Zim M C A, Silveira T R, Schwartsmann G, Cerski T, Motta A
Hospital da Criança Santo Antônio, Santa Casa de Misericórdia de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Braz J Med Biol Res. 2002 Nov;35(11):1339-46. doi: 10.1590/s0100-879x2002001100012.
Few data are available in the literature regarding the effect of pentosan polysulfate (PPS) on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl4) has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl4 for the induction of liver fibrosis. The study consisted of four stages: 1) hepatic fibrosis induction with CCl4 (N = 36 rats); 2) evaluation of the effect of PPS on CCl4-induced hepatic fibrosis (N = 36 rats); 3) evaluation of the effect of higher doses of PPS in combination with CCl4 (N = 50 rats); 4) evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats) using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days) male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8% CCl4 (N = 36) developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8) and 1 mg/kg PPS (N = 8) 1 h after the administration of CCl4, but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45). PPS (40 mg/kg) alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks). This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl4 and high doses of PPS, which results in massive hepatic necrosis.
关于戊聚糖多硫酸盐（PPS）对正常和纤维化大鼠肝脏的影响，文献中可用的数据很少。此外，PPS与四氯化碳（CCl4）的联合应用目前尚未得到研究。本研究的目的是评估PPS对用CCl4处理或未处理以诱导肝纤维化的大鼠肝脏的影响。该研究包括四个阶段：1）用CCl4诱导肝纤维化（N = 36只大鼠）；2）评估PPS对CCl4诱导的肝纤维化的影响（N = 36只大鼠）；3）评估高剂量PPS与CCl4联合应用的效果（N = 50只大鼠）；4）使用戊巴比妥钠试验评估PPS是否存在酶诱导作用（N = 18只大鼠），该试验间接评估体内肝微粒体酶活性。使用体重180至220 g的成年（60至70天）雄性Wistar大鼠。所有接受0.5 ml 8% CCl4的动物（N = 36）均出现肝纤维化，8周后还出现了肝硬化。在CCl4给药后1小时给予5 mg/kg PPS（N = 8）和1 mg/kg PPS（N = 8），未观察到肝纤维化的延迟或预防，但两种物质联合导致的肝毒性增加在大多数大鼠（N = 45）中引起了大规模肝坏死。单独使用PPS（40 mg/kg）仅在8周后导致肝充血，但在治疗1至4周后与0.5 ml CCl4联合时再次观察到大规模肝坏死。出乎意料的是，睡眠时间随着PPS给药时间（1、2或3周）的增加而延长。这表明PPS不作为肝微粒体酶系统的激活剂。有必要进行进一步研究，以阐明CCl4与高剂量PPS联合导致的意外肝毒性增加，这会导致大规模肝坏死。
