Affiliation:
1. A.A. Smorodintsev Research Institute of Influenza, RF Ministry of Healthcare, 197376, Saint Petersburg
2. M.V. Dorogov Yaroslavl Center for the Transfer of Pharmaceutical Technologies, K.D. Ushinsky Yaroslavl State Pedagogical University, 150010, Yaroslavl
Abstract
The article presents the results of the experimental toxicological study of rats poisoned with uranyl acetate dihydrate (300 mg / kg body weight). The aim of this study was to develop methodological approaches to the early detection of acute toxic kidney damage on the basis of the dynamics of some biomarkers on 1, 3 and 7 days after nephrotoxin administration. For renal biomarkers reflecting the value of glomerular filtration rate (creatinine in the blood, cutoff 112,77 µmol/l) the mechanism of cell death (TPA in urine, cutoff of 5.28 IU/ml), degenerative changes and regeneration (KIM-1 in urine, cutoff of 0.28 ng/ml; at values above 8,2 ng/ml the lethal effect can be expected), the inflammatory infiltration and the induction of tissue reparation (MCP-1 in urine, cutoff 11,70 pg/ml, TGF-β1 in the urine, cutoff 34,33 pg/ml), the sensitivity and specificity have been determined. According to the sequence of urine level increase, the studied biomarkers can be arranged in the following series: early stage – TPA; stage of necrosis growth and leukocyte infiltration – KIM-1, MCP-1, creatinine; stage of deep necrotic changes – TGF-β1. The studied markers are of interest for use as diagnostic tools in determining the stage of kidney disease in nephrotoxic poisoning.
Publisher
Russian Register of Potentially Hazardous Chemical and Biological Substances
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