Mechanistic pathways and in silico modeling of gallic acid–mediatedprotectionagainstdoxorubicin-inducednephrotoxicity in rats
Iranian Journal of Basic Medical Sciences, cilt.29, sa.4, ss.623-633, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 29 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.22038/ijbms.2026.90473.19500
- Dergi Adı: Iranian Journal of Basic Medical Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Index Islamicus, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Middle East & Africa Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.623-633
- Anahtar Kelimeler: Apoptosis, Doxorubicin, Gallic acid, Inflammation, Molecular docking, Nephrotoxicity Oxidative stress
- Atatürk Üniversitesi Adresli: Evet
Özet
A B S T R A C T Objective(s): This study aimed to evaluate the protective effects of Gallic acid (GA) against (Doxorubicin) DOX-induced renal injury and to explore potential molecular interactions underlying its effects. Materials and Methods: Fifty male rats were randomly assigned to five groups: Control, DOX, GA50+DOX, GA100+DOX, and GA100. DOX was administered as a single intraperitoneal dose on day 8 (40 mg/kg), while GA was given orally at 50 or 100 mg/kg for 10 consecutive days. Renal tissues were collected on day 11 and analyzed for oxidative stress markers, pro- and anti-inflammatory cytokines, and the apoptotic marker caspase-3 via ELISA. Immunohistochemistry assessed Nrf-2 and HO-1 expression, and histopathology evaluated structural alterations. Molecular docking simulations were performed for DOX/topoisomerase IIα (PDB ID: 4FM9) and GA/TNF-α (PDB ID: 2AZ5). Results: GA significantly ameliorated DOX-induced oxidative stress, inflammatory cytokine imbalance, caspase-3 activation, and histological damage in a dose-dependent manner, while enhancing Nrf-2 and HO-1 expression. Docking analysis confirmed DOX binding to topoisomerase IIα and revealed strong GA–TNF-α binding affinity. Conclusion: GA exerts substantial renoprotective effects against DOX-induced nephrotoxicity by modulating oxidative, inflammatory, and apoptotic pathways. The agreement between in vivo findings and in silico modeling supports GA as a potential complementary agent to reduce chemotherapy-related renal injury.