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Synthesis of Allylthiopyridazine Derivatives and Inhibition of Aflatoxin ${B_1}-Induced$ Hepatotoxicity in Rats  

Shin, Hea-Soon (College of Pharmacy, Duksung Women s University)
Kwon, Soon-Kyoung (College of Pharmacy, Duksung Women s University)
Publication Information
Archives of Pharmacal Research / v.26, no.5, 2003 , pp. 351-357 More about this Journal
Abstract
Five kinds of allylthiopyridazine derivatives were synthesized and their chemoprotective activities examined in rats exposed to aflatoxin $B_1$-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 $B_1$. The hepatoprotective effects of the allylthiopyridazine derivatives against aflatoxin $B_1$ (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 $B_1$ administration, and pretreatment with allylthiopyridazine derivatives, before aflatoxin $B_1$ 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 $B_1$ -induced hepatotoxicity.
Keywords
Allylthiopyridazine derivatives; Aflatoxin ${B_1}-induced$ hepatotoxicity; Hepatoprotective effect;
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