In vivo protective role of antioxidants against genotoxicity of metronidazole and azanidazole.

The mutagenicity of metronidazole and azanidazole has been extensively reported. Previous experiments demonstrated, by means of the intrasanguineous host-mediated assay, that they significantly induced mutagenicity in liver, kidney and lung of mice. The treatment of mice with butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) by two different routes of administration (i.p. injection and oral intubation) significantly reduced liver- and kidney-mediated mutagenicity of azanidazole and metronidazole. No significant differences were observed between the routes of treatment in terms of protective effect on genotoxicity of azanidazole in the considered organs, whereas i.p. administration was the most suppressive on the mutagenicity of metronidazole. Even if BHT was the most effective agent in preventing mutation induction in mice, a detectable toxicity, in terms of increased mutagenicity, was evaluated in the liver. Evidence of lung abnormalities was also seen. The results suggest that the possible adverse effects on biological systems limit the prophylactic use of BHA and BHT in preventing the action of chemical carcinogens in man.