Effects of N-Acetylcysteine Supplementation on Oxidative Stress and Expression of Apoptosis-Related Genes in Testicular Tissue of Rats Exposed to Lead.

Abstract

Lead occupational exposure is now a main concern in the modern world. Lead is a non-biodegradable element with multi-devastating effects on different organs. Acute or chronic exposure to lead is reported to be one of the most important causes of infertility both in males and females basically by inducing oxidative stress and apoptosis. The current study scrutinized the mitigating effects of N-acetylcysteine (NAC) on lead toxicity, oxidative stress, and apoptotic/anti-apoptotic genes in the testis tissues of male rats. Rats were randomly divided into a control group (G1) and four study groups treated with single and continuous doses of lead with and without NAC administration. Malondialdehyde (MDA), total antioxidant capacity (TAC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were analyzed as oxidative stress biomarkers and the expression of apoptosis-related genes was studied using RT-PCR. Continuous exposure to lead caused a significant decrease in sperm count, motility, viability, and morphology (P < 0.001). Number of germinal cells, Leydig cells, spermatocytes, and the diameter of seminiferous tubule were significantly decreased (P < 0.001) in G3 group. Continuous exposure to lead significantly decreased TAC content, but increased the levels of MDA and 8-OHdG (P < 0.001). Administration of continuous dose of lead dramatically increased expression of Bax, Caspase-3, Caspase-8, Cytochrome-C, MMP2, and MMP9 genes in testicular tissue. NAC treatments not only improved morphological changes and sperm quality, but also enhanced antioxidant balance and modulated apoptosis process in testicular tissue of rats. Lead exposure strongly motivated testicular cells towards apoptosis, caused an oxidant/antioxidant imbalance, and decreased sperm quality along with morphological changes in testis cells. NAC treatments was associated with protective effects on testicular tissue mainly by rebalancing of the antioxidants capacity, as well as downregulation of apoptosis-related genes.