Yaman Halil, Cakir Erdinc, Akgul Emin O, Aydin Ibrahim, Onguru Onder, Cayci Tuncer, Kurt Yasemin Gulcan, Agilli Mehmet, Aydin Fevzi N, Gulec Mustafa, Altinel Ozcan, Isbilir Salim, Ersoz Nail, Yasar Mehmet, Turker Turker, Bilgi Cumhur, Erbil Kemal M
Department of Medical Biochemistry, Gulhane Military Medical Academy, Etlik-06018 Ankara, Turkey.
Exp Toxicol Pathol. 2013 Jan;65(1-2):147-51. doi: 10.1016/j.etp.2011.07.003. Epub 2011 Aug 30.
Overdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury.
Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups.
APAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared with control group (7.5±3.3 ng/mg protein), mean liver PTX-3 concentrations were 14.1±3.0 (p=0.032) and 28.5±8.2 (p<0.001) ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p<0.001 and p<0.001, respectively).
PTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury.
对乙酰氨基酚（APAP）过量可导致人类和实验动物严重肝损伤。多种细胞类型可产生并释放五聚体3（PTX-3）。在本研究中，我们旨在评估PTX-3是否为鉴定APAP诱导的肝损伤的潜在生物标志物。
30只成年雄性Wistar大鼠随机分为三组：对照组、APAP-1组和APAP-2组。APAP-1组（1 g/kg）和APAP-2组（2 g/kg）大鼠经胃管给予APAP。获取肝组织和血样进行生化和组织病理学分析。测定所有组的生化参数、血浆和肝脏PTX-3水平以及肝坏死程度。
APAP处理导致肝脏坏死，并在48小时后伴有肝脏PTX-3水平升高。与对照组（7.5±3.3 ng/mg蛋白）相比，APAP-1组和APAP-2组肝脏PTX-3平均浓度分别为14.1±3.0（p=0.032）和28.5±8.2（p<0.001）ng/mg蛋白。APAP-2组所有大鼠（100%）出现3级肝坏死。然而，APAP-1组分别有10%、40%和50%的大鼠出现1级、2级和3级肝坏死。APAP-1组和APAP-2组的肝坏死程度高于对照组（分别为p<0.001和p<0.001）。
PTX-3可能在大鼠APAP诱导的肝损伤中起作用。APAP诱导的肝坏死中肝脏PTX-3升高可能是急性组织学肝损伤的标志物。有必要进行进一步的前瞻性研究以阐明肝脏PTX-3对预测APAP诱导的肝损伤中组织学肝坏死的预后价值。
