Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver.
The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.
Ronsein
Graziella Eliza
GE
Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Guidi
Débora Bonelli
DB
Benassi
Jean Carlo
JC
Filho
Danilo Wilhelm
DW
Pedrosa
Roberto Coury
RC
Pedrosa
Rozangela Curi
RC
D000082:Acetaminophen / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D002227:Carbazoles; D005609:Free Radicals; D011412:Propanolamines; D000077261:Carvedilol; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010100:Oxygen