Possible mechanisms for N-acetyl cysteine and taurine in ameliorating acute renal failure induced by cisplatin in rats

• Published in: Toxicology mechanisms and methods 2011-09, Vol.21 (7), p.538-546
• Main Authors: Shalby, Aziza B., Assaf, Naglaa, Ahmed, Hanaa H.
• Format: Article
• Language: English
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - therapeutic use; Acute Kidney Injury - chemically induced; Acute Kidney Injury - prevention & control; Animals; Antineoplastic Agents - adverse effects; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biomarkers - blood; Biomarkers - urine; Cisplatin - adverse effects; Drug Administration Schedule; Female; inflammation; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Function Tests; Lipid Peroxidation - drug effects; NAC; Nephrotoxicity; oxidative stress; Rats; Rats, Sprague-Dawley; TAU; Taurine - administration & dosage; Taurine - therapeutic use
• ISSN: 1537-6516; 1537-6524
• DOI: 10.3109/15376516.2011.568985

Context: Cisplatin (CP), a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. Objective: In this study, the effect of N-acetyl cysteine (NAC) or taurine (TAU) for protection against CP-induced nephrotoxicity was investigated. Materials and methods: A single dose of CP 1 mg/kg b.wt. for 4 days was given IP to the rats, 10 days rest, and then the dose was repeated for other 4 days. After CP administration, NAC or TAU was given IP in a dose of 50 mg/kg b.wt. 3 times weekly for 8 weeks. Results: CP-induced nephrotoxicity is reflected in high values of blood urea and creatinine levels. In addition, the significant increase in the β2-MG and N-acetyl-β-glucosaminidase enzymes exhibited a strong correlation with histology scores of overall proximal tubule damage as compared with the normal control values. Treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic oxidation stress markers as compared with CP-treated group. On the other hand, treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic inflammation with possible attenuation of renal injury. Discussion: These data suggest that oxidative stress and inflammation are involved in the pathogenesis of CP-induced acute renal failure. The inhibition in oxidative stress and the elevation of the total antioxidant capacity as well as the inhibition of the inflammatory biomarkers by NAC or TAU after CP administration may play a central role in modulation of nephrotoxicity induced by CP. Conclusion: NAC and TAU have antioxidant and anti-inflammatory against CP-induced nephrotoxicity.