Effect of rutin on cisplatin-induced damage in human mesangial cells via apoptotic pathway.

Abstract

Cisplatin (CP) is one of the most effective and widely used compounds in the treatment of disease, including cancer, but is known to induce toxicity in patients. Rutin (RUT) is a flavonoid glycoside from Sophora japonica L. that has been shown to possess antioxidative, anti-inflammatory, and antiviral properties. RUT is also known to attenuate cardiotoxicity, isoproterenol-induced cardiac fibrosis, and ischemia/reperfusion-associated hemodynamic alteration, and prevents high glucose-induced renal glomerular endothelial hyperpermeability. In this study, we investigated the effect of RUT on CP-induced nephrotoxicity. CP was used to induce toxicity in human mesangial cells (HMCs), HMCs were pretreated with different concentrations of RUT before being exposed to 10 μg/mL of CP. A positive group was pretreated with antioxidant agent N-acetylcysteine prior to CP administration. At doses between 12.5 and 25 μM, RUT prevented CP-induced reduction in cell viability. Treatment with RUT suppressed intracellular reactive oxygen species and malonic dialdehyde levels and inhibited cell apoptosis. RUT reversed the CP-induced upregulation of p53, cleaved-caspase-3, and increased pro-caspase-3 and pro-caspase-9 levels. In conclusion, the RUT can relieve CP-induced nephrotoxicity by inhibiting the p53/caspase signaling pathway.

• Authors: Y Zhang, Q Wang, Y-D Wang, B Sun, X-W Leng, Q Li, L-Q Ren
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 38 Issue 1 Pg. 118-128 (Jan 2019) ISSN: 1477-0903 [Electronic] England
• PMID: 29962303 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Protective Agents
• Reactive Oxygen Species
• Tumor Suppressor Protein p53
• Rutin
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9
• Cisplatin

Topics

• Antineoplastic Agents (toxicity)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cells, Cultured
• Cisplatin (toxicity)
• Humans
• Mesangial Cells (drug effects, metabolism)
• Protective Agents (pharmacology)
• Reactive Oxygen Species (metabolism)
• Rutin (pharmacology)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (metabolism)