Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats

Abstract

Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N-acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC-TAU group, 5) CDDP group, 6) CDDP-NAC group, 7) CDDP-TAU group, and 8) CDDP-NAC-TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg) and/or TAU (50 mg/kg) were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect.

Keywords: N-acetylcysteine; cisplatin; nephrotoxicity; oxidative stress; taurine.

Figure 1

Effect of CDDP, NAC, and TAU both individually and in combination on (A) body weight change (%) and (B) kidney ratio (%) in male rats. Notes: Data are expressed as mean ± standard error (n=6). Bars not sharing common superscript letters (a–d) are significantly different (P≤0.05). Abbreviations: CDDP, cisplatin; NAC, N-acetylcysteine; TAU, taurine.

Figure 2

Effect of CDDP, NAC, and TAU both individually and in combination on (A) level of renal MDA (nmol/mg protein) and (B) serum TAC (mmol/L) in male rats. Notes: Data are expressed as mean ± standard error (n=6). Bars not sharing common superscript letters (a–d) are significantly different (P≤0.05). Abbreviations: CDDP, cisplatin; NAC, N-acetylcysteine; TAU, taurine; MDA, malondialdeyde; TAC, total antioxidant capacity.