Comparison between the effect of pyrazole, cobalt and tin on hepatic and renal microsomal cytochrome P450 concentration and metabolism of coumarin and 7 ethoxycoumarin

ABSTRACT

Recently, the metabolism of coumarin and 7-ethoxycoumarin were reported to be enhanced several folds in the mouse liver after pretreatment with either N-containing heteroaromatic compounds [e.g. pyrazole, PL] or heavy metals [e.g. Cobalt, Co and Tin, Sn]. The effect of these compounds on the mouse renal microsomes is not thoroughly investigated. Accordingly the present study was designed to compare the effect of pyrazole. cobalt and tin on hepatic and renal microsomes. The study revealed that in both kidney and liver microsomes, the concentration of Cyt P450 was decreased to about the same extent after pretreatment of male mice [NMRI-type] with these compounds. In contrary the metabolism of 7-ethoxy-coumarin and of Coumarin were increased several folds. In the liver microsomes, the highest increase in the metabolism of the coumarin derivatives, were observed after pretreatment of mice with Sn [Sn > PL > Co]. On the other hand, in the kidney microsomes, the most potent inducer was found to be PL [PL> Co>Sn]. These results indicate that PL, Co or Sn enhance the hepatic and renal metabolism of coumarin derivatives by different rates. Accordingly, these data suggested the different regulation of the coumarin derivatives metabolizing enzymes in the -liver from that in the kidney