In vitro assays for induction of drug metabolism.

Hepatic microsomal cytochrome P450 (CYP) forms have a major role in the metabolism of drugs and other chemicals. Primary hepatocyte cultures from humans and experimental animals are a valuable in vitro system for studying the effects of chemicals on CYP forms. This chapter describes methods to evaluate CYP form induction in human and rat hepatocytes cultured in a 96-well plate format.

Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes.

High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague-Dawley rat and human (both male and female) hepatocytes for 72 h with 0-1000 microM Pyrethrins and 0-1000 microM Phenobarbital did not result in any marked cytotoxicity.

A mode of action for induction of liver tumors by Pyrethrins in the rat.

High doses of Pyrethrins produce liver tumors in female rats. To elucidate the mode of action for tumor formation, the hepatic effects of Pyrethrins have been investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats' diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and 42 days followed by 42 days of reversal.

Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes.

The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets containing 1457 and 10,155 ppm butylated hydroxytoluene (BHT).

Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans.

Consumption of red meat is associated with an increased risk of colorectal cancer, whereas cruciferous vegetable consumption reduces cancer risk. While the mechanisms remain to be determined, cruciferous vegetables may act by altering the metabolism of carcinogens present in cooked food, such as the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The aim of this study was to evaluate the effect of cruciferous vegetable consumption on the metabolism of PhIP in 20 non-smoking Caucasian male subjects.

Metabolism of nicotine and induction of CYP1A forms in precision-cut rat liver and lung slices.

The aim of this study was to investigate xenobiotic metabolism and induction of cytochrome P450 (CYP) forms in precision-cut rat liver and lung slices, employing nicotine as a model compound. Freshly cut rat liver and lung slices metabolised nicotine to the major metabolite cotinine. Observed Km values for cotinine formation in liver and lung slices were 323 and 41.

Studies on the metabolism of the thiofurans furfuryl mercaptan and 2-methyl-3-furanthiol in rat liver.

The metabolism of two thiofurans, namely furfuryl mercaptan (FM) and 2-methyl-3-furanthiol (MTF), to their corresponding methyl sulphide and methyl sulphoxide derivatives has been studied in male Sprague-Dawley rat hepatocytes and liver microsomes. Rat hepatocytes converted FM to furfuryl methyl sulphoxide (FMSO) and MTF to 2-methyl-3-(methylthio)furan sulphoxide (MMFSO). Liver microsomes catalysed the NADPH-dependent metabolism of furfuryl methyl sulphide (FMS) to FMSO and 2-methyl-3-(methylthio)furan sulphide (MMFS) to MMFSO.