Department of Pharmacology and Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, 9177948564 Mashhad, I. R. Iran.
Ren Fail. 2010 Jun;32(5):612-7. doi: 10.3109/08860221003778056.
Hexachlorobutadiene (HCBD) is a potent nephrotoxin in rodents. Pharmacological studies have shown that pomegranate fruit preparations have antioxidant, anti-inflammatory chemopreventive effects. In this study, the effect of pomegranate seed oil (PSO) on HCBD-induced nephrotoxicity was investigated in adult male rats. Animals were divided into five groups. Group 1 was treated with corn oil (1 mL/kg, i.p.). Group 2 received a single dose of HCBD (50 mg/kg, i.p.). Groups 3-5 were treated with PSO (0.16, 0.32, and 0.64 mg/kg, i.p., respectively) 1 h before HCBD (50 mg/kg, i.p.) injection. A significant elevation of serum creatinine and urea (p < 0.001) levels as well as urine glucose and protein (p < 0.001) concentrations (as markers of acute renal failure) was observed 24 h after administration of HCBD as compared to control group. HCBD also caused a significant decrease in total thiol content (p < 0.001) and a significant increase in thiobarbituric acid reactive species (TBARS, as an index of lipid peroxidation) levels (p < 0.001) in kidney homogenate samples. PSO pretreatment resulted in a significant and dose-dependent decrease in serum creatinine (p < 0.001) and urea levels (p < 0.001) as well as urine glucose (p < 0.001) and protein concentrations (p < 0.001) when compared with HCBD treated alone. PSO also significantly reversed the HCBD-induced depletion in total thiol content (p < 0.001) and elevation in TBARS (p < 0.001) in kidney homogenate samples. The results of this study showed that PSO clearly attenuated HCBD-induced nephrotoxicity, but explanation and mechanism of this protection need further explorations.
六氯丁二烯 (HCBD) 是一种强烈的啮齿动物肾毒物。药理学研究表明,石榴果实制剂具有抗氧化、抗炎、化学预防作用。在这项研究中,研究了石榴籽油 (PSO) 对 HCBD 诱导的肾毒性的影响,该研究在成年雄性大鼠中进行。动物被分为五组。第 1 组用玉米油(1 mL/kg,ip)处理。第 2 组给予单次 HCBD(50 mg/kg,ip)。第 3-5 组分别在给予 HCBD(50 mg/kg,ip)前 1 小时用 PSO(0.16、0.32 和 0.64 mg/kg,ip)处理。与对照组相比,HCBD 给药 24 小时后,血清肌酐和尿素(p<0.001)水平以及尿葡萄糖和蛋白(p<0.001)浓度(作为急性肾衰竭标志物)显著升高。HCBD 还导致肾匀浆样本中总巯基含量(p<0.001)显著降低和丙二醛反应性物质(TBARS,作为脂质过氧化的指标)水平(p<0.001)显著升高。PSO 预处理可显著降低血清肌酐(p<0.001)和尿素水平(p<0.001)以及尿葡萄糖(p<0.001)和蛋白浓度(p<0.001),与单独给予 HCBD 相比,呈剂量依赖性降低。PSO 还显著逆转了 HCBD 诱导的肾匀浆样本中总巯基含量(p<0.001)的耗竭和 TBARS(p<0.001)的升高。本研究结果表明,PSO 明显减轻了 HCBD 诱导的肾毒性,但这种保护的解释和机制需要进一步探讨。