Inhibition of catalase activity with 3-amino-1,2,4-triazole intensifies bisphenol A (BPA)-induced toxicity in granulosa cells of female albino rats

Exposure to bisphenol A (BPA), an endocrine disruptor and environmental toxicant, is associated with adverse estrogenic effects in both humans and wildlife species. Because the effects of BPA on the ovary at the cellular level are incompletely understood, the present study was designed to investigate the underlying mechanism of granulosa cell injury following BPA exposure. Eight-week-old female Wistar rats were treated with BPA (25 mg/kg BW/day for 9 days, intraperitonially) with or without pretreatment of the catalase-specific blocker 3-amino-1,2,4-triazole (ATZ; 1 g/kg BW/day for 5 days, intraperitonially). Different oxidative and antioxidant stress parameters, pro-inflammatory cytokines, and hormonal levels were measured. Catalase expression in isolated granulosa cells was analyzed by Western blot. There were noticeable increases in both nitric oxide and lipid peroxidation levels in the granulosa cells of the BPA-treated group with or without pretreatment with ATZ. Compared with the controls, BPA exposure resulted in a significant increase in pro-inflammatory cytokine levels that was further increased following pretreatment with ATZ. Results of the hormonal assays clearly showed a significant decrease in both estrogen and progesterone levels. In contrast, there was a significant increase in both serum follicle-stimulating hormone and luteinizing hormone levels following BPA exposure, with or without ATZ pretreatment. Results of Western blot analysis demonstrated decreased expression of catalase in the BPA-treated group and a further decrease in expression in the group treated with both BPA and ATZ. Our data suggest that catalase plays a role in mediating reproductive damage to granulosa cells exposed to BPA.