비타민 A 및 피리딘으로 유발된 사염화탄수 유발성 간독성에 대한 2-(알릴티오)피라진의 보호효과: (phi)x-174 DNA 손상에 미치는 효과

• 영문명: Protective Effects of 2-(Allylthio)pyrazine on Retinoyl Palmitate- and Pyridine-Potentiated Carbon tetrachloride- induced Hepatotoxicity: Effect on (phi)x-174 DNA Strand Breakage
• 발행기관: 대한약학회
• 저자명: 김상건(Sang Geon Kim) 조주연(Joo Youn Cho) 최성희(Sung Hee Choi) 김낙두(Nak Doo Kim)
• 간행물 정보: 『약학회지』제40권 제6호 (1996년), 727~733쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1996.12.31

영문 초록

2-(Allylthio)pyrazine is effective in selectively suppressing constitutive and inducible expression of cytochrome P450 2E1. The effect of 2-(allylthio)pyrazine against potentiated chemical injury was studied in rats. Vitamin-A pretreatment of rats substantially increased carbon tetrachloride hepatotoxicity, as supported by an ~4-fold increase in serum alanine aminotransferase (ALT) activity. Concomitant pretreatment of rats with 2-(allylthio)pyrazine at the daily dose of 200mg/kg resulted in a 76% decrease in vitamin-A-potentiated hepatotoxicity, which supported the possibility that 2-(allylthio)pyrazine protects the liver against chemical-induced hepatic injury by the mechanism associated with Kupffer cell inactivation. Pyridine pretreatment caused substantial enhancement in carbon tetrachloride hepatotoxicity. 2-(Allylthio)pyrazine treatment of rats reduced the pyridine-potentiated toxicity in a dose-dependent manner. Animals treated with both pyridine and 2-(allylthio)pyrazine prior to intoxicating dose of CCl4 resulted in 85% and 47% decreases in pyridine-increased triglycerides and cholesterol levels in the liver. The protective effect of 2-(allylthio)pyrazine on the DNA strand breakage induced by benzenetriol was assessed by measuring the conversion of supercoiled (phi)x-174 DNA to the open relaxed form. 2-(Allylthio)pyrazine blocked the benzenetriol-induced conversion of supercoiled DNA to open circular form in a dose-dependent manner. The presence of 2-(allylthio)pyrazine at the doses from I to 10mM in the incubation mixture containing 5mcM benzenetriol completely protected benzenetriol-induced DNA strand breakage with the EC50 for the 2-(allylthio)pyrazine blocking being noted as ~220mcM, whereas allyl disulfide exerted protecting effect at relatively high concentrations (i.e. ~850mcM), suggesting that 2-(allylthio)pyrazine effectively scavenges the reactive oxygen species. These results provide evidence that 2-(allylthio)pyrazine blocks vitamin A- or pyridine-potentiated CCl4 hepatotoxicity and that the agent is active in protecting DNA by scavenging the reactive oxygen species.

키워드

2-{allyIthio)pyrazine hepatoprotective effect Kupffer cell hepatotoxicity.