Cavar Ivan, Kelava Tomislav, Heinzel Renata, Culo Filip
Department of Physiology, School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina.
Coll Antropol. 2009 Dec;33 Suppl 2:25-9.
Prostaglandins (PGs) are lipid compounds that mediate the variety of physiological and pathological functions in almost all body tissues and organs. Prostacyclin (prostaglandin 12, PGI2), which is synthesized by the vascular endothelium, is a potent vasodilator, inhibits the aggregation of platelets in vitro and has cytoprotective effect on gastrointestinal mucosa. The aim of this study was to determine whether PGI2 is playing a role in host defense to toxic effect of acetaminophen (APAP). This was investigated in C57Black/6 mice which were intoxicated with single lethal or high sublethal dose of APAP. APAP was administered to mice by gastric lavage and PGI2 agonists or antagonists were given intraperitoneally (i.p.) 30 minutes before or 2 hours after administration of APAP. The toxicity of APAP was determined by observing the survival of mice during 48 hours, by measuring the concentration of alanine-aminotransferase (ALT) in plasma 20-24 hours after APAP administration, and by liver histology. Mice were given either pure PGI2 (PGI2 sodium salt), its stable agonist (iloprost) or inhibitor of prostacyclin (IP)-receptor (CAY-10441). The results have shown that PGI2 exibits a strong hepatoprotective effect when it was given to mice either before or after APAP (both increase of survival of mice and decrease of plasma ALT levels were statistical significant). Iloprost has not shown a similar effect and CAY-10441 increased toxic effect of APAP if given 2 hours after its administration. Histopathological changes in liver generally support these findings. These investigations support the view that PGI2 is involved in defense of organism to noxious effects of xenobiotics on liver.
前列腺素（PGs）是一类脂质化合物，介导几乎所有身体组织和器官的多种生理和病理功能。前列环素（前列腺素I2，PGI2）由血管内皮合成，是一种强效血管舒张剂，在体外可抑制血小板聚集，对胃肠道黏膜具有细胞保护作用。本研究的目的是确定PGI2是否在宿主抵御对乙酰氨基酚（APAP）毒性作用的防御中发挥作用。这一作用在C57BL/6小鼠中进行了研究，这些小鼠被给予单次致死剂量或高亚致死剂量的APAP使其中毒。通过灌胃给小鼠施用APAP，并在施用APAP前30分钟或后2小时腹腔注射（i.p.）PGI2激动剂或拮抗剂。通过观察小鼠48小时内的存活情况、在施用APAP后20 - 24小时测量血浆中丙氨酸转氨酶（ALT）的浓度以及进行肝脏组织学检查来确定APAP的毒性。给小鼠分别给予纯PGI2（PGI2钠盐）、其稳定激动剂（伊洛前列素）或前列环素（IP）受体抑制剂（CAY - 10441）。结果表明，在APAP给药前或给药后给小鼠施用PGI2均表现出强大的肝保护作用（小鼠存活率增加和血浆ALT水平降低均具有统计学意义）。伊洛前列素未显示出类似效果，而如果在施用APAP后2小时给予CAY - 10441，则会增加APAP的毒性作用。肝脏的组织病理学变化总体上支持这些发现。这些研究支持了PGI2参与机体抵御外源性物质对肝脏有害作用的观点。
