Comparative Nephroprotective Effects of Silymarin, N-Acetylcysteine, and Thymoquinone Against Carbon Tetrachloride-Induced Nephrotoxicity in Rats

Abstract

Background: Many pharmacological agents may lead to kidney damage. Preventing nephrotoxicity reduces the risk of morbidity and mortality, as well as decreasing hospitalization costs. Objectives: In this study, we investigated the comparative nephroprotective effects of silymarin, N-acetylcysteine (NAC), and thymoquinone (TQ) in animal models (rats) in which we induced nephrotoxicity using carbon tetrachloride (CCl4). Methods: This animal experimental study was conducted at the experimental animals center of Yuzuncu Yil University, Turkey, in 2015. Thirty-eight adult male Wistar rats were used in this study. We defined five experimental groups and treated them for four weeks. The first group (n = 8) was given no medicine. The second group (n = 8) was given only CCl4 (1.5 ml/kg, intraperitoneally (IP), in olive oil, twice a week). The third group (n = 6) was given TQ (10 mg/kg, IP, in dimethyl sulfoxide (DMSO), daily) and CCl4 (1.5 mL/kg). The fourth group (n = 8) was given silymarin (100 mg/kg, IP, in DMSO, daily) and CCl4 (1.5 mL/kg), while the fifth group (n = 8) was given NAC (10 mg/kg, IP, daily) and CCl4 (1.5 mL/kg). The kidneys of all the rats in every group were evaluated histologically using light microscopic methods at the end of the fourth week. A grading scheme was used to score the histological alterations related to tubular injury: absent (-), mild (+), moderate (++), severe (+++), and quite severe (++++). Results: In terms of the mean values of tubular damage, the first group had a mean of 0.0, the second group had 3.88 +/- 0.35, the third group had 1.00 +/- 0.89, the fourth group had 2.13 +/- 1.13, and the fifth group had 2.75 +/- 1.04. The results showed that, histopathologically, CCl4 had quite a severe toxic effect on the tubules when compared to the control group, although the glomeruli were intact. Silymarin, TQ, and NAC all showed statistically significant nephroprotective effects (P < 0.01). However, of the three, TQ was the most powerful nephroprotective agent (P < 0.01). Conclusions: In conclusion, we suggest that TQ may be used as a prophylactic agent against nephrotoxicity, especially in instances of tubular injury. However, human-based studies are still needed.