Mechanistic pathways and in silico modeling of gallic acid–mediated protection against doxorubicin-induced nephrotoxicity in rats

Document Type : Original Article

Authors

1 Atatürk University, Faculty of Veterinary Medicine, Department of Physiology, 25000 Erzurum, Turkey

2 Atatürk University, Faculty of Medicine, Department of Medical Pharmacology, 25000 Erzurum, Turkey

3 Atatürk University, Faculty of Veterinary Medicine, Department of Pathology, 25000 Erzurum, Turkey

4 Kyrgyzstan-Turkey Manas University, Faculty of Veterinary Medicine, Department of Pathology, 720007 Bishkek, Kyrgyzstan

5 Cairo University, Faculty of Veterinary Medicine, Department of Biochemistry, 3753450 Giza, Egypt

10.22038/ijbms.2026.90473.19500

Abstract

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.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 29, Issue 4
April 2026
Pages 623-633

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