Comparison of the therapeutic efficacy of 4-methylpyrazole and N-acetylcysteine on acetaminophen (paracetamol) hepatotoxicity in rats.
Obtaining effective analgesia with a minimal erosive effect on gastric mucosal tissue has increased the consumption of acetaminophen (paracetamol), especially among the elderly. However, the hepatotoxic effects of acetaminophen have also increased. We aimed to compare the effects of 4-methylpyrazole (4-MP), N-acetylcysteine (NAC) and their combined use on the hepatotoxicity of acetaminophen in a rat model. Male Wistar Albino rats were divided into six groups. Groups 1-5 received 2,000 mg/kg acetaminophen by gavage while the control group was group 6. Group 2 animals were given NAC (loading dose 140 mg/kg followed by seven doses at 4 h intervals); group 3 received 50 mg/kg 4-MP; group 4 received 200mg/kg 4-MP; and group 5 received NAC as in group 2 plus 200 mg/kg 4-MP. Blood samples were taken for measurements of serum AST and ALT levels. The livers of the rats were removed for microscopic examination and grading of hepatic necrosis. AST and ALT levels in groups 2-5 were lower than that of group 1 (p < 0.001), although no significant difference was noted between groups 2-5 (p > 0.05). Higher levels of ALT were found in group 5 than in group 2 (p < 0.05), and higher levels of AST were found in group 5 than in group 3 (p < 0.01). Median necrosis scores were 3.36 for rats receiving acetaminophen alone (p < 0.001, compared with groups 2-6), 1.45-1.81 for groups 2-5 (p > 0.05, compared with each other), and 0.18 for control rats (p < 0.001, compared with groups 1-5). In conclusion, the administration of 4-MP and/or NAC after 4 h of administering toxic dose of acetaminophen, inhibits hepatotoxicity in rats. There was no difference between the 4-MP and NAC-treated groups as reflected by comparable levels of serum transaminases and the degree of hepatic necrosis. Combining of 4-MP and NAC offers no benefit.
Küçükardali
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Y
Department of Internal Medicine, GATA Haydarpaşa Eğitim Hastanesi, Iç Hastaliklari Kliniği, Kadiköy-Istanbul, Turkey. ykuc@turk.net.tr
Cinan
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U
Acar
H V
HV
Ozkan
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S
Top
C
C
Nalbant
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S
Cermik
H
H
Cankir
Z
Z
Danaci
M
M
D000082:Acetaminophen / Q000633:toxicity*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000077604:Fomepizole; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000097:blood
D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D011720:Pyrazoles; D000082:Acetaminophen; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000637:Transaminases; D000111:Acetylcysteine