Effect of Pre-treatment of α-Ketoglutarate on Cyanide-induced Toxicity and Alterations in Various Physiological Variables in Rodents  

作　　者：RAJKUMAR TULSAWANI DEO KUMAR R.BHATTACHARYA 

机构地区：[1]Division of Pharmacology and Toxicology Defence Research and Development Establishment Jhansi Road Gwalior 474 002 M.P. India

出　　处：《Biomedical and Environmental Sciences》2007年第1期56-63,共8页生物医学与环境科学（英文版）

摘　　要：Objective To investigate the effects of pre-treatment of α-ketoglutarate （α-KG） on cyanide-induced lethality and changes in various physiological parameters in rodents. Methods The LD50 of potassium cyanide （KCN） given orally （po）, intraperitoneally （ip）, subcutaneously （sc） or intravenously （iv） was determined in male mice, in the presence or absence α-KG given po, ip or iv. α-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index （PI） was calculated as the ratio of LD50 of KCN in the presence of α-KG （protected animals） and LD50 of KCN in the absence of α-KG （unprotected animals）. In a separate experiment, several physiological variables viz. mean arterial pressure （MAP）, heart rate （HR）, respiratory rate （RR）, neuromuscular transmission （NMT） and rectal temperature （RT） were measured in anesthetized female rats pre-treated （-10 rain） with po （2.0 g/kg） or iv （0.125 g/kg） α-KG and then administered sub-lethal （0.75 LD50） or lethal （2.0, 4.0 or 8.0 LD50） doses of KCN （po）. Results PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with α-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg α-KG given ip （-10 min）, respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg α-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg α-KG given po at -10, -20 or -40 rain, respectively. No appreciable protection was observed when lower doses of α-KG （ip or po） challenged KCN given by sc route. Pre-treatment of iv or po administration of α-KG did not afford any protection against KCN gObjective To investigate the effects of pre-treatment of α-ketoglutarate （α-KG） on cyanide-induced lethality and changes in various physiological parameters in rodents. Methods The LD50 of potassium cyanide （KCN） given orally （po）, intraperitoneally （ip）, subcutaneously （sc） or intravenously （iv） was determined in male mice, in the presence or absence α-KG given po, ip or iv. α-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index （PI） was calculated as the ratio of LD50 of KCN in the presence of α-KG （protected animals） and LD50 of KCN in the absence of α-KG （unprotected animals）. In a separate experiment, several physiological variables viz. mean arterial pressure （MAP）, heart rate （HR）, respiratory rate （RR）, neuromuscular transmission （NMT） and rectal temperature （RT） were measured in anesthetized female rats pre-treated （-10 rain） with po （2.0 g/kg） or iv （0.125 g/kg） α-KG and then administered sub-lethal （0.75 LD50） or lethal （2.0, 4.0 or 8.0 LD50） doses of KCN （po）. Results PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with α-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg α-KG given ip （-10 min）, respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg α-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg α-KG given po at -10, -20 or -40 rain, respectively. No appreciable protection was observed when lower doses of α-KG （ip or po） challenged KCN given by sc route. Pre-treatment of iv or po administration of α-KG did not afford any protection against KCN g

关 键 词：CYANIDE TOXICITY Physiological variables Protection Α-KETOGLUTARATE 

分 类 号：R363[医药卫生—病理学]