Sehirli Ozer, Ozel Yahya, Dulundu Ender, Topaloglu Umit, Ercan Feriha, Sener Goksel
Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
Phytother Res. 2008 Jan;22(1):43-8. doi: 10.1002/ptr.2256.
This study was designed to determine the possible protective effect of grape seed extract (GSE), a widely used antioxidant dietary supplement, on hepatic ischemia/reperfusion (I/R) injury. Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by a 60 min reperfusion period. GSE was administered in a dose of 50 mg/kg/day orally for 15 days before I/R injury and repeated before the reperfusion period. Liver samples were taken for histological examination or determination of hepatic malondialdehyde (MDA), glutathione (GSH) and myeloperoxidase (MPO) activity. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Lactate dehydrogenase (LDH) and cytokines (TNF-alpha and IL-1 beta) were also assayed in serum samples for the evaluation of generalized tissue damage. Ischemia/reperfusion caused a significant decrease in hepatic GSH, and significant increases in MDA level, and MPO activity. Serum AST and ALT levels, as well as LDH activity and plasma TNF-alpha and IL-1beta levels were also elevated in the I/R group. Treatment with GSE reversed all these biochemical parameters as well as histological alterations induced by I/R. In conclusion, GSE reduced I/R-induced organ injury through its ability to balance the oxidant-antioxidant status, to inhibit neutrophil infiltration and to regulate the release of inflammatory mediators.
本研究旨在确定葡萄籽提取物(GSE)这一广泛使用的抗氧化膳食补充剂对肝脏缺血/再灌注(I/R)损伤可能的保护作用。将Wistar白化大鼠进行45分钟的肝脏缺血,随后进行60分钟的再灌注期。在I/R损伤前15天,以50毫克/千克/天的剂量口服给予GSE,并在再灌注期前重复给药。采集肝脏样本进行组织学检查或测定肝脏丙二醛(MDA)、谷胱甘肽(GSH)和髓过氧化物酶(MPO)活性。测定血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平以评估肝功能。还检测血清样本中的乳酸脱氢酶(LDH)和细胞因子(TNF-α和IL-1β)以评估全身性组织损伤。缺血/再灌注导致肝脏GSH显著降低,MDA水平和MPO活性显著升高。I/R组的血清AST和ALT水平以及LDH活性和血浆TNF-α和IL-1β水平也升高。GSE治疗逆转了所有这些生化参数以及I/R诱导的组织学改变。总之,GSE通过平衡氧化还原状态、抑制中性粒细胞浸润和调节炎症介质释放的能力减轻了I/R诱导的器官损伤。