Nivolumab and bevacizumab attenuate cisplatin-induced hepatic inflammation and apoptosis in rats.

Background and Aim: Hepatotoxicity represents a significant adverse effect associated with cancer treatment. The present study was designed to evaluate the possible hepatoprotective effects of bevacizumab and nivolumab when administered concomitantly with cisplatin. Materials and Methods: A total of forty-two male Wistar Albino rats were randomly allocated into six groups: control, bevacizumab (10 mg/kg), nivolumab (3 mg/kg), cisplatin (12 mg/kg), cisplatin plus bevacizumab, and cisplatin plus nivolumab. Histological assessment of liver tissues was performed using hematoxylin and eosin (H&E) and Masson's trichrome staining. Immunohistochemical evaluation was conducted for inflammatory markers (TNF-α, IL-6), the angiogenic factor VEGF, and apoptotic markers (Bax, Bcl-2, Caspase-3). Results: Administration of cisplatin resulted in hepatotoxic changes, including disruption of normal hepatic cord architecture, cytoplasmic vacuolization, hemorrhage, mononuclear cell infiltration, and enhanced collagen accumulation. Co-treatment with bevacizumab or nivolumab significantly alleviated these histopathological changes (p<0.001). In addition, levels of inflammatory and pro-apoptotic markers (TNF-α, Bax, Caspase-3) were markedly reduced, whereas expression of the anti-apoptotic protein Bcl-2 was increased in the combination treatment groups compared with the cisplatin-only group. In the cisplatin + nivolumab group, the TNF-α level was 1.0 (0.8-1.2), whereas in the cisplatin-only group it was 2.0 (1.8-2.0) (p=0.03). The Bcl-2 level in the cisplatin + nivolumab group was 1.0 (0.8-1.2), while it was 0.2 (0-0.6) in the cisplatin group (p=0.04). Conclusion: Bevacizumab and nivolumab exhibited hepatoprotective properties when combined with cisplatin, as demonstrated by histological improvement and regulation of inflammatory and apoptotic signaling pathways.