New biomarkers for 1,1-dimethylhydrazine

Abstract

Introduction. Despite the large-scale use of asymmetric dimethylhydrazine (UDMH) in the domestic rocket and space industry, its biomarkers of exposure in blood plasma and urine, as well as biomarkers of cardiotoxic effects, have not yet been described. Material and methods. The study of blood and urine samples of rats after a single injection of 10 mg/kg UDMH (1/16 LD50) was carried out by HPLC-MS. The determination of the non-metabolized form of UDMH was also carried out using the method of gas chromatography with mass-selective detection with preliminary derivatization with 4-pyridinecarboxyaldehyde. The cardiotoxic effect of UDMH was assessed on a model of an isolated rat heart with subchronic intragastric administration for 28 days at doses of 0,02; 0,2; 2,0 mg/kg. Results. It has been established that the main metabolites of UDMH are dimethylhydrazones of pyridoxal (vitamin B6) and pyruvic acid (pyruvate). The possibility of determining the non-metabolized form of UDMH in blood and urine by HPLC-MS was shown, concentrations reach 10-60 ng/ml of blood plasma and 200-2000 ng/ml. The use of UDMH leads to an increase in the mass coefficient of the heart at a dose of 2,0 mg/kg. In ex vivo experiments on the rat heart, the cardiotoxic effect of UDMH was shown at subchronic use at a dose of 0,2 mg/kg and above, expressed in significant dilatation of the coronary bloodstream and left ventricle, the development of pronounced negative inotropic and chronotropic effects, and a decrease in the maximum rate of contraction and relaxation of the left ventricle. ventricle, reflecting the inhibition of myocardial energy metabolism. Limitations of the study. In the work, biomarkers were detected after a single intragastric injection of NDMG, the toxicokinetic characteristics of biomarkers and their retrospectivity were not evaluated. Conclusion. The main metabolites of UDMH with intravenous administration of 1/16 DL50 are dimethylhydrazones of pyridoxal (vitamin B6) and pyruvic acid (pyruvate). With subchronic administration, UDMH has cardiotoxicity at a dose of 0,02 mg/kg and above.