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

Many pharmacological agents may lead to kidney damage. Preventing nephrotoxicity reduces the risk of morbidity and mortality, as well as decreasing hospitalization costs. 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). 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 (++++). 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). 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.