Aly Fawzia A E, Donya Souria M
Department of Genetics and Cytology, National Research Centre, Dokki, Cairo, Egypt.
Mutat Res. 2002 Jun 27;518(1):1-7. doi: 10.1016/s1383-5718(02)00037-2.
-The genotoxic effect of rifampicin (RMP), one of the most active antituberculosis agents is studied. Also, the possible protection provided by the natural antioxidant vitamins C (VC) and E (VE) against the genotoxic effect of RMP is assessed. Mice were orally treated by gavage with 10, 50, 150 and 300 mg RMP kg(-1) body weight (bw). Also, oral treatment was conducted with RMP plus the vitamins. Mice received 300 mg RMP kg(-1) bw plus 100, 200 and 400mg VC or VE kg(-1) bw. Samples were taken 24h after the treatment. Repeated treatments with: (1) the therapeutic dose of RMP (10 mg kg(-1) bw); (2) RMP plus a dose of 25, 50 and 75 mg VC kg(-1); (3) RMP plus 10, 20 and 40 mg VE kg(-1) bw for 30 consecutive days were conducted. The tested doses of RMP induced a significant increase in the percentage of chromosome aberrations. However, a lower percentage of chromosome aberrations was observed when animals were treated with the therapeutic dose for 30 consecutive days. The obtained results revealed that chromosome aberrations induced by RMP decreased to a significant extent when mice were treated with RMP plus VC. The repeated doses of VC reduced the percentage of chromosome aberrations induced by RMP in a significant and dose-dependent manner. On the other hand, repeated doses of VE were not very effective in reducing the percentage of chromosome aberrations induced by RMP. Only the highest dose (3 x 40 mg kg(-1) bw) showed a significant effect (P<0.01). The results on the induction of chromosome damage clearly show that only VC appears able to efficiently protect the bone-marrow cells when given together with RMP, while no significant reduction in the yield of chromosome aberrations was observed for VE in combination with the antituberculosis drug.
研究了最有效的抗结核药物之一利福平（RMP）的遗传毒性作用。此外，还评估了天然抗氧化剂维生素C（VC）和维生素E（VE）对RMP遗传毒性作用的可能保护作用。通过灌胃对小鼠进行口服治疗，给予10、50、150和300mg RMP/kg体重（bw）。此外，还用RMP加维生素进行口服治疗。小鼠接受300mg RMP/kg bw加100、200和400mg VC或VE/kg bw。治疗后24小时采集样本。进行了以下重复治疗：（1）RMP治疗剂量（10mg/kg bw）；（2）RMP加25、50和75mg VC/kg；（3）RMP加10、20和40mg VE/kg bw，连续30天。测试剂量的RMP导致染色体畸变百分比显著增加。然而，当动物连续30天接受治疗剂量时，观察到的染色体畸变百分比较低。所得结果表明，当小鼠用RMP加VC治疗时，RMP诱导的染色体畸变显著减少。VC的重复剂量以显著且剂量依赖的方式降低了RMP诱导的染色体畸变百分比。另一方面，VE的重复剂量在降低RMP诱导的染色体畸变百分比方面效果不太显著。只有最高剂量（3×40mg/kg bw）显示出显著效果（P<0.01）。关于染色体损伤诱导的结果清楚地表明，只有VC与RMP一起给药时似乎能够有效保护骨髓细胞，而VE与抗结核药物联合使用时未观察到染色体畸变率有显著降低。
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