Metoprolol and propranolol treatment in carbon tetrachloride-induced hepatic injury.
The effects of beta 1-selective metoprolol (CAS 37350-58-6) and the nonselective beta-adrenoceptor antagonist propranolol (CAS 525-66-6) were investigated in healthy and CCl4 damaged male rats. Treatments were performed for 16 days, orally with dosages reducing heart beat/min by 25% (metoprolol 10 mg/kg, propranolol 1 mg/kg). Liver glycogen content was not influenced by either beta-blocker in healthy animals. CCl4-induced loss of glycogen was equally moderated by metoprolol and propranolol. Blood glucose increased in metoprolol treated healthy and liver damaged rats after a single dosage likewise following prolonged treatment. Propranolol was without effect on blood glucose level. Cytochrome P-450 decline in microsomal fraction was greater in metoprolol, than in propranolol treated healthy animals. However, the severe fall elicited by liver injury was moderated by metoprolol and normalised by propranolol. Cytochrome b5 seems to be involved in metoprolol metabolism. Cytochrome P-450-dependent aminopyrine-N-demethylase was impeded by metoprolol in animals with healthy liver. The serious inhibition caused by CCl4 was moderated by metoprolol and with a better result by propranolol. The high serum bilirubin level in liver lesion was lowered by metoprolol and particularly by propranolol. Neither phase I metabolic process aminopyrine-N-demethylation nor phase II glucuronidation were normalised. A comparison of this data with the results of a previous 12-day treatment schedule indicates that no changes in efficacy occurred with longer treatment. The present results pertain to the importance of the selection of beta-adrenoceptor blocker in liver lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Kulcsár-Gergely
J
J
Department of Pharmacology, Medical University, Debrecen, Hungary.
Kulcsár
A
A
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D008112:Liver Glycogen; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D006899:Mixed Function Oxygenases; D000633:Aminopyrine N-Demethylase; D008790:Metoprolol; D001663:Bilirubin