Genotoxic and Cytotoxic Effects of Fumagillin in White Mice

Abstract

Fumagillin (dicyclohexylamine) which secreted by Aspergillus fumigates, is a natural antibiotic, used in veterinary medicine against microsporidiosis in bees and fish. in human medicine it used for the treatment of intestinal amebiasis, microsporidial keratoconjunctivitis and intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with AIDS and other types of immunodeficiency. In our current study, the genotoxicity of fumagillin was evaluated in mouse bone marrow cells using the micronucleus (mn) test, chromosome aberrations in bone-marrow cells and primary-spermatocytes. Mitotic index (MI) wase used to evaluate cytotoxic effects of Fumagillin. Fumagillin was administered to whit mice by gavage in doses of 10, 15, and 20 mg/kg.bwt prepared in 50% sugar solution, repeated for 7days at 24h intervals, with water-sugar syrup 50% as the negative control and Methotrexat as the positive control (20 mg/kg. bwt.) intrapretonial injection. The results of current study shows that Two of experimental doses of fumagillin 15 and 20 mg/kg. bwt. induced a significant increase p≤ 0.05 in the frequency of MN (24.60 ± 2.37 and 53.00 ± 4.59 respectively) compared with the negative control (8.20 ± 1.39). Significant increase p≤ 0.05 in means of total structural chromosome aberrations (9.00 ± 0.92 and 17.20 ± 1.24 compared with 6.00 ± 0.83 of negative control in bone marrow. In primary spermatocytes, the dose 20 mg/kg. bwt of fumagillin induced significant increase p≤ 0.05 in mean of aberration (14.00 ± 2.07 compared with 3.40 ± 0.50 of negative control. All experimental doses induced significant decrease p≤ 0.05 in MI (3.90 ± 0.29, 3.60 ± 1.80 and 2.90 ± 1.80 respectively) compared with (7.10 ± 0.29) in negative control. These results suggest that fumagillin (dicyclohexilamine) has an anti proliferative and genotoxic potential in mammal in vivo tests.