Subramanian Perumal, Dakshayani Kadiyala Babu, Pandi-Perumal Seithikurippu R, Trakht Ilya, Cardinali Daniel P
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.
Redox Rep. 2008;13(2):78-86. doi: 10.1179/135100008X259178.
To compare the effects of alpha-ketoglutarate (alpha-KG) and melatonin on 24-h rhythmicity of oxidative stress in N-nitrosodiethylamine (NDEA)-injected Wistar male rats, melatonin (5 mg/kg i.p.) or alpha-KG (2 g/kg through an intragastric tube) was given daily for 20 weeks. In blood collected at 6 time points during a 24-h period, serum activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein (alpha-FP) were measured as markers of liver function. To assess lipid peroxidation and the antioxidant status, plasma levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured, together with the activity of erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). NDEA augmented mesor and amplitude of rhythms in AST and ALT activity and plasma alpha-FP levels and mesor values of plasma TBARS, while decreasing mesor values of plasma GSH and erythrocyte SOD, CAT, GPx and GST. Acrophases were delayed by NDEA in all cases except for alpha-FP rhythm, which became phase-advanced. Co-administration of melatonin or alpha-KG partially counteracted the effects of NDEA. Melatonin decreased mesor of plasma TBARS and augmented mesor of SOD activity. The results indicate that melatonin and alpha-KG are effective in protecting from NDEA-induced perturbation of 24-h rhythms in oxidative stress. Melatonin augmented antioxidant defense in rats.
为比较α-酮戊二酸（α-KG）和褪黑素对注射N-亚硝基二乙胺（NDEA）的Wistar雄性大鼠氧化应激24小时节律性的影响，每天腹腔注射褪黑素（5 mg/kg）或经胃管给予α-KG（2 g/kg），持续20周。在24小时内的6个时间点采集血液，检测血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性以及甲胎蛋白（α-FP）水平作为肝功能指标。为评估脂质过氧化和抗氧化状态，检测血浆中硫代巴比妥酸反应性物质（TBARS）和还原型谷胱甘肽（GSH）水平，以及红细胞超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽S-转移酶（GST）的活性。NDEA增加了AST和ALT活性以及血浆α-FP水平的节律中值和振幅，以及血浆TBARS的中值，同时降低了血浆GSH以及红细胞SOD、CAT、GPx和GST的中值。除α-FP节律提前外，NDEA使所有指标的峰相位延迟。联合给予褪黑素或α-KG可部分抵消NDEA的作用。褪黑素降低了血浆TBARS的中值并增加了SOD活性。结果表明，褪黑素和α-KG可有效保护机体免受NDEA诱导的氧化应激24小时节律紊乱。褪黑素增强了大鼠的抗氧化防御能力。
