N‐Acetyl‐cysteine mediated inhibition of spermatogonial cells apoptosis against malathion exposure in testicular tissue

Abstract

Toxicological studies so far suggest that excessive use of malathion, an organophosphate insecticide, causes serious ill-effects in mammalian reproductive physiology. The present study aims at assessing malathion-induced toxicity in a dose- and time-dependent manner with mitigating effects of N-acetyl-l-cysteine. The testicular germ cell viability was monitored using MTT assay, where NAC, being an antioxidant significantly reduced malathion-induced toxicity by enhancing the frequency of cell viability. The histomorphological analysis showed that NAC successfully diminished several apoptotic features in testicular cells, induced by malathion. The differential EB/AO staining revealed a significant decline in the percentage of apoptosis after NAC supplementation. NAC also diminished the malathion-induced DNA fragmentation along with significantly reduction in oxidative stress parameters causing decrease in lipid peroxidation and enhancement of ferric reducing antioxidant power within testicular germ cells. Thus, NAC mitigated the malathion-induced toxicity, proving its potential in infertility treatment.

Organophosphate toxicity: updates of malathion potential toxic effects in mammals and potential treatments

“…Many other in vivo and in vitro studies in animals supported the oxidative stress theory (Moridi et al 2018;Arab et al 2018); MAL-induced oxidative stress was also recently observed in many types of human cells (Durak et al 2009;Tuzcu et al 2014;Yan et al 2019;Shieh et al 2019). They found that MAL treatment leads to enhanced production of reactive oxygen species (ROS) and subsequent lipid peroxidation (Durak et al 2009;Bhardwaj et al 2018). It is evident that lipid peroxidation is accompanied by an alteration, either inhibition or activation, of the antioxidant defense system in different organs (Flehi-Slim et al 2015).…”

“…Histopathologically, MAL induced degenerative changes, necrosis, and edema in the interstitial tissues and seminiferous tubules (Uzun et al 2009). In vitro effects of MAL treatment, using spermatogonial cells, showed a significant reduction of testicular germ cells viability, with histopathological changes like pyknosis, vacuolization, empty spaces, tubular degeneration, and condensed or fragmented chromatin (Bhardwaj et al 2018). Biochemical tests were also affected, showing a significant decrease in testicular content of glycogen and sialic acid, in addition to a significant increase in testicular protein and cholesterol.…”

“…Among mostly used pesticides, MAL is ranked fourth in targeting the nervous system (Bhardwaj et al 2018). Manuscripts reported that it may have neurotoxic effects in both animals and humans that include a wide variety of neuromotoric, cholinergic, affective, and cognitive disorders, in addition to impairment of memory and discrimination (Komori et al 1991;Abdel-Rahman et al 2004;Brocardo et al 2005;dos Santos et al 2016).…”

“…The effect of MAL on the male reproductive system may be explained in terms of MAL capacity to induce an oxidative stress condition, by enhancing ROS production and lipid peroxidation, and reducing ferric reducing antioxidant power (FRAP) activity within testicular tissue (Bhardwaj et al 2018). ROS may induce DNA damage and activates apoptotic pathways.…”

“…However, they are not totally beneficial; they are important sources of environmental pollution and exert adverse health consequences, some of which are irreversible (LaVerda et al 2015;Navarrete-Meneses et al 2017). Pesticides induce both acute and chronic toxic effects including neurological manifestations, respiratory diseases, genetic damage, and reproductive disorders in various organisms (Bhardwaj and Saraf 2014;Bhardwaj et al 2018).…”