Bisphenol A enhances apoptosis, fibrosis, and biochemical fluctuations in the liver of adult male rats with possible regression after recovery.

Bisphenol A (BPA) is an environmental contaminant that might be harmful. Human exposure to BPA can occur during the fetal and postnatal periods and extends throughout life. This study aimed to estimate the effects of oral administration of BPA on rat liver and assess the possibility of recovery after cessation. Adult male albino rats were orally administered with BPA (50 mg/kg body weight) for 8 weeks, and then one group was left to recover for 4 weeks. Histological, immunohistochemical, biochemical, and quantitative real-time polymerase chain reaction assessments were performed. Loss of hepatic architecture, vascular dilatation congestion, and exudation, as well as cellular vacuolation, fat accumulation, and pyknotic nuclei were detected. Furthermore, inflammatory infiltration, localized metaplasia, and excessive collagen deposition in the portal triad were observed. Expression of Bcl-2-associated X protein and transforming growth factor beta 1 was prominent, denoting apoptosis and fibrosis. After the administration of BPA, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, and low-density lipoproteins were enhanced. Additionally, total protein, albumin, and high-density lipoproteins decreased. After a recovery for 4 weeks, hepatic cellular and vascular pathologies returned to normal, except for some inflammatory infiltration. Regarding biochemical affection, most of the parameters were directed toward normal during recovery. However, most of them were still significantly different from controls. This explored BPA hepatotoxicity from structural and functional aspects, and the possible spontaneous reversibility was confirmed. However, the precise mechanisms underlying hepatotoxicity or recovery need more in-depth investigations.

Chronic valproate treatment influences folliculogenesis and reproductive hormones with possible ameliorating role for folic acid in adult albino rats.

Sodium Valproate (VPA) is known to have deleterious consequences on ovarian function and folliculogenesis. Folic acid (FA) is associated with the quality of many parameters in folliculogenesis. Therefore, we aimed to investigate the effects of chronic Valproate administration on ovarian morphology, folliculogenesis, reproductive hormones, and the possible protective effect of Folic acid supplementation. Forty adult female albino rats were divided into four groups and treated orally for 90 days as follows: Control group received distilled water; FA group received (folic acid 400 µg/day); VPA group received (Na Valproate 200 mg/kg/day) and VPA + FA group received (Na Valproate 200 mg/kg/day + folic acid 400 µg/day). In addition, ovaries were processed for routine histology and immunohistochemistry (TGFß1 and PCNA) and reproductive hormones levels were measured. Results showed a significant decrease in number of follicles in VPA group, while atretic follicles increased compared with control group (P < 0.001). Interestingly, the number of follicles significantly increased in VPA + FA group compared with VPA group (P < 0.001). Also, number of atretic follicles significantly decreased in the VPA + FA group compared to the VPA group. Histochemistry score decreased for TGFß1 and PCNA staining in VPA group compared with control group (P < 0.01). Moreover, Valproate demonstrated a significant increase in testosterone levels in VPA group than control group (P < 0.001). However, VPA group demonstrated a significant decrease in levels of estradiol, progesterone, FSH and LH levels compared with control group. These changes were partially improved in VPA + FA group. In conclusion, FA co-treatment can modulate ovarian follicular and hormonal disturbances induced by valproate, which needs further investigations to identify the precise mechanisms.