Rifampicin: Cytotoxic and Genotoxic Action

Abstract

Rifampicin (Rif) is an effective liver enzyme inducer, promoting the up-regulation of hepatic cytochrome P450 enzymes such as CYP2D6 and CYP3A4. Although an earlier report by the International Agency for Research on Cancer (IARC) indicated that there was not enough data to suggest that Rif should be classified as a carcinogen, recent studies have documented this antibiotic to be mutagenic. Rif remains, however, a first line drug in the management of tuberculosis. The purpose of this study was to investigate the cytotoxic and genotoxic effects of Rif to better understand its mutagenicity. The study was carried out using three methods: Standard Allium cepa (Linn.) assay, modified Ames test (which is a modification of the standard Ames assay) and micronucleus test (an in vivo method devised primarily for screening chemicals for their chromosome-breaking effects). Our results indicate that Rif is mutagenic; mutagenicity depends on hepatic activation as indicated by the modified Ames assay. Rif also significantly (p<0.001) increase the distribution of polychromatophilic erythrocytes both in the blood and bone marrow of rats. There was also absolute inhibition of the root growth of A. cepa. These findings are simple but conclusive enough to say that Rif has a damaging effect on DNA.

KEY WORDS: Rifampicin, Micronucleus test, Ames assay, DNA, Mutagenicity