Disruption of steroidogenesis after dimethoate exposure and efficacy of N-acetylcysteine in rats: an old drug with new approaches

Abstract

Organophosphates (OPs) like dimethoate (DMT), are pesticides used worldwide, which can affect both animals and human. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radical biosynthesis. The present study was designed to investigate the reprotoxic effects of DMT and the protective role of N-acetylcysteine (NAC) in male rat. DMT (20 mg/ kg/body weight) was administered daily to rats via gavage in corn oil and NAC (2 g/l) was added to drinking water for 30 days. Rats were sacrificed on the 30th day, 2 h after the last administration. Markers of testis injury (steroidogenesis impairment) and oxidative stress (lipid peroxidation, reduced glutathione, and antioxidant status) were assessed. In DMT-exposed rats, the serum level of testosterone was decreased. Further, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in the testis of rats during DMT intoxication. Real-time PCR (RT-PCR) analysis demonstrated a decrease in messenger RNA (mRNA) levels for testicular steroidogenic acute regulatory StAR protein, cytochrome P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β hydroxysteroid dehydrogenase (17β-HSD) in the testis after DMT exposure. No significant changes in the oxidative stress status and selected reproductive variables were observed on CTN group, whereas NAC restored the oxidative stress and the steroidogenesis on NAC group. Dimethoate induces reprotoxicity and oxidative stress. N-acetylcysteine showed therapeutic recovery effects against dimethoate toxicity.

Impacts of n‐acetyl cysteine on gibberellic acid‐induced testicular dysfunction through regulation of inflammatory cytokines, steroid and antioxidant activity

“…The picture of our study was completed by the mRNA expression findings in which it was found that gibberellic acid downregulation of both 3β‐HSD and P450scc genes that show a major role in testosterone biogenesis accompanied with significant upregulation in co‐treatment with NAC. This result was in agreement with (Jallouli et al., 2016) in which they found that supplementation of NAC reinstated steroidogenesis and safeguards Leydig cells against N, N‐Dimethyltryptamine (DMT) toxicity.…”

Antioxidant treatment ameliorates prefrontal hypomyelination and cognitive deficits in a rat model of schizophrenia

“…As high concentrations of NAC are lethal at young ages, we started with a low dose (0.9 g of NAC per liter) that has successfully been used in pups before [ 19 ]. We increased the dose during young adulthood to 2 g of NAC per liter as this dose has been used before in adult rats to reduce oxidative stress for long periods of time [ 20 ]. Using 5 M NaOH, the pH was adjusted to 8.6, equivalent to the pH of control drinking water, and NAC as well as control drinking water was offered in dark drinking bottles to prevent NAC oxidation by light.…”

“…NAC treatment APO-SUS and APO-UNSUS rats were treated between P5-P40 (±1 day) with 0.9 g of NAC (A7250 Sigma) per liter and from P40-P90 (±1 day) with 2 g of NAC per liter in the drinking water. NAC treatment regimen was based on Cabungcal et al [19] and Jallouli et al [20]. As high concentrations of NAC are lethal at young ages, we started with a low dose (0.9 g of NAC per liter) that has successfully been used in pups before [19].…”

Effects of Diethyl Phosphate, a Non-Specific Metabolite of Organophosphorus Pesticides, on Serum Lipid, Hormones, Inflammation, and Gut Microbiota

“…Previously, epidemiological studies established correlations between OPs and endocrine system diseases [8,9,10] or infertility [11,12] based on urinary measurements of DEP. The endocrine-disrupting effects of OPs, including chlorpyrifos [13,14,15,16,17,18], diazinon [19,20], malathion [21], triazophos [22], and dimethoate [23], have only been proven in animal studies, which reported a disorder of hormones involved in the hypothalamic‒pituitary‒adrenal [20], hypothalamic‒pituitary‒thyroid [14,17,18,19], and hypothalamic‒pituitary‒gonadal axes [14,15,16,17,21,22,23]. All of these OPs metabolize to DEP in vivo; however, we do not know whether these effects are induced by the parent OPs or the metabolites, especially the non-specific metabolite, DEP.…”