Fregnan G B, Frigerio L, Porta R, Prada M, Ruggieri F
Int J Tissue React. 1982;4(4):309-18.
The data presently reported show that repeated exposure of rats to allyl alcohol, ethionine or alpha-naphthyl isothiocyanate (ANIT) impaired some plasmatic parameters mainly by means of different mechanisms which involve the liver function. In particular, four administrations of allyl alcohol, given every other day, increased glutamate oxaloacetate transaminase (GOT) for at least 48 hours from the last dose; ethionine reduced the bromsulphthalein (BSP) clearance even after 48 hours from the 1st, 2nd, or 3rd administration given on the 1st, 5th, or 12th day; ANIT, administered daily for seven days, increased glutamate pyruvate transaminase (GPT), alkaline phosphatase (AP), bilirubin, triglycerides (TG) and cholesterol (CH) while it decreased the body-weight and retarded growth for at least six to seven days after intoxication. Twice daily administrations of dihydroxy-dibutylether (DHBE), a strong choleretic agent, brought to normality the parameters impaired by the three hepatointoxicating agents even when the intoxication was already established. In fact, DHBE reduced the plasma GOT levels increased by allyl alcohol, improved the BSP clearance impaired by ethionine and tended to normalize the parameters modified by ANIT by lowering GPT, AP, CH, TG and bilirubin plasma levels and by enhancing body growth. The curative activity of DHBE does not seem to be related only to a membrane stabilizing action since silymarin, a known cell membrane stabilizer, does not significantly influence the parameters described above in all the experimental conditions. Even the choleretic activity of DHBE alone might not be sufficient to explain its hepatoprotective action since fenipentol (a known choleretic agent) is inactive at least after ANIT intoxication.
目前报告的数据显示,大鼠反复接触烯丙醇、乙硫氨酸或α-萘基异硫氰酸酯(ANIT)主要通过涉及肝功能的不同机制损害了一些血浆参数。具体而言,每隔一天给予四次烯丙醇,从最后一剂起至少48小时内谷氨酸草酰乙酸转氨酶(GOT)升高;乙硫氨酸在第1、5或12天给予第1、2或3次给药后48小时,甚至降低了溴磺酞(BSP)清除率;连续七天每日给予ANIT,增加了谷氨酸丙酮酸转氨酶(GPT)、碱性磷酸酶(AP)、胆红素、甘油三酯(TG)和胆固醇(CH),同时在中毒后至少六至七天降低了体重并阻碍了生长。每日两次给予强利胆剂二羟基二丁醚(DHBE),即使中毒已经确立,也能使三种肝毒性药物损害的参数恢复正常。事实上,DHBE降低了烯丙醇升高的血浆GOT水平,改善了乙硫氨酸损害的BSP清除率,并倾向于通过降低GPT、AP、CH、TG和血浆胆红素水平以及促进身体生长使ANIT改变的参数恢复正常。DHBE的治疗活性似乎不仅仅与膜稳定作用有关,因为已知的细胞膜稳定剂水飞蓟素在所有实验条件下对上述参数均无显著影响。即使单独的DHBE的利胆活性也可能不足以解释其肝保护作用,因为芬尼戊醇(一种已知的利胆剂)至少在ANIT中毒后无活性。