Trigger Mechanisms of Cypermethrin-Induced Changes of Metabolism: An Experimental Study

Abstract

Background: The purpose of this work was to study the triggering mechanisms of metabolic changes in experimental animals after a single injection of cypermethrin at a dose of 55 mg/kg of body weight. Methods and Results: Sixty rats were randomly divided into four groups (15 rats in each group). Rats of the control groups (G1 and G3) were injected with saline into the stomach. Animals of the experimental groups (G2 and G4) were injected once with the synthetic pyrethroid cypermethrin at a dose of 55 mg/kg of body weight, which is 1/5 LD50. Before being withdrawn from the experiment, blood was taken in vivo under anesthesia, and the liver was removed. The glucose, lactate, uric acid, and total bilirubin concentrations were determined in blood serum by unified research methods. The content of glutathione (GSH), malondialdehyde (MDA), and activity of glucose-6-phosphate dehydrogenase (G6PDH) was determined in erythrocyte hemolysates. In liver homogenates, the content of total protein, glycogen, uric acid, and inorganic phosphorus (Pi) was determined by unified methods, as well as MDA, GSH, activity of G6PDH, microsomal oxygenase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR). Administration of cypermethrin to laboratory rats at a dose of 1/5 LD50 causes adaptive changes in metabolism. After one day, there was an increase in the content of glucose in the blood serum against the background of a deficiency of carbohydrates in the liver tissue. At the same time, there was an increase in anaerobic oxidation and an increase in purine catabolism, which was associated with the activation of lipid peroxidation (LP) of cell membranes and the depletion of the pool of antioxidants. GSH deficiency was exacerbated by an increase in the activity of antioxidant enzymes and xenobiotic biotransformation systems. Seven days after the administration of cypermethrin, rats retained a high rate of breakdown of purines to uric acid. This process was enhanced by a decrease in the RBC, a deficiency of carbohydrates, and inhibition of the activity of G6PDH, GPx, and GR. This ultimately led to the development of oxidative stress. Conclusion: The triggers for the development of oxidative stress under cypermethrin exposure are lactic acidosis and increased catabolism of purine mononucleotides, accompanied by an increase in the production of free radicals and inhibition of the function of the antioxidant system. A decrease in the blood RBC, carbohydrate deficiency, and suppression of the activity of the pentose cycle 7 days after the administration of cypermethrin aggravate this condition.