Ultrastructural Changes in the Kidneys and Biochemical Parameters of Blood and Urine in Rats under Acute Intoxication with O,O-Diethyl O-(4-nitrophenyl) Phosphate

Pesticides based on organophosphorus compounds (OPCs) are widely used in agriculture worldwide, which is fraught with acute and chronic human poisoning. In general, toxic effects of OPCs on the mammalian organism are well studied, but many etiological aspects of immediate and long-term consequences of poisoning require additional attention. The aim of this study was to assess the dynamics of biochemical blood and urine parameters along with pathomorphological and ultrastructural changes in the kidneys after acute poisoning of experimental rats with O-O-diethyl O-(4-nitrophenyl) phosphate (Paraoxon-ethyl, DNPP). The study was carried out on white outbred male rats Rattus norvegicus weighing 200–250 g. DNPP was injected to animals of experimental groups at a median lethal dose (LD50, single injection). Blood serum and urine samples for biochemical analysis and kidney tissue samples for morphological examination were taken on days 1, 3 and 7 after poisoning. Daily diuresis and urine specific gravity, as well as serum and urine levels of bilirubin, total protein, glucose, pH, creatinine, albumin, D-3-hydroxybutyrate and uric acid, were assessed. Pathomorphological changes in kidney tissue were documented. After DNPP exposure, there were observed a decrease in albumin and an increase in uric acid, glucose and D-3-hydroxybutyrate serum levels, as well as a decrease in the volume of daily diuresis and urine pH, paralleled by an increase in urine specific gravity. Morphological analysis of kidney tissue revealed a damage to epithelial cells of the proximal convoluted tubules and an increase in the thickness of glomerular basement membranes, respectively, 1 and 7 days after DNPP exposure. A single sublethal dose of DNPP had a nephrotoxic effect, as manifested in changes in biochemical blood and urine parameters, as well as morphological parameters of kidney tissue. The most pronounced changes in biochemical parameters were recorded 1 day after DNPP exposure, indicative of a decrease in the excretory capacity of the kidneys and the development of metabolic ketoacidosis. The thickening of glomerular basal membranes 7 days after exposure suggests the prerequisites for the formation of delayed pathology.