griseofulvin and Body-Weight

The relationship between haem biosynthesis and intestinal iron absorption in mice was investigated by ascertaining the effect of the haem synthesis inhibitor, griseofulvin, on duodenal iron absorption using both in vivo and in vitro measurements. Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3-7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT-1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem-arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5-aminolaevulinic acid, regulate intestinal iron absorption.

Topics: Administration, Oral; Aminolevulinic Acid; Animals; Biological Transport; Body Weight; Cation Transport Proteins; Drug Interactions; Duodenum; Gene Expression; Griseofulvin; Heme; In Vitro Techniques; Intestinal Absorption; Iron-Binding Proteins; Iron, Dietary; Liver; Male; Mice; Organ Size; Porphobilinogen

Five days intraperitoneal administration of rats with chlordiazepoxide (0.4 mg/kg), griseofulvin (7 mg/kg), rifampicin (8. 6 mg/kg), phenytoin (4.3 mg/kg) and phenobarbitone (1.4 mg/kg; an established inducer of microsomal enzymes) caused a significant increase in serum triacylglycerol (P<0.001) and the activities of aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase (P<0.001). Aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase activities were increased 1.48-, 1.15- and 1.47-fold, respectively, in chlordiazepoxide-treated rats, 1.65-, 1.20- and 1.38-fold in griseofulvin-treated rats, 1.74-, 1.36- and 1.44-fold in rifampicin-treated rats, 1.56-, 1.29- and 1.62-fold in phenytoin-treated rats and 2.26-, 1.72- and 1.93-fold in phenobarbitone-treated rats. Chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone increased the activity of cytosolic phosphatidate phosphohydrolase by 52, 58, 67, 73 and 82%, respectively, while the drugs elicited 50, 60, 60, 73 and 87% increases in the activity of the microsomal phosphatidate phosphohydrolase. Similarly, chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone elicited 2.4-, 2.39-, 2.34-, 1.69- and 3.75-fold increases in serum triacylglycerol concentrations. The correlations between serum triacylglycerol concentrations and the activities of aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase were significant in all treatment groups (r=0.83, r=0.92 and r=0.87, respectively, n=30, P<0.001). Our results suggest that induction of hepatic enzymes by the administered drugs may lead to hypertriglyceridaemia as an adverse effect, possibly by inducing the activity of regulatory enzymes in the biosynthesis of triglyceride.

Topics: Aminopyrine N-Demethylase; Aniline Hydroxylase; Animals; Body Weight; Chlordiazepoxide; Cytosol; Enzyme Activation; Enzyme Induction; Enzyme Inhibitors; Griseofulvin; Inactivation, Metabolic; Liver; Male; Microsomes, Liver; Organ Size; Oxidoreductases, O-Demethylating; Phenytoin; Phosphatidate Phosphatase; Rats; Rats, Wistar; Rifampin; Triglycerides

This study was designed to investigate the effects of griseofulvin, 5-fluorocytosine (5-FC), and amphotericin B on pancreatic and gastric secretion after the administration of a single large dose, or repeated small doses for 3 weeks, in male albino rats. The exocrine functions of the main digestive glands were only slightly affected by griseofulvin and were not affected by 5-FC. In contrast, a single large dose of amphotericin B caused a marked inhibition of exocrine functions of the main digestive glands. The rats treated with 5-FC lost body weight markedly during 2 weeks of administration.

Topics: Amphotericin B; Animals; Antifungal Agents; Bile; Body Weight; Female; Flucytosine; Gastric Juice; Griseofulvin; Pancreatic Juice; Rats

Topics: Animals; Body Weight; Cytochrome P-450 Enzyme System; Cytochromes; Fatty Acid Desaturases; Griseofulvin; Heme; In Vitro Techniques; Lipid Metabolism; Liver; Male; Mice; Microsomes, Liver; Mixed Function Oxygenases; NAD; NADP; Organ Size; Proteins; Time Factors

Topics: Adenoma; Animals; Benzopyrenes; Body Weight; Croton Oil; Depression, Chemical; Drug Synergism; Female; Griseofulvin; Lung Neoplasms; Lymphoma; Mammary Neoplasms, Experimental; Mice; Papilloma; Skin Neoplasms

Topics: Animals; Animals, Newborn; Benzopyrenes; Body Weight; Drug Synergism; Glycols; Griseofulvin; Mice; Oxides; Pesticides

Topics: Animals; Body Weight; Ectromelia; Griseofulvin; Liver; Male; Mice; Organ Size