Muthuvel Arumugham, Rajamani Rathinam, Manikandan Sundaramahalingam, Sheeladevi Rathinasamy
Department of Physiology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600113, TamilNadu, India.
Clin Chim Acta. 2006 May;367(1-2):162-9. doi: 10.1016/j.cca.2005.12.007. Epub 2006 Jan 27.
Formic acid is a toxic metabolite responsible for the metabolic acidosis in methanol poisoning. Formate dehydrogenase (EC 1.2.1.2) converts formate into CO2 in the presence of NAD. We examined the in vitro and in vivo efficiency of formate dehydrogenase-loaded carrier erythrocytes along with carbicarb in eliminating the formate in methanol-intoxicated folate-deficient rats.
Formate dehydrogenase-loaded erythrocytes were prepared by hypotonic dialysis method. Carbicarb (carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Folate depletion was induced by methotrexate (MTX) treatment. Experimental design consisted of 8 groups: saline control, methanol control, MTX control, ELE control, MTX-methanol control, MTX-methanol-carb, MTX-methanol-carb-ELE, and MTX-MeOH-ELE group. Male Wistar rats treated with MTX (0.3 mg/kg) for a week were injected (i.p.) with methanol (4 g/kg). Twelve hours later, the carbicarb solution was infused, and then a formate dehydrogenase-loaded erythrocytes suspension (40% hematocrit) was infused (i.v.) in bolus. Blood samples were collected every hour for 4 h from the cannulated left jugular vein. Blood methanol and formate were estimated respectively with HPLC and fluorimetric assay. Blood pH, blood pO2, pCO2 and bicarbonate were also measured.
There was marked elimination of formate in selected groups.
Formate dehydrogenase-loaded erythrocytes, along with carbicarb, facilitates removal of formate, in methanol poisoning.
甲酸是甲醇中毒所致代谢性酸中毒的一种有毒代谢产物。甲酸脱氢酶（EC 1.2.1.2）在烟酰胺腺嘌呤二核苷酸（NAD）存在的情况下将甲酸转化为二氧化碳。我们研究了负载甲酸脱氢酶的载体红细胞与卡比卡（一种等摩尔的碳酸钠和碳酸氢钠溶液）在消除甲醇中毒且叶酸缺乏大鼠体内甲酸方面的体内外效率。
通过低渗透析法制备负载甲酸脱氢酶的红细胞。卡比卡用于治疗代谢性酸中毒。通过甲氨蝶呤（MTX）处理诱导叶酸缺乏。实验设计包括8组：生理盐水对照组、甲醇对照组、MTX对照组、红细胞提取物（ELE）对照组、MTX - 甲醇对照组、MTX - 甲醇 - 卡比卡组、MTX - 甲醇 - 卡比卡 - ELE组和MTX - 甲醇 - ELE组。用MTX（0.3mg/kg）处理一周的雄性Wistar大鼠经腹腔注射甲醇（4g/kg）。12小时后，输注卡比卡溶液，然后静脉推注负载甲酸脱氢酶的红细胞悬液（血细胞比容为40%）。从插管的左颈静脉每小时采集一次血样，共采集4小时。分别用高效液相色谱法（HPLC）和荧光分析法测定血甲醇和甲酸。同时测量血液pH值、血氧分压（pO2）、二氧化碳分压（pCO2）和碳酸氢盐。
在选定的组中甲酸有显著消除。
负载甲酸脱氢酶的红细胞与卡比卡一起，有助于在甲醇中毒时清除甲酸。
