Investigation of lipid peroxidation as probable mechanism of rifampicin toxicity in vivo

BACKGROUND Xenobiotics may exert their toxic effects on tissues directly or after they have been metabolized. Increased reactivity of xenobiotics owing to their conversion to electrophiles, free radicals, nucleophiles and redox-active reactants may also contribute to toxicity. PURPOSE The present study attempts to investigate the possible "lipid peroxidation/free radical generation" mechanism behind rifampicin toxicity. METHODS Measurement of antioxidant enzymatic activity and MDA level was done according to standard procedures. RESULTS The results showed a low, non-significant (p > 0.05) increase in the malondialdehyde (MDA) levels of the testes, serum, brain and liver of Rif treated group compared with the control. The superoxide dismutase (SOD) results in Rif treated group also showed a low, non-significant (p > 0.05) decreased levels in the testes, serum, brain and liver when compared with the control. However, there was a significant (p ≤ 0.05) decrease in the level of catalase in the testes of Rif treated rats compared with the control. CONCLUSION The low, non-significant (p > 0.05) increase in the Malondialdehyde (MDA) levels of the testes, serum, brain and liver suggest that Rif toxicity may also be through other mechanisms such as direct toxic effects on cells, cellular dysfunction, conversion of Rif to electrophiles, nucleophiles and redox-active reactants; other than only via lipid peroxidation. It may be concluded that just as a lot of attention is directed towards targeting drug toxicity arising due to free radical generation by the use of antioxidants, similarly other mechanisms leading to drug toxicity should also be targeted.