Protective role of N-Acetyl L-Cysteine against reproductive toxicity due to interaction of lead and cadmium in male Wistar rats

INTRODUCTION: One of the target organs of heavy metals is testis and many authors proposed that oxidative stress could be responsible to induce their toxicity. An experimental study was conducted to evaluate the molecular mechanisms of lead (Pb) and cadmium (Cd) toxicity, their toxicodynamic interaction and to evaluate therapeutic potential of N-Acetyl L-cysteine (NAC) against the reproductive toxicity in male Wistar rats. MATERIAL AND METHODS: rats were randomly divided into 8 groups comprising of 6 rats in each. Group 1 and 2 were syam and NAC control, Group 3, 4 and 5 were kept as toxic control groups such as lead, cadmium and lead + cadmium respectively, where as Group 6, 7 and 8 were therapeutic groups with NAC. The experiment scheduled for 3 months. Body weights, anti-oxidant profile (GSH, GST, TBARS and protein carbonyls) in testis, testis weight, testicular LDH, sperm count and histopathology were conducted. And also, interaction of Pb and Cd with zinc (Zn) and copper (Cu) in testis was assessed. RESULTS: The present study revealed significant alterations in body weights, anti-oxidant profile, weights of testes, testicular LDH, sperm count, and concentration of Zn and Cu in toxic control groups 3, 4 and 5 as compared to control and NAC-treated groups. The toxic combination (Pb+Cd) group 5 showed significant alterations in protein carbonyls, GST levels and testicular LDH as compared to Pb and Cd alone administered groups and these results are substantiated with marked changes in the histopathology. All the NAC-treated groups revealed significant improvement in all the parameters. CONCLUSION: The results of the investigation revealed that Pb, Cd and their combination induces toxicity to the biological system due to the excess generation of free radicals and impairment of anti-oxidant defenses. Toxic effects were more pronounced in the group that received a combination of Pb and Cd, suggesting positive toxicodynamic interaction. Use of NAC countered the adverse effects of Pb and Cd induced toxicity to a major extent suggesting its anti-oxidant potential owing to replenishment of tissue pool of GSH. Further, NAC administration reduced the extent of accumulation of Pb and Cd in various tissues.