Preventive effects of 5-hydroxy-1-methylhydantoin on paraquat-induced nephrotoxicity in rat

Abstract

To investigate the protective effects of 5-hydroxy-1-methylhyantoin (HM ) on paraquat (PQ)-induced nephrotoxicity in rat and its possible mechanism. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into four groups: namely control, PQ, vitamin C and HMH groups, with 6 rats in each group. The rats in control group were given an injection of 2 mg/kg of normal saline intraperitoneally. The rats in PQ group were given an injection of 50 mg/kg of PQ intraperitoneally. The rats in vitamin C and HMH groups were given 1 mmol/kg of vitamin C or HMH through gastric tube right after PQ injection. The hydroxyl free radical scavenging ability of HMH and vitamin C was determined by Fenton method. Blood sample was collected after 24 hours of PQ treatment, then the animals were sacrificed and renal tissues were harvested. Blood urea nitrogen (BUN), serum creatinine (SCr), protein content of renal cortex, blood malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) activity were determined. Both vitamin C and HMH showed a very good ability to scavenge hydroxyl radicals, and the 50% inhibiting concentration (IC₅₀) was both 4.02 mg/mL. Compared with control group, serum BUN, SCr and MDA in renal tissue were significantly increased in PQ group, and the protein, GSH contents and SOD activity were significantly decreased [BUN (mmol/L): 40.80 ± 2.49 vs. 13.67 ± 1.58, SCr (μmol/L): 163.46 ± 8.67 vs. 51.80 ± 4.37, MDA (nmol/g): 7.51 ± 0.23 vs. 4.52 ± 0.33, protein (μmol/L): 0.94 ± 0.14 vs. 1.35 ± 0.10, GSH (mg/g): 1.08 ± 0.48 vs. 3.30 ± 0.44, SOD (kU/L): 70.74 ± 6.42 vs. 112.89 ± 8.72, all P < 0.01 ]. Compared with PQ group, serum BUN and SCr and MDA in kidney tissue in vitamin C and HMH groups were significantly decreased, and GSH content and SOD activity in kidney tissue were significantly elevated [BUN mmol/L): 22.64 ± 2.36, 18.71 ± 5.23 vs. 40.80 ± 2.49, SCr (μmol/L): 97.28 ± 4.81, 89.20 ± 6.72 vs. 163.46 ± 8.67, MDA (nmol/g): 4.67 ± 0.31, 4.21 ± 0.42 vs. 7.51 ± 0.23, GSH (mg/g): 1.78 ± 0.10, 1.86 ± 0.39 vs. 1.08 ± 0.48, SOD (kU/L): 98.69 ± 5.43, 103.76 ± 4.45 vs. 70.74 ± 6.42, all P < 0.01]. Compared with vitamin C group, HMH could significantly reduce SCr contents P < 0.05). There were no differences in reduction PQ-induced BUN, MDA content, and effect on GSH content and SOD activity between vitamin C group and HMH group (all P > 0.05). HMH can protect the kidney against PQ-induced nephrotoxicity, and the mechanism of which maybe attributed to its anti-oxidation property and ability to scavenge hydroxyl radical.