Affiliation:
1. Institute of Biomedical Research – branch of Vladikavkaz Scientific Center of the Russian Academy of Sciences
Abstract
The aim of the work is to study pharmacological substances that play a role of eNOS expression regulators in the modification of lead intoxication effects in the experiment.Materials and methods. In the experiment, linear male rats of the same age were used: intact and with lead intoxication (120 heads). The study design was the following: group 1 – control; group 2 – intoxication with a lead acetate solution; group 3 – intact + L-nitroarginine methyl ester; group 4 – lead acetate + L-nitroarginine methyl ester; group 5 – intact + L-arginine; group 6 – lead acetate + L-arginine. The research carried out the study state of the redox reactions, the content of nitric oxide (NOx) stable metabolites, a lipid profile, the level of NO-synthase (eNOS) expression in the vascular endothelium, the main processes of urination and the activity of Na+/K+-ATPase in the renal tissue layers, as well as in the liver. The results were subjected to statistical processing.Results. Saturnism caused the oxidative stress development, a decrease in the NOx content in blood plasma, a violation of the L-arginine for eNOS bioavailability, and an endothelial dysfunction. Indicators of the impaired renal function were a decrease in the glomerular filtration rate (GFR), the tubular reabsorption of water, sodium, and the Na+/K+-ATPase activity. The damage to hepatocytes was evidenced by changes in the activity of organ-specific enzymes in the blood and Na+/K+-ATPase. L-arginine exhibited antioxidant properties, increased the NOx content and the level of eNOS expression. The eNOS L-nitroarginine methyl ester inhibitor showed the effects opposite to L-arginine.Conclusion. Biochemical markers of damage to kidney and liver cells during saturnism are indicators of the oxidative stress, NOx deficiency and hemodynamic disturbances in them. These mechanisms involved the following pharmacological substances: an eNOS inhibitor, L-nitroarginine methyl ester, which caused a decrease in the expression level of the enzyme, and an eNOS inducer, L-arginine, which increased this indicator severity. The lead toxicity mechanisms have been implicated in the impaired cholesterol metabolism, contributing to the L-arginine reduced availability for eNOS and the NOx production. Therefore, the use of L-arginine can be recommended as a regulator of the oxidative stress and an NO-producing endothelial function in other pathologies.
Publisher
Volgograd State Medical University
Subject
Pharmacology (medical),Pharmaceutical Science,Pharmacology,Pharmacy,Pharmacology (nursing)