (MAPK) signaling were measured in these cells using flow cytometry and western blotting. In addition, some groups were exposed to N-acetylcysteine (NAC, 5 mM) in the form of co-treatment with MZB. Mancozeb reduced viability and increased the level of intracellular ROS, p38 and c-Jun N-terminal kinases (JNK) MAPK proteins phosphorylation, and apoptotic cell death, which could be blocked by NAC as an inhibitor of oxidative stress. The present study indicated for the first time the toxic manifestations of MZB on the Sertoli–germ cell co-culture. Redox imbalance and p38 and JNK signaling pathway activation might play critical roles in MZB-induced apoptosis in the male reproductive system.

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Mancozeb impaired male fertility in rabbits with trials of glutathione detoxification

Cited by 20 publications

References 45 publications

Chlorogenic acid co‐administration abates tamoxifen‐mediated reproductive toxicities in male rats: An experimental approach

Chlorogenic acid co‐administration abates tamoxifen‐mediated reproductive toxicities in male rats: An experimental approach

Endocrine-disrupting activity of mancozeb

Cytotoxicity of mancozeb on Sertoli–germ cell co-culture system: Role of MAPK signaling pathway

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