Objective: To evaluate the protective effects of fulvic acid against amoxicillin-clavulanateinduced 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.

Purpose: Ischemia and reperfusion (I/R) can cause significant functional impairments in cells and tissues depending on the duration of ischemia. To date, many alternative treatments have been utilized to address this damage. We aimed to research the protective efficacy of taxifolin (Tax), a natural antioxidant, against liver I/R injury in terms of biochemical, histopathologic, and immunohistochemical parameters. Methods: The rats utilized in our study were randomly chosen and divided into four equal groups. Group 1 (n = 7), sham group received 1 mL saline orally; group 2 (n = 7), Tax group; Group 3 (n = 7), I/R group; group 4 (n = 7), Tax + I/R group as designated. The entire study was performed under general anesthesia with protection of animal welfare. Malondialdehyde (MDA) and interleukin-6 (IL-6) were analyzed from blood samples. Proapoptotic (B-cell lymphoma 2 [Bcl-2]-associated X protein [Bax]) and antiapoptotic (Bcl-2) amendments in cells were reviewed. Results: MDA grades were lower in the Tax+I/R group compared to the I/R group. Likewise, IL-6 grades were lower in the Tax + I/R group, histologic examinations showed that Bax proteins were less expressed in the Tax + IR group, and Bcl-2 proteins were intensely expressed in the Tax group. Conclusion Taxifolin applied before liver I/R demonstrated favorable effects on inflammation, oxidative stress, and proapoptotic changes.