Chlorpyrifos acute exposure induces hyperglycemia and hyperlipidemia in rats
ABSTRACT In this study we evaluated the hyperglycemic and hyperlipidemic effects of chlorpyrifos (CPF) after an acute exposure in rats. The mechanisms involved in hyperglycemia induced by CPF were studied. A single dose of CPF (50 mg kg(-1), subcutaneous, s.c.) was administered to overnight-fasted rats. Glucose and corticosterone levels, lipid status and paraoxonase (PON1) activity were determined in plasma of rats. Cardiovascular risk factors and the atherogenic index were calculated. Glycogen levels, tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6Pase) activities were determined in livers of rats. Cerebral acetylcholinesterase (AChE) activity was also determined. CPF caused an increase in glucose and glycogen levels as well as in TAT and G6Pase activities. The CPF exposure caused an increase in corticosterone levels, an inhibition of AChE activity and a reduction of PON1 activity. Regarding the lipid status, CPF induced an increase in triglycerides (TG) and low-density lipoprotein-cholesterol (LDL) levels and a decrease in high-density lipoprotein (HDL) levels associated with an increase of cardiovascular risk factors and the atherogenic index. The present study demonstrated that a single CPF administration caused hyperglycemia and hyperlipidemia in rats. The activation of the gluconeogenesis pathway, probably elicited by hypercorticosteronemia, is involved in the hyperglycemic effect of CPF in rats.
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ABSTRACT: The present study evaluated the beneficial effect of acetyl-L-carnitine (ALC) on subacute chlorpyrifos (CPF)-induced alterations in serum lipid profiles and some biomarkers of oxidative stress in Wistar rats. Twenty-eight adult male rats divided into four groups of seven animals each (group I–IV) were used: I (S/oil) received soya oil (2 ml kg−1), II (ALC) received ALC (300 mg kg−1); III (CPF) received CPF (8.5 mg kg−1 ∼ 1/10th LD50); IV (ALC+CPF) was pretreated with ALC (300 mg kg−1) and then exposed to CPF (8.5 mg kg−1), 30 min later. The treatment was orally for 28 days duration. Sera obtained from blood samples were evaluated for the levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and catalase (CAT). The levels of low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c), and atherogenic index (AI) were calculated. The result showed that elevated levels of TG, TC, LDL-c, VLDL-c, AI, and MDA, and the decreased levels of HDL-c, CAT, and SOD induced by CPF were modulated by ALC. It was concluded that ALC ameliorated the alterations in serum lipid and oxidative stress induced by CPF exposure in the rats, partly through its antioxidant properties.Toxicological and Environmental Chemistry 03/2013; 95(3). DOI:10.1080/02772248.2013.782029 · 0.72 Impact Factor
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ABSTRACT: Organophosphorus pesticides are known to disturb glucose homeostasis and increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on insulin signaling pathways and the protective effects of N-acetylcysteine (NAC). Malathion (200mg/kg) and NAC (2g/l) were administered orally to rats, during 28 consecutive days. Malathion increases plasma glucose, plasma insulin and Glycated hemoglobin levels. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The GP, GSK3β and PEPCK mRNA expressions were amplified by malathion while, the expression of glucokinase gene is down-regulated. On the basis of biochemical and molecular findings, it is concluded that malathion impairs glucose homeostasis through insulin resistance and insulin signaling pathways disruptions in a way to result in a reduced function of insulin into hepatocytes. Otherwise, when malathion-treated rats were compared to NAC supplemented rats, fasting glucose and insulin levels, as well as insulin resistance indices were reduced. Furthermore, NAC restored liver GP and PEPCK expression. N-acetylcysteine showed therapeutic effects against malathion-induced insulin signaling pathways disruption in liver. These data support the concept that antioxidant therapies attenuate insulin resistance and ameliorate insulin sensitivity.General and Comparative Endocrinology 10/2014; 215. DOI:10.1016/j.ygcen.2014.10.002 · 2.67 Impact Factor
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ABSTRACT: Abstract Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.Drug and Chemical Toxicology 07/2014; DOI:10.3109/01480545.2014.933348 · 1.10 Impact Factor