BIOLOGICAL MARKERS AND MORPHOGENESIS OF ACUTE RENAL INJURY IN RAT DICHLOROETHANE POISONING

Author:

Sivak K. V.1,Savateeva-Lyubimova T. N.1,Gus’kova T. A.2,Kul’bitzkiy G. N.3,Alexandrova M. L.3

Affiliation:

1. Smorodintsev Research Institute of Influenza, Ministry of Healthcare of the Russian Federation

2. M.V. Dorogov Yaroslavl Center for Transfer of Pharmaceutical Technologies, K.D. Ushinsky Yaroslavl State Pedagogical University

3. Institute of Toxicology of the Federal Medical Biological Agency

Abstract

The article presents the results of an experimental study on rat poisoning with 1,2-dichloroethane (250 µl / kg, intragastric administration). The aim of this work was to find the relationship between biological markers and morphological changes in acute damage to rat kidneys with dichloroethane. The study of urine samples of experimental animals by gas-liquid chromatography (GLC) revealed 1,2-dichloroethane in the concentration range of 0,05 – 0,90 µg / ml (95% C.I. = 0,09 – 0,90 µg / ml). Daily excretion with urine was 0,60 – 4,50 µg / 16h (95% C.I. = 1,14 – 3,93 µg / ml). Levels of nephron-specific biomarkers in urine were 194,62 ± 9,02 IU / L (NAGase, p = 0,0022) and 2,93 ± 0,38 ng / ml (KIM-1, p = 0,0022), which exceeded those in the control group by 5 and 23 times, respectively. Edema, disorders of intrarenal hemodynamics, leukocyte migration in interstitium, uneven damage to various areas of the kidneys due to adipose dystrophy and necrobiotic changes in the nephrothelium of the proximal tubules mainly in the cortical layer of the kidneys have developed in the kidneys. Positive correlations between the level of 1,2-dichloroethane in the urine and the level of KIM-1 (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0,0083), -N-acetylglucosaminidase (Spearman r = 0,8248, 95% C.I. 0,4613 – 0,9512, p = 0,0019), the scores on the EGTI scale (Spearman r = 0,8064, 95% C.I. 0,7126 – 0,8719, p < 0.0001); the level of KIM-1 and the scores on the EGTI scale (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0.0083), -N-acetylglucosaminidase and the scores on the EGTI scale (Spearman R = 0,4684, 95% C.I. 0,2764 – 0,6244, p < 0,0001), the level of the low and medium molecular weight substances in the blood and the scores on the EGTI scale (Spearman R = 0,6909, 95% C.I. 0,5549 – 0,7909, p < 0,0001) were found.

Publisher

Russian Register of Potentially Hazardous Chemical and Biological Substances

Reference10 articles.

1. Kashtanova I.S., Elk D.P., Fedotova I.N. Acute poisoning with dichloroethane (clinical observations) // Trudnyy patsiyent №6, T.12, 2014. P. 48-52 (in Russian)

2. Bushuyev Ye.S., Basharin V.A., Gorbachova T.V., Fokin M.B. Volatile organic compounds: chemical-toxicological analysis. – SPb.: OOO «Izdatel’stvo «Levsha. Sankt-Peterburg», 2018. – 240 P. (in Russian)

3. Mehendale H.M. Halogenated Hydrocarbons // Compr. Toxicol. 2010. С. 459–474.

4. Bonitenko, Yu.Yu., Bonitenko, E.Yu. Ethanol and toxicity of 1,2-dichloroethane // Medline. – 2003. – T.4. – P. 451-460 (in Russian)

5. Yermolenko V.M., Nikolaev A.D. Acute renal failure. – Moscow: GEOTAR-Media, 2010. – 240 P. (in Russian)

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