Chrysin attenuates pentadecafluorooctanoic acid-induced hepatotoxicity in male Wistar rats via modulation of oxidative stress, inflammation, and metabolic dysfunction

Abstract

Pentadecafluorooctanoic acid (PFOA), a persistent environmental pollutant, has been implicated in hepatotoxicity through mechanisms involving oxidative stress, inflammation, and metabolic dysfunction. This study investigated the hepatoprotective effects of chrysin against PFOA-induced liver injury in male Wistar rats. Twenty-five male Wistar rats were randomly divided into five groups (n = 5): control (20% dimethyl sulfoxide), PFOA (5 mg/kg), PFOA + chrysin (25 mg/kg), PFOA + chrysin (50 mg/kg), and chrysin only (50 mg/kg). Treatments were orally administered for 14 days. Serum and hepatic biomarkers of liver function, oxidative stress, inflammation, membrane integrity, and energy metabolism were evaluated using standard biochemical assays and enzyme-linked immunosorbent assay methods. PFOA exposure significantly (p < 0.05) increased serum liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase), lipid peroxidation marker (malondialdehyde), and pro-inflammatory cytokines (interleukin 1 beta and interferon gamma), while significantly reducing antioxidant parameters (glutathione, catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase, nitric oxide (NO), and membrane-bound enzyme activities, including adenosine triphosphatase (ATPase), Ca2+/Mg2+ ATPase, and 5’-nucleotidase. Chrysin treatment at both 25 and 50 mg/kg significantly (p < 0.05) ameliorated these alterations in a dose-dependent manner, with the 50 mg/kg dose showing greater protective efficacy. The findings indicate that PFOA-induced hepatotoxicity is associated with oxidative stress, inflammation, and metabolic dysfunction, whereas chrysin pre-treatment restores antioxidant defenses, attenuates inflammatory responses, and normalizes membrane-associated enzyme activities. Overall, chrysin demonstrates potent protective potential against PFOA-induced liver injury and may serve as a promising therapeutic candidate for environmental toxin-associated hepatotoxicity.