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.

中文翻译：

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大鼠肝癌形成过程中氧化应激的24小时节律：褪黑素或α-酮戊二酸的作用。

为了比较α-酮戊二酸酯（alpha-KG）和褪黑激素对注射N-亚硝基二乙胺（NDEA）的Wistar雄性大鼠褪黑素（5 mg / kg ip）或alpha-KG（2的氧化应激的节律性的影响）2每天通过胃内导管输注1 g / kg，持续20周。在24小时内的6个时间点采集的血液中，测定了天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的血清活性以及甲胎蛋白（alpha-FP）的水平，作为肝功能的标志物。为了评估脂质过氧化和抗氧化剂状态，测量了血浆硫巴比妥酸反应性物质（TBARS）和还原型谷胱甘肽（GSH）的水平，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）的活性）和谷胱甘肽S-转移酶（GST）。NDEA增强了AST和ALT活性的节律和节律幅度，血浆α-FP水平和血浆TBARS的测定值，同时降低了血浆GSH和红细胞SOD，CAT，GPx和GST的测定值。除α-FP节律外，其他所有情况下NDEA均延迟了顶生相的发展。褪黑激素或α-KG的共同给药部分抵消了NDEA的作用。褪黑素降低了血浆TBARS的膜并增加了SOD活性。结果表明，褪黑激素和α-KG可以有效地防止NDEA诱导的氧化应激24小时节律的紊乱。褪黑素增强了大鼠的抗氧化防御能力。除α-FP节律外，其他所有情况下NDEA均延迟了顶生相的发展。褪黑激素或α-KG的共同给药部分抵消了NDEA的作用。褪黑素降低了血浆TBARS的膜并增加了SOD活性。结果表明，褪黑激素和α-KG可以有效地防止NDEA诱导的氧化应激24小时节律的紊乱。褪黑素增强了大鼠的抗氧化防御能力。除α-FP节律外，其他所有情况下NDEA均延迟了顶生相的发展。褪黑激素或α-KG的共同给药部分抵消了NDEA的作用。褪黑素降低了血浆TBARS的膜并增加了SOD活性。结果表明，褪黑激素和α-KG可以有效地防止NDEA诱导的氧化应激24小时节律的紊乱。褪黑素增强了大鼠的抗氧化防御能力。结果表明，褪黑激素和α-KG可以有效地防止NDEA诱导的氧化应激24小时节律的紊乱。褪黑素增强了大鼠的抗氧化防御能力。结果表明，褪黑激素和α-KG可以有效地防止NDEA诱导的氧化应激24小时节律的紊乱。褪黑素增强了大鼠的抗氧化防御能力。