Assessment of the Development of Metabolic Disorders Following Chronic Low-Dose Exposure to the Amine Salt of 2,4-Dichlorophenoxyacetic Acid in the Animal Experiment

Abstract

Introduction: 2,4-Dichlorophenoxyacetic acid (2,4-DA) is one of the most common environmental pollutants from the group of organochlorine herbicides. In our experiment, we focused on effects of low doses of 2,4-dichlorophenoxyacetic acid on metabolic parameters, which have been studied to a lesser extent. Objective: To assess the development of metabolic disorders following chronic low-dose exposure to the amine salt of 2,4-dichlorophenoxyacetic acid in an experiment. Materials and methods: The study was conducted on 36 male Wistar rats for 16 weeks in the spring-summer period with the 12/12 hour day/night cycle. Only healthy animals with the body weight of 170±3 g were included in the experiment and divided into the control and exposure groups (Groups 1 and 2, respectively) of 18 animals each. The latter were exposed to 0.5 MAC of 2,4-DA administered with drinking water (0.3–0.4 µg/kg/day). At week 14, the animals underwent a glucose tolerance test. To assess the development of metabolic disorders, the following parameters were measured in blood serum: total protein, albumin, creatinine, uric acid, activity of aspartate and alanine transaminases, alkaline phosphatase, lactate dehydrogenase, total cholesterol, high-density lipoprotein cholesterol, very low- and low-density lipoprotein cholesterol, and triacylglycerols. Statistica 10.0 was used for the analysis. The data were normally distributed (chi-squared test) and are presented as mean (M) and standard error of the mean (m). Results: We observed a decrease in the levels of total protein and albumin and a moderate increase in the activity of serum enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase) accompanied by the development of hypercholesterolemia, triacylglyceridemia, and dyslipoproteinemia. Results of the glucose tolerance test showed that low doses of 2,4-dichlorophenoxyacetic acid induced insulin resistance in the exposed animals. The main parameters of chemiluminescence in their blood serum, such as spontaneous luminescence, fast flash amplitude, and light sum, were 2.4, 9.3, and 4.1 times higher than in the controls, respectively. We also established a decrease in the level of serum iron by 20 % and an increase in that of ferritin by 12 % compared to the control rats. Conclusions: Long-term low-dose exposure to 2,4-DA induced an increase in the level of markers of metabolic disorders, which can be used to diagnose and assess the state of metabolic processes in the body.