In vivo antimutagenic effect of vitamins C and E against rifampicin-induced chromosome aberrations in mouse bone-marrow cells.

摘要

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 300mg RMPkg(-1) body weight (bw). Also, oral treatment was conducted with RMP plus the vitamins. Mice received 300mg RMPkg(-1) bw plus 100, 200 and 400mg VC or VEkg(-1) bw. Samples were taken 24h after the treatment. Repeated treatments with: (1) the therapeutic dose of RMP (10mgkg(-1) bw); (2) RMP plus a dose of 25, 50 and 75mg VCkg(-1); (3) RMP plus 10, 20 and 40mg VEkg(-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 (3x40mgkg(-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.