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KMID : 0617220030140010231
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Duksung Bulletin Phamaceutical Sciences
2003 Volume.14 No. 1 p.231 ~ p.237
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Synthesis of Allylthiopyridazine Derivatives and Inhibition of Aflatoxin B_(1)-Induced Hepatotoxicity in Rats
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Shin Hea-Soon
Kwon Soon-Kyoung
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Abstract
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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㎎/㎏ 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㎎/㎏, three times at intervals of 3 days, i.p., or at 3㎎/㎏, once at final days, i.p.) administration were showed the significantly normal as compared with control in body and liver weights. Aspartate aminotrasnferase 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.
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