Fulvic acid protects hepatic tissue from amoxicillin/clavulanate-induced hepatotoxicity.

IMPORTANCE

Fulvic acid can protect liver tissue against amoxicillin-clavulanate-induced hepatotoxicity through antioxidant and antiapoptotic effects.

OBJECTIVE

To evaluate the protective effects of fulvic acid against amoxicillin-clavulanate-induced hepatotoxicity using biochemical, histopathological, immunohistochemical, functional, and bioinformatic analyses.

METHODS

Twenty-eight male Wistar rats were randomly assigned to 4 groups (n = 7/group): sham (saline), amoxicillin-clavulanate (10 mg/kg/day), fulvic acid (100 mg/kg/day), and combined treatment. Treatments were administered orally for 21 days. Liver injury and oxidative stress were assessed by serum alanine aminotransferase, aspartate aminotransferase, malondialdehyde, total antioxidant status, and total oxidant status; tissue injury was assessed histologically. Apoptosis was evaluated by immunohistochemistry for BAX and BCL2. Hepatic detoxification capacity was assessed by a caffeine clearance test. In silico analyses predicted molecular targets of fulvic acid and enriched pathways.

RESULTS

Amoxicillin-clavulanate increased transaminases, oxidative stress markers, and proapoptotic signaling and induced vascular congestion and sinusoidal dilatation. Co-treatment with fulvic acid improved serum biomarkers, reduced histological injury, downregulated BAX, and restored BCL2 staining intensity. In silico analysis identified predicted fulvic-acid targets enriched in metabolic and proliferation-related pathways.

CONCLUSIONS AND RELEVANCE: Fulvic acid attenuated amoxicillin-clavulanate-induced hepatotoxicity, consistent with antioxidant and antiapoptotic mechanisms. Further studies are warranted to define dose-response relationships and translational potential.