Hagmann W, Steffan A M, Kirn A, Keppler D
Hepatology. 1987 Jul-Aug;7(4):732-6. doi: 10.1002/hep.1840070419.
The role of leukotrienes was investigated in frog virus 3-induced hepatitis in rats. Frog virus 3 elicited an enhanced generation of cysteinyl leukotrienes in vivo as monitored by measurement of N-acetyl-leukotriene E4 as the major endogenous metabolite of cysteinyl leukotrienes secreted into rat bile. N-Acetyl-leukotriene E4 concentrations were elevated for more than 4 hr after frog virus 3 injection. In vitro experiments using cultured rat liver Kupffer cells of high purity indicated that these cells can produce and metabolize leukotrienes and are thus a possible source of leukotrienes elicited in vivo by frog virus 3. The selective 5-lipoxygenase inhibitor AA 861 and the dual inhibitor of arachidonate lipoxygenase and cyclooxygenase, BW 755C, reduced the hepatocellular injury after a high dose of frog virus 3 by about 50 and 80%, respectively, as judged from plasma activities of ALT and sorbitol dehydrogenase at 24 hr after frog virus 3 administration. Our in vivo and in vitro studies argue in favor of an important role of leukotrienes as mediators in frog virus 3 hepatitis in rats.
研究了白三烯在蛙病毒3诱导的大鼠肝炎中的作用。通过测量N-乙酰白三烯E4（作为分泌到大鼠胆汁中的半胱氨酰白三烯的主要内源性代谢产物）来监测，蛙病毒3在体内引发了半胱氨酰白三烯生成的增加。注射蛙病毒3后，N-乙酰白三烯E4浓度升高超过4小时。使用高纯度培养的大鼠肝库普弗细胞进行的体外实验表明，这些细胞可以产生和代谢白三烯，因此是蛙病毒3在体内引发的白三烯的一个可能来源。从蛙病毒3给药后24小时的血浆丙氨酸转氨酶（ALT）和山梨醇脱氢酶活性判断，选择性5-脂氧合酶抑制剂AA 861以及花生四烯酸脂氧合酶和环氧化酶双重抑制剂BW 755C，分别使高剂量蛙病毒3后的肝细胞损伤降低了约50%和80%。我们的体内和体外研究表明，白三烯作为介质在蛙病毒3诱导的大鼠肝炎中起重要作用。
