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

Mohamed, Mona Ali; Mehanna, Elsayed Eldeeb; Oda, Samah Shehata; Tohamy, Hossam Gaffar; Khafaga, Asmaa Fahmy

doi:10.21608/ejvs.2025.373295.2763

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

Document Type : Conference

Authors

¹ Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Egypt

² Department of Pathology, Faculty of Veterinary Medicine, Alexandria University

³ Department of pathology, faculty of veterinary medicine, Alexandria university

10.21608/ejvs.2025.373295.2763

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 1^st group was given corn oil as a vehicle (1ml/kg) and served as a control group; the 2^nd group received daily oral dose of BPA (250 mg/kg); the 3^rd group received daily oral dose of D-limonene (200 ml/kg); the 4^th 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.

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