Badary O A
Department of Pharmacology, College of Pharmacy, Al Azhar University, Cairo, Egypt.
J Ethnopharmacol. 1999 Nov 1;67(2):135-42. doi: 10.1016/s0378-8741(98)00242-6.
The effect of thymoquinone (TQ), the main constituent of the Nigella sativa L. oil, on ifosfamide (IFO)-induced Fanconi syndrome (FS) and its antitumor activity were investigated in rats and mice, respectively. In rats, a daily injection of IFO (50 mg/kg per day, i.p.) for 5 days induced a FS characterized by wasting off glucose, electrolytes and organic acids, along with elevated serum creatinine and urea, as well as decreased creatinine clearance rate. Administration of TQ with the drinking water of rats, (5 mg/kg per day) for 5 days before and during IFO treatment, ameliorated the severity of IFO-induced renal damage. TQ significantly improved IFO-induced phosphaturia, glucosuria, elevated serum creatinine and urea, and significantly normalized creatinine clearance rate. Moreover, TQ significantly prevented IFO-induced renal glutathione (GSH) depletion and lipid peroxide accumulation. In mice bearing Ehrlich ascites carcinoma (EAC) xenograft, TQ (10 mg/kg per day) administered in drinking water significantly enhanced the antitumor effect of IFO (50 mg/kg per day, i.p. on days 1-4 and 15-18). Furthermore, mice treated with IFO in combination with TQ showed less body weight loss and mortality rate compared to IFO single therapy. These observations demonstrate that TQ may improve the therapeutic efficacy of IFO by decreasing IFO-induced nephrotoxicity and improving its antitumor activity.
分别在大鼠和小鼠中研究了黑种草子油的主要成分百里醌（TQ）对异环磷酰胺（IFO）诱导的范科尼综合征（FS）的影响及其抗肿瘤活性。在大鼠中，每天腹腔注射IFO（50mg/kg/天），连续5天，可诱导出一种FS，其特征为葡萄糖、电解质和有机酸流失，血清肌酐和尿素升高，肌酐清除率降低。在IFO治疗前及治疗期间，给大鼠饮用含TQ（5mg/kg/天）的水5天，可减轻IFO诱导的肾损伤严重程度。TQ显著改善了IFO诱导的磷酸盐尿、糖尿、血清肌酐和尿素升高，并显著使肌酐清除率恢复正常。此外，TQ显著预防了IFO诱导的肾谷胱甘肽（GSH）耗竭和脂质过氧化物积累。在携带艾氏腹水癌（EAC）异种移植瘤的小鼠中，饮用含TQ（10mg/kg/天）的水可显著增强IFO（50mg/kg/天，在第1 - 4天和第15 - 18天腹腔注射）的抗肿瘤作用。此外，与IFO单一疗法相比，接受IFO与TQ联合治疗的小鼠体重减轻和死亡率更低。这些观察结果表明，TQ可能通过降低IFO诱导的肾毒性并提高其抗肿瘤活性来改善IFO的治疗效果。
