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Effect of α-Ketoglutarate on Cyanide-induced Biochemical Alterations in Rat Brain and Liver

查看全文 作　　者：RAJKUMAR [1]TULSAWANI;R. [1]BHATTACHARYA 高影响力作者 机构地区：[1]Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474002, (M. P.), India高影响力机构 出　　处：《Biomedical and Environmental Sciences》索引2006年第19卷第1期,共6页高影响力期刊 摘　　要：Objective To investigate the biochemical changes in rat brain and liver following acute exposure to a lethal dose of cyanide, and its response to treatment of α-ketoglutarate (α-KG) in the absence or presence of sodium thiosulfate (STS). Methods Female rats were administered 2.0 LD50 potassium cyanide (KCN; oral) in the absence or presence of pre-treatment (?10 min), simultaneous treatment (0 min) or post-treatment (+2-3 min) of α-KG (2.0 g/kg, oral) and/or STS (1.0 g/kg, intraperitoneal, ?15 min, 0 min or + 2-3 min). At the time of onset of signs and symptoms of KCN toxicity (2-4 min) and at the time of death (5-15 min), various parameters particularly akin to oxidative stress viz. cytochrome oxidase (CYTOX), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and oxidized glutathione (GSSG) in brain, and CYTOX, sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), GSH and GSSG in liver homogenate were measured. Results At both time intervals brain CYTOX, SOD, GPx, and GSH significantly reduced (percent inhibition compared to control) to 24%, 56%, 77%, and 65%, and 44%, 46%, 78%, and 57%, respectively. At the corresponding time points liver CYTOX and GSH reduced to 74% and 63%, and 44% and 68%, respectively. The levels of GSSG in the brain and liver, and hepatic ALP and SDH were unchanged. Pre-treatment and simultaneous treatment of α-KG alone or with STS conferred significant protection on above variables. Post-treatment was effective in restoring the changes in liver but failed to normalize the changes in the brain. Conclusions Oral treatment with α-KG alone or in combination with STS has protective effects on cyanide-induced biochemical alterations in rat brain and liver. 关 键 词：Α-酮戊二酸 氰化物 生物化学 肝脑疾病
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