Abstract
Like other persistent organochlorine pesticides, endosulfan residues have been detected in foods including fruit, vegetables, and fish. The aim of our study was to assess the impact of a dietary exposure to low doses of endosulfan from foetal development until adult age on metabolic homeostasis in mice and to identify biomarkers of exposure using an 1H-NMR-based metabonomic approach in various tissues and biofluids. We report in both genders an increase in plasma glucose as well as changes in levels of factors involved in the regulation of liver oxidative stress, confirming the prooxidant activities of this compound. Some metabolic changes were distinct in males and females. For example in plasma, a decrease in lipid LDL and choline content was only observed in female. Lactate levels in males were significantly increased. In conclusion, our results show that metabolic changes in liver could be linked to the onset of pathologies like diabetes and insulin resistance. Moreover from our results it appears that the NMR-based metabonomic approach could be useful for the characterization in plasma of a dietary exposure to low dose of pesticide in human.
Highlights
Many epidemiological studies have shown that exposure to pesticides is a risk factor for human health, as evidenced by the positive correlation between professional exposure to these compounds and an increase in the incidence of various human diseases. e general population is exposed to pesticides mainly via food intake. us many people have a lifelong exposure to low doses of pesticides, the impact of which on human health is not yet known
Choline is a precursor for the synthesis of acetylcholine whose synthesis depends on the capture of choline in the blood. e level of circulating choline could have an impact at the neuronal level by accelerating neuronal transmission. is could be compared with the neurotoxicity of endosulfan which has been described elsewhere [43]. These results suggest that dietary exposure to endosulfan even at low doses could interfere with a number of physiological processes that regulate cell division, lipid metabolism, and neuronal transmission
Our metabonomic approach has enabled the detection of metabolic disturbances following dietary exposure to a low dose of endosulfan
Summary
Many epidemiological studies have shown that exposure to pesticides is a risk factor for human health, as evidenced by the positive correlation between professional exposure to these compounds and an increase in the incidence of various human diseases (reviewed in Merhi et al [1]). e general population is exposed to pesticides mainly via food intake. us many people have a lifelong exposure to low doses of pesticides, the impact of which on human health is not yet known.Organochlorine (OC) pesticides are among the most frequent contaminants found in the environmental compartments because they persist in the environment and bioaccumulate in organisms, partly due to their lipophilic properties [2]. Endosulfan has been shown to be toxic to the liver, kidney, nervous system, and reproductive organs of laboratory animals [8,9,10]. Exposure to this compound can modify the activity of some enzymes involved in oxidative stress and xenobiotic metabolism, as well as testosterone metabolism and clearance [11]. Whilst the toxicological effects of endosulfan have been studied in vitro and in vivo, the impact of long-term exposure to low doses through dietary intake in animal models from the foetal stage to adulthood has not yet been reported
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