Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Food Chem Toxicol. 2010 Apr;48(4):1005-12. doi: 10.1016/j.fct.2009.12.027. Epub 2010 Jan 28.
The present study investigated the modulatory role of phenolic extract of soybean (PESB) in a rat model of nephrotoxic acute renal failure induced by cisplatin. Cisplatin (2 mg/kg/day) was administered to the rats for 5 days and the animals were pretreated with PESB (250-1000 mg/kg). Blood urea nitrogen reduced by 49.8% and 59.0%, serum creatinine by 34.7% and 62.1% and urinary N-acetyl-beta-D-glucosaminidase also decreased by 37.7% and 49.2% following treatment with 250- and 500-mg/kg doses of the extract respectively in the cisplatin-treated rats. The extract also significantly increased renal myeloperoxidase activity by 26.8% and 40.6% at these doses. PESB also decreased renal xanthine oxidase activity and serum nitrate/nitrite in the cisplatin-treated rats. In addition, PESB significantly attenuated the marked renal oxidative damage that accompanied cisplatin treatment. The extract improved liver histology and significantly increased the activities of the antioxidant enzymes measured [superoxide dismutase, catalase, glutathione-S-transferase], prevented glutathione depletion and decreased malondialdehyde level following cisplatin treatment. Furthermore, cisplatin-induced decrease in the activities of glucose-6-phosphatase and 5'-nucleotidase in these rats was attenuated only at 250 mg/kg dose of the extract. We concluded therefore that PESB via antioxidant and possibly anti-inflammatory actions offered protective benefit against cisplatin-mediated acute toxic injury to the kidney.
本研究探讨了大豆酚提取物(PESB)在顺铂诱导的大鼠肾毒性急性肾衰竭模型中的调节作用。顺铂(2mg/kg/天)连续给药 5 天,并用 PESB(250-1000mg/kg)预处理动物。PESB 250-和 500mg/kg 剂量组可使顺铂处理大鼠的血尿素氮分别降低 49.8%和 59.0%,血清肌酐降低 34.7%和 62.1%,尿 N-乙酰-β-D-氨基葡萄糖苷酶降低 37.7%和 49.2%。该提取物还分别使顺铂处理大鼠的肾髓过氧化物酶活性增加 26.8%和 40.6%。PESB 还降低了顺铂处理大鼠的肾黄嘌呤氧化酶活性和血清硝酸盐/亚硝酸盐。此外,PESB 显著减轻了顺铂处理伴随的明显肾氧化损伤。该提取物改善了肝组织学,并显著增加了抗氧化酶活性的测定[超氧化物歧化酶、过氧化氢酶、谷胱甘肽-S-转移酶],防止了顺铂处理后的谷胱甘肽耗竭和丙二醛水平的降低。此外,顺铂诱导的这些大鼠的葡萄糖-6-磷酸酶和 5'-核苷酸酶活性下降仅在 PESB 的 250mg/kg 剂量下得到缓解。因此,我们得出结论,PESB 通过抗氧化和可能的抗炎作用,为顺铂介导的急性肾毒性损伤提供了保护作用。