Changes in the Expression of Hepatic Cytochrome P450 Isoenzymes 2El, 2B 1/2, 4A, and 2C6 in Mice Infected with Different Levels of Schistosoma Mansoni Cercariae

Most xenobiotic agents are metabolized by cytochrome P450 system. In the present study, Western blotting was used to investigate the effect of different levels of Schistosoma mansoni infection on the expression of somr cytochrome P450 isozymes (CYP 2E1, 2B1/2, 2C6, 4A), and to enzyme assay their related metabolic functions in mouse liver microsomes. Male mice were infected with 60, 120, 180, 300, and 600 S. mansoni cercariae per mouse for 33 days and compared with control. The signal intensity for CYP 2E1 was greatly increased over the control at 60,120, 180, and 300 cercariae/mouse with no change at the last level of S. mansoni infection. Also, the expression of CYP 4A was potentially induced at all levels of S. mansoni infection. A significant induction of CYP 2B1/2 expression was observed at all levels of S. mansoni infection with loss of signal at 180 cercariae/mouse. In contrast, CYP 2C6 expression was induced at the first two levels and such expression was decreased at the last three levels. In addition, Infection of mouse with 60, 120, and 180 cercariae/mouse decreased; [1] 7-methoxycoumarin O-demethylase activity by 36, 54, and 58% respectively; [2] 7-ethoxycoumarin O-deethylase activity by 33, 40, and 57% respectively; [3] coumarin hydroxylase activity by 35, 45, and 55% respectively. However, 300 and 600 cercariae/mouse induced: [1] 7-methoxycoumarin O-demethylase activity by 45 and 97% respectively; [2]; 7-ethoxycoumarin O-deethylase activity by 26 and 90% respectively; [3] coumarin hydroxylase activity by 100 and 200% respectively. In addition, all levels of S. mansoni infection decreased the sleeping time caused by hexobarbital. It is concluded that different levels of S. mansoni infection change the expression of different CYP isozymes andthat these alterations could enhance the carcinogenicity of jY-nitrosamines which is mainly dependent on CYP 2E1. The alterations in the expression of CYP 2E1, 4A and 2B1/2 isozymes as a result of S. mansoni infection may change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis