Gulec Mukaddes, Iraz Mustafa, Yilmaz H Ramazan, Ozyurt Huseyin, Temel Ismail
Division of Biochemistry, Akyurt Integrated Unit of Ankara Numune Education and Research Hospital, Ankara, Turkey.
Toxicol Ind Health. 2006 Apr;22(3):125-30. doi: 10.1191/0748233705th255oa.
This study was carried out to determine if Ginkgo Biloba Extract (GBE or Egb 761) exerts a beneficial effect against cisplatin-induced renal failure in rats. Sprague Dawley rats were divided into four groups. The first group (control) received orally 1 mL/kg/day of 0.9% saline by an oral carrier vehicle on days 1 to 10. The second group was injected with 7 mg/kg cisplatin intraperitoneally (i.p.) on the fourth day, once only. The third group (vit E+cisplatin) was administered 10 mg/kg/day i.p. vit E on 1 to 10 days with one dose of i.p. cisplatin (7 mg/kg) injection on the fourth day. The fourth group (GBE+cisplatin) was given GBE orally at 100 mg/mL/kg started on the first day up to the tenth day with one dose of cisplatin (7 mg/kg) injection on the fourth day. Cisplatin was found to lead a statistically significant increase in plasma BUN and creatinine levels, as well as urine micro total protein (MTP) levels, leading to acute renal failure (ARF) in rats. Renal xanthine oxidase (XO) activities increased in all groups (statistically significant in cisplatin + GBE-treated rats; P < 0.001). Adenosine deaminase (AD) activities were increased in cisplatin-treated rats, and decreased in cisplatin+GBE-treated (P < 0.041) and cisplatin+vit E-treated (P < 0.005) rats, compared to controls. Malondialdehyde (MDA), nitric oxide (NO) levels and myeloperoxidase (MPO) activities were increased in the kidney tissue of cisplatin-treated rats. Vit E improved plasma creatinine and urine MTP levels, together with tissue MDA, NO levels, and MPO activities. But GBE had no statistically significant effect on those parameters. These results indicate that increased XO, AD and MPO activities, as well as MDA and NO levels play a critical role in cisplatin nephrotoxicity. GBE has been shown to protect against cisplatin-induced nephrotoxicity.
本研究旨在确定银杏叶提取物（GBE或Egb 761）对顺铂诱导的大鼠肾衰竭是否具有有益作用。将Sprague Dawley大鼠分为四组。第一组（对照组）在第1至10天通过口服载体媒介物每日口服1 mL/kg的0.9%生理盐水。第二组在第四天腹腔注射一次7 mg/kg顺铂。第三组（维生素E+顺铂）在第1至10天腹腔注射10 mg/kg/天的维生素E，并在第四天注射一剂腹腔顺铂（7 mg/kg）。第四组（GBE+顺铂）从第一天开始至第十天口服100 mg/mL/kg的GBE，并在第四天注射一剂顺铂（7 mg/kg）。结果发现，顺铂导致大鼠血浆尿素氮和肌酐水平以及尿微量总蛋白（MTP）水平出现统计学显著升高，从而导致急性肾衰竭（ARF）。所有组的肾黄嘌呤氧化酶（XO）活性均升高（顺铂+GBE处理的大鼠具有统计学显著性；P<0.001）。与对照组相比，顺铂处理的大鼠腺苷脱氨酶（AD）活性升高，而顺铂+GBE处理（P<0.041）和顺铂+维生素E处理（P<0.005）的大鼠腺苷脱氨酶活性降低。顺铂处理的大鼠肾组织中丙二醛（MDA）、一氧化氮（NO）水平和髓过氧化物酶（MPO）活性升高。维生素E改善了血浆肌酐和尿MTP水平，以及组织MDA、NO水平和MPO活性。但GBE对这些参数没有统计学显著影响。这些结果表明，XO、AD和MPO活性增加以及MDA和NO水平在顺铂肾毒性中起关键作用。已证明GBE可预防顺铂诱导的肾毒性。
