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

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 400 mg VC or VE kg(-1) bw. Samples were taken 24 h 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. (C) 2002 Elsevier Science B.V. All rights reserved.