Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamilnadu, India.
Chem Biol Interact. 2010 Jul 30;186(2):200-10. doi: 10.1016/j.cbi.2010.03.028. Epub 2010 Mar 20.
The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin-nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-alpha, IL-1 beta, IL-6, NF-kappaB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.
本研究旨在通过测量氧化应激程度和肝组织中促炎细胞因子和抗氧化能力的水平，研究白藜芦醇在避免高血糖介导的氧化应激中的肝保护作用。在 30 天的实验期后，除了血清胆红素和肝天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）等生理病理标志物外，还研究了对照组和实验组大鼠肝组织中的 TNF-α、IL-1β、IL-6、NF-κB p65 和一氧化氮（NO）水平。测定了肝组织中的维生素 C、维生素 E 和还原型谷胱甘肽（GSH）的水平以及超氧化物歧化酶（SOD）、过氧化氢酶、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽-S-转移酶（GST）和谷胱甘肽还原酶（GR）的活性。还通过肝脂质过氧化物、氢过氧化物和蛋白质羰基来评估氧化应激程度。一部分肝脏用于组织学和超微结构研究。给糖尿病大鼠口服白藜芦醇（5mg/kg b.w.）可显著降低肝促炎细胞因子的水平，并显著减轻肝脂质过氧化物、氢过氧化物和蛋白质羰基的水平。糖尿病大鼠肝酶抗氧化剂活性的降低以及肝非酶抗氧化剂水平的降低，通过白藜芦醇给药恢复到接近正常水平。此外，组织学和超微结构观察结果表明，白藜芦醇通过减轻高血糖介导的氧化应激和抗氧化能力的标志物，有效地保护肝细胞免受氧化损伤，而不影响其细胞功能和结构完整性。本研究的结果表明，白藜芦醇通过减轻糖尿病大鼠肝组织中高血糖介导的氧化应激和抗氧化能力的标志物，具有肝细胞保护作用。
