D-Limonene Alleviates Bisphenol-A Hepatotoxicity in Male Albino Rats via Suppression of Oxidative Stress and Inflammation

Abstract

Bisphenol-A (BPA) is a well-known synthetic endocrine disruptor that is used extensively in the production of thermal paper, epoxy resins, and polycarbonates. Bisphenol-A (BPA) exposure leads to oxidative damage and toxicity to hepatic cells. D-limonene possess anti-inflammatory, anticancer, antiapoptotic, and antioxidant effects. The current study was designed to evaluate the protective effect of D-limonene against BPA- induced hepatotoxicity in male albino rats. Forty male albino rats were divided into four equal groups (n=10). The 1st group was given corn oil as a vehicle (1ml/kg) and served as a control group; the 2nd group received daily oral dose of BPA (250 mg/kg); the 3rd group received daily oral dose of D-limonene (200 ml/kg); the 4th was received BPA (250 mg/kg b.wt) followed by D-limonene (200 ml/kg b.wt) orally daily. After 60 days, the results showed that BPA significantly elevated the serum levels of Aspartate transferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (ALP) and decreased serum iron level. Furthermore, BPA-intoxicated rats showed a marked rise in the activity of hepatic Malondialdehyde level (MDA) Reduced glutathione (GSH) and Glutathione peroxidase 4 (GPX4). Moreover, BPA-intoxicated rats revealed severe histopathological changes in liver tissue including degenerative changes in the hepatocytes, besides dilatation of hepatic sinusoids, portal-portal bridging necrosis (areas of confluent hepatocyte necrosis extend from one part tract to another, forming a bridge of necrosis) and fibrosis and infiltration of mononuclear cells in the portal area, along with a notable rise in immune-expression of P53 and cyclooxygenase-2 (COX-2) in hepatic tissues when compared to the control rats. Conversely, treatment with D-limonene alleviated the BPA-induced oxidative injury, histopathological alterations and immunohistochemical expression of P53 and COX-2. In conclusion, D-limonene is a promising natural medication that may be able to reduce BPA-induced hepatotoxicity by acting as an anti-inflammatory and antioxidant.