Pradeep Kannampalli, Park Sang Hyun, Ko Kyong Cheol
Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, 1266 Shinjeong-dong, Jeongeup, Jeonbuk 580-185, Republic of Korea.
Eur J Pharmacol. 2008 Jun 10;587(1-3):273-80. doi: 10.1016/j.ejphar.2008.03.052. Epub 2008 Apr 4.
Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.w, orally) for 7 days post irradiation. The changes in body weight, liver weight, spleen index, serum and liver aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and serum ceruloplasmin levels were determined along with differences in the liver histopathology. Liver thiobarbuturic acid reactive substance as an index for lipid peroxidation and the levels of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and the status of non-enzymatic antioxidants as an index for oxidative stress were also determined. Exposure to gamma-irradiation resulted in hepatocellular damage in a dose-dependent manner, featuring a significantly decreased body weight and liver weight and higher levels of serum AST, ALT, ALP, LDH and gamma-GT levels and a simultaneous decrease in their levels in the liver tissue. Oxidative stress was evidenced by elevated levels of lipid peroxidation and a decrease in the levels of key enzymatic and non-enzymatic antioxidants in the liver. However, the gamma-irradiation induced toxic effects were dramatically and dose-dependently inhibited by hesperidin treatment as observed by the restoration in the altered levels of the marker enzymes, lipid peroxidation, enzymatic and non-enzymatic antioxidants. The results of the biochemical observations were supported by the histopathological findings. Thus, oral administration of hesperidin was found to offer protection against gamma-irradiation induced hepatocellular damage and oxidative stress in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging and membrane stabilizing ability.
氧化应激在γ射线诱导的细胞损伤的发病机制和进展中起关键作用,并且有人提出给予膳食抗氧化剂可预防随后的组织损伤。在此,我们展示数据以探究橙皮苷(一种天然存在的柑橘类黄酮糖苷)对γ射线诱导的大鼠肝脏氧化损伤的肝脏保护和抗氧化作用。将健康雄性Sprague-Dawley大鼠暴露于γ射线(1 Gy、3 Gy和5 Gy)下,并在照射后7天口服给予橙皮苷(50 mg/kg和100 mg/kg,体重)。测定体重、肝脏重量、脾脏指数、血清和肝脏中的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、γ-谷氨酰转肽酶(γ-GT)以及血清铜蓝蛋白水平的变化,同时观察肝脏组织病理学差异。测定肝脏中作为脂质过氧化指标的硫代巴比妥酸反应性物质以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶等酶促抗氧化剂的水平,以及作为氧化应激指标的非酶促抗氧化剂的状态。暴露于γ射线以剂量依赖性方式导致肝细胞损伤,表现为体重和肝脏重量显著降低,血清AST、ALT、ALP、LDH和γ-GT水平升高,同时肝脏组织中这些水平降低。脂质过氧化水平升高以及肝脏中关键酶促和非酶促抗氧化剂水平降低证明了氧化应激的存在。然而,如通过恢复改变的标志物酶水平、脂质过氧化、酶促和非酶促抗氧化剂水平所观察到的,橙皮苷处理显著且剂量依赖性地抑制了γ射线诱导的毒性作用。生化观察结果得到了组织病理学发现的支持。因此,发现口服橙皮苷可保护大鼠免受γ射线诱导的肝细胞损伤和氧化应激,这可能是通过其自由基清除和膜稳定能力对肝细胞坏死发挥保护作用。