Cisplatin-Induced Oxidative Stress and Hepatorenal Damage: Implications From Preclinical Rat Models For Toxicological Pathology. | ||||
| Egyptian Journal of Veterinary Sciences | ||||
| Articles in Press, Corrected Proof, Available Online from 12 May 2025 PDF (2.59 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ejvs.2025.370322.2725 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Mohamed M. S. Gaballa1; Sally Elsharkawey2; Nehal ABD El-Mageed3; Ghada Gab Allah4; Ahmed El-Nemr5; Abdallah Elsaber6; Osama Ahmed7; Mohammed Marzouk8; Ibrahim Elmaghraby  9
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| 1Department of Pathology, Faculty of Veterinary Medicine, Benha University, Toukh, Qalyobiya, EgypT | ||||
| 2Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Egypt | ||||
| 3Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, 13736 Qaliobia, Egypt | ||||
| 4Department of Clinical Oncology &Nuclear medicine, Faculty of Medicine, Tanta University, Tanta, Egypt | ||||
| 5Medical Laboratory Technology Department, College of Health and Medical Techniques, Almaaqal University, Basra 61003, Iraq | ||||
| 6Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, 13736, QG, Egypt | ||||
| 7Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt; Department of Anatomy and Embryology, Veterinary Medicine Program, Benha National University, Egypt | ||||
| 8Biochemistry and molecular biology department, faculty of veterinary medicine, Benha university, benha, Egypt | ||||
| 9Department of Pathology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt | ||||
| Abstract | ||||
| Cisplatin, a cornerstone chemotherapeutic agent, is significantly limited by dose-dependent hepatorenal toxicity. This study comprehensively evaluated cisplatin-induced hepatorenal injury in a rat model using 5, 7, and 10 mg/kg doses, with biochemical, oxidative stress, and histopathological analyses at 3 and 5 days post-treatment. Liver toxicity manifested as dose- and time-dependent elevations in serum ALT and AST at 10 mg/kg by Day 5, correlating with histopathological evidence of hepatocellular necrosis, inflammatory infiltrates, and portal fibrosis. Oxidative stress in the liver was marked by increased lipid peroxidation and a compensatory but insufficient antioxidant response. Conversely, renal toxicity exhibited distinct oxidative dynamics, with elevated MDA and significant SOD depletion, indicating compromised antioxidant defenses. Renal dysfunction was evidenced by dose-dependent increases in serum creatinine and urea alongside histopathological findings of tubular necrosis, interstitial inflammation, and fibrosis. Histopathological scoring confirmed progressive injury, with hepatocellular damage and tubular necrosis peaking at 10 mg/kg by Day 5. Immunohistochemical analysis revealed heightened caspase-3 and TNF-α expression, implicating oxidative stress-mediated apoptosis and inflammation as central mechanisms. These findings highlight organ-specific antioxidant responses, with hepatic SOD activity transiently countering oxidative stress, while renal SOD depletion exacerbated damage. The temporal and dose-dependent progression of injury underscores the need for rigorous clinical monitoring and adjunct therapies, such as antioxidants or targeted drug delivery, to mitigate cisplatin’s toxicity without compromising its antitumor efficacy. This study provides critical insights into the mechanistic interplay of oxidative stress and organ damage, informing strategies to enhance therapeutic safety in oncology. | ||||
| Keywords | ||||
| Cisplatin; Biochemical changes; Oxidative stress; Hepatorenal damage; Rat | ||||
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