Augmentation of hepatic uridine-diphosphate glucuronyl transferase activity by antituberculous drugs in hamsters in vivo.
Changes in uridine-diphosphate glucuronyl transferase activity (UDP-GT) in liver homogenates of hamsters treated with different doses of isoniazid (INH), rifampicin (RMP), para-aminosalicylic acid (PAS) and hydrocortisone for several periods of time were studied and expressed as mg of bilirubin conjugated per g of protein per h. INH, RMP, PAS and hydrocortisone induced UDP-GT activity to a statistically significant degree. The optimum dose for high induction was 20 mg for INH, RMP and hydrocortisone, and 200 mg for PAS per kg of body weight. The optimum time of treatment for high induction was 10 consecutive days of intraperitoneal administration for all drugs examined. Such data, particularly for INH and RMP, indicate why patients who receive these drugs show no clinical jaundice, although they develop an hepatitis-like disease with elevation of serum transaminase of hepatic origin. This could be the result of stimulation of the hepatic smooth endoplasmic reticulum which produces rapid conjugation and therefore excretion of bilirubin. Similarly, the antituberculous drugs may cause liver dysfunction by inducing other liver enzymes.
D010131:Aminosalicylic Acid / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001663:Bilirubin / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D012293:Rifampin / Q000494:pharmacology; D013997:Time Factors
D000995:Antitubercular Agents; D010131:Aminosalicylic Acid; D014453:Glucuronosyltransferase; D001663:Bilirubin; D007538:Isoniazid; D012293:Rifampin; D006854:Hydrocortisone