Synthesis of allylthiopyridazine derivatives and inhibition of aflatoxin B1-induced hepatotoxicity in rats.
Five kinds of allylthiopyridazine derivatives were synthesized and their chemoprotective activities examined in rats exposed to aflatoxin B1-toxicant. Rats were pretreated with five allylthiopyridazine derivatives at daily oral doses of 50 mg/kg for 10 consecutive days, and during this period with one or three repeated doses of the potent hepatotoxin, aflatoxin B1. The hepatoprotective effects of the allylthiopyridazine derivatives against aflatoxin B1 (1 mg/kg, three times at intervals of 3 days, i.p., or at 3 mg/kg, once at final days, i.p.) administration were showed the significantly normal as compared with control in body and liver weights. Aspartate aminotransferase and alanine aminotransferase levels were markedly elevated after aflatoxin B1 administration, and pretreatment with allylthiopyridazine derivatives, before aflatoxin B1 administration, resulted in decreased levels of these enzymes. In addition, the allylthiopyridazine derivatives, K6 (3-methoxy-), K8 (3-chloro-), K16 (3-ethoxy-) and K17 (3-n-propoxy), induced elevated hepatic GSH levels. Four kinds of allylthiopyridazine derivatives investigated were effective against aflatoxin B1-induced hepatotoxicity.
Shin
Hea-Soon
HS
College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea. hsshin@duksung.ac.kr
Kwon
Soon-Kyoung
SK
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000498:Allyl Compounds; D011724:Pyridazines; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase