INHIBITION OF CLASTOGENIC EFFECT OF CYCLOPHOSPHAMIDE AND MITOMYCIN-C BY NEEM LEAF-EXTRACT IN MICE

Azadirachta indica commonly known as 'Neem' is well known for its medi cinal properties in the indigenous Indian system of medicine. Almost e very part of the tree has some beneficial use. The anticlastogenic act ivity of 'Neem' against cyclophosphamide (CP) and mitomycin C (MMC) wa s studied in vivo in bone marrow cells of mice. Aqueous leaf-extracts of A. indica were injected intraperitoneally at doses 3, 6, 12 and 24 mg/kg body weight. Simultaneously, two known clastogens CP (10 mg/kg) and MMC (1.5 mg/kg) were administered individually to animals treated with 6 and 12 mg/kg of the leaf-extract. The end-points screened were chromosomal aberrations and damaged (aberrant) cells. Neem leaf-extrac t per se was found to be a weak clastogen; 6 and 12 mg/kg of the leaf- extract inhibited the clastogenicity of CP and MMC. The extent of inhi bition was different for the two clastogens. An ANOVA test showed that the reduction in the frequency of chromosomal aberrations was signifi cantly less when the leaf-extract was given in combination with CP. MM C co-administered with the leaf-extract showed a trend that was not st atistically significant. The difference may be attributed to the degre e of modulation of bioactivation of cytochrome P-450 enzymes, or the r epair of damaged DNA or a difference in detoxification of the reactive species of the two genotoxicants. (C) 1998 John Wiley & Sons: Ltd.