Mera E, Muriel P, Castillo C, Mourelle M
Departamento de Farmacologia y Toxicologia, Centro de Investigacion y de Estudios Avanzados, D.F. Mexico.
J Appl Toxicol. 1994 Mar-Apr;14(2):87-90. doi: 10.1002/jat.2550140205.
Liver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3.). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4-induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg-1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, gamma-GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co-treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes.
四氯化碳（CCl4）所致的肝损伤取决于肝脏细胞色素P450酶系统将其代谢为高反应性中间体（CCl3·）的过程。西咪替丁会损害细胞色素P450，并刺激作用于DNA合成的再生过程。开展本研究是为了探究西咪替丁是否可以预防CCl4诱导的肝硬化。使用雄性Wistar大鼠：第1组动物每周腹腔注射3次CCl4（每100 g体重0.04 g），持续8周；第2组动物每周腹腔注射3次CCl4（每100 g体重0.04 g）加口服西咪替丁（120 mg/kg），持续8周；第3组动物先接受8周的CCl4注射，然后接受4周的西咪替丁治疗。检测血清中的碱性磷酸酶、γ-谷氨酰转肽酶（γ-GTP）和丙氨酸转氨酶（ALT）活性，以及蛋白质和胆红素水平；对肝脏中的胶原蛋白和脂质过氧化进行定量分析。CCl4中毒会使血清碱性磷酸酶、γ-GTP和ALT活性以及胆红素浓度升高（P < 0.05）；肝脏胶原蛋白和脂质过氧化也会增加。西咪替丁治疗可预防或逆转这三种酶活性以及胆红素含量的升高和蛋白质含量的下降。值得注意的是，西咪替丁联合治疗完全预防了胶原蛋白含量的增加和脂质过氧化。西咪替丁的保护作用可能归因于细胞色素P450的减少。然而，它也可能刺激再生过程。
