Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Egypt.
Ann Hepatol. 2009 Oct-Dec;8(4):364-70.
The present study was conducted to investigate effect of pentoxifylline (PTX) on acute liver injury caused by galactosamine (D-Gal) in rats and the underlying mechanism involved in this setting. Moreover, we attempted to compare its effect to the well-established hepatoprotective agent, silymarin (SYM). The rats were randomly assigned 5 groups, control, PTX-treated (100 mg/kg, 3 weeks), SYM-treated (100 mg/kg, 3 weeks) and their combination. Hepatic injury was induced by intraperitoneal single dose injection of D-Gal (800 mg/kg). Hepatic functions parameters, including serum albumin and alkaline phosphatase (ALP) levels were determined. Antioxidants enzyme activities such as superoxide dismutase (SOD), catalase (CAT) as well as lipid peroxides and hepatic total nitrites were measured. Besides, histopathological examination was also performed using portions of liver tissues. Results showed that the liver injury induced by D-Gal was improved in the three pretreated groups to variable extents. Pretreatment with PTX prevented D-Gal-induced reduction of antioxidant enzyme activities, SOD and CAT, and attenuated the elevated malonaldahyde (MDA) level in hepatic tissue as marker of lipid peroxidation. In addition, pretreatment with PTX resulted in an increase in hepatic triglycerides, normalization of nitric oxide level, and lowering serum ALP activity as well as inhibited the decreased serum albumin level caused by D-Gal. These biochemical changes were reflected on attenuation the structural alterations of the liver integrity. Collectively, our data suggest that PTX exhibits a potential hepatoprotective effect against D-Gal-induced hepatotoxicity and this effect might be attributed to its antioxidant properties.
本研究旨在探讨己酮可可碱(PTX)对 D-半乳糖胺(D-Gal)诱导的大鼠急性肝损伤的影响及其作用机制,并与已被证实的保肝药物水飞蓟素(SYM)进行比较。将大鼠随机分为 5 组:对照组、PTX 治疗组(100mg/kg,3 周)、SYM 治疗组(100mg/kg,3 周)及其联合治疗组。通过腹腔单次注射 D-Gal(800mg/kg)诱导肝损伤。测定血清白蛋白和碱性磷酸酶(ALP)水平等肝功能参数。测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)等抗氧化酶活性以及肝组织丙二醛(MDA)、总亚硝酸盐水平。此外,还对肝组织部分进行了组织病理学检查。结果表明,三种预处理组均不同程度地改善了 D-Gal 诱导的肝损伤。PTX 预处理可防止 D-Gal 诱导的抗氧化酶活性、SOD 和 CAT 降低,并减轻肝组织丙二醛(MDA)水平升高,提示脂质过氧化。此外,PTX 预处理可导致肝组织甘油三酯升高、一氧化氮水平正常化、血清 ALP 活性降低以及抑制 D-Gal 引起的血清白蛋白水平降低。这些生化变化反映了对肝完整性结构改变的抑制作用。综上所述,本研究数据表明,PTX 对 D-Gal 诱导的肝毒性具有潜在的保肝作用,其作用机制可能与其抗氧化特性有关。