Effects of 2-[1-(ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone on hepatic haem biosynthesis: species differences in hepatic porphyria.

2-[1-(Ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone (ETC) is a novel alkyl ketone herbicide. Continuous administration of ETC to mice for 28 days resulted in marked liver enlargement and severe intrahepatic cholestasis. These effects have been shown to result directly from a rapid and marked accumulation of porphyrin in the liver.

Comparison of the effects of griseofulvin and dihydropyridines on ferrochelatase activity and porphyrin accumulation in primary cultures of mouse and rat hepatocytes.

The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethyl pyridine (EDDC) and griseofulvin to induce porphyria in primary cultures of mouse and rat hepatocytes was determined. Exposure of mouse hepatocytes to DDC, EDDC or griseofulvin (5-100 mum) for 4 days resulted in a marked inhibition of ferrochelatase activity (up to 95%). However, whereas exposure of rat hepatocytes to DDC or EDDC (5-100 mum) for 4 days also resulted in marked inhibition of ferrochelatase activity (up to 96%), exposure to griseofulvin (5-100 mum) had no effect.

Reduced estradiol production by a substituted triazole results in delayed ovulation in rats.

Ovulation in the rat is delayed by a single administration of the substituted triazole R151885 (1,1-di(4-fluorophenyl)-2-(1,2,4-triazol-1-yl)-ethanol). This delay results from a 24-hr shift in the preovulatory luteinizing hormone (LH) surge since administration of chorionic gonadotrophin on proestrus restores ovulation. Plasma levels of estradiol are markedly reduced (42-45%) 6-12 hr after administration of R151885.

Ovulation in rats is delayed by a substituted triazole.

When a single oral dose of 5 or 25 mg/kg of the substituted triazole R151885 [1,1-di(4-fluorophenyl)-2-(1,2,4-triazol-1-yl)-ethanol] was administered at midday on diestrus-2 to rats with regular 4-day estrous cycles, the subsequent ovulation was delayed by 24 or 48 hr, respectively. There was no evidence of toxicity at the doses used. The only morphological changes detected in the reproductive tract were a delay in accumulation of uterine fluid and prolonged but normal follicular maturation prior to the delayed ovulation.