Chlorpyrifos acute exposure induces hyperglycemia and hyperlipidemia in rats

Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Chemosphere (Impact Factor: 3.34). 07/2012; 89(5):602-8. DOI: 10.1016/j.chemosphere.2012.05.059
Source: PubMed


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.

5 Reads
  • Source
    • "In the current investigation, repeated exposure to CPF induced moderate fasting hyperglycemia 8 weeks after the treatment started. In this context, only two studies have explored the role of CPF in disturbing glucose homeostasis throughout adulthood (Acker and Nogueira, 2012; Elsharkawy et al., 2013). Despite differences in experimental protocols, our data are in agreement with those reported by these studies, which found an increase in glucose levels in both Wistar and Sprague-Dawley adult male rats after a single acute dose of 50 mg/kg CPF (Acker and Nogueira, 2012) and following a 3 month-period of oral exposure to CPF at 30 mg/kg body weight (Elsharkawy et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Our recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Thus, we aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. We examined body weight status, food and water intake, lipid and glucose homeostasis, metabolic biomarkers concentrations, insulin levels and insulin resistance, and leptin and ghrelin profiles. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health. Copyright © 2015 Elsevier Inc. All rights reserved.
    Environmental Research 07/2015; 142:169-76. DOI:10.1016/j.envres.2015.06.036 · 4.37 Impact Factor
  • Source
    • "This antiathrogenicity comes from the ability to protect lipoprotein particles from free radical oxidation because it can hydrolyze oxidized cholesterol esters , phospatidylcholine core aldehyde , and degrade hydrogen peroxides ( Aviram and Rosenblat 2004 ) . The beneficial effect of this enzyme on atherosclerosis has been supported by several studies directly or indirectly showing that PON1 reduces oxi - dative stress ( Gabrowny , Farag , and Sallam 2007 ; Acker and Nogueira 2012 ) . This has also been supported by this study indirectly through its effect on HDL - c and LDL - c though it was not assayed in this study . "
    [Show abstract] [Hide abstract]
    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 · 0.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study assessed whether exposure to pesticides elicits early biochemical changes in biomarkers of liver function and looked for potential gene-environmental interactions between pesticide exposure and polymorphisms of pesticide-metabolizing genes. A longitudinal study was conducted in farm-workers from Andalusia (South Spain), during two periods of the same crop season with different degree of pesticide exposure. Blood samples were taken for the measurement of serum and erythrocyte cholinesterase activities as well as for determining clinical chemistry parameters as biomarkers of liver function. Serum lipid levels were also measured as they may help to monitor the progress of toxic liver damage. A reduction in serum cholinesterase was associated with decreased levels of all clinical chemistry parameters studied except HDL-cholesterol. Conversely, a decreased erythrocyte cholinesterase (indicating long-term pesticide exposure) was associated with increased levels of aspartate aminotransferase and alkaline phosphatase and increased levels of triglycerides, total cholesterol and LDL-cholesterol, but reduced levels of HDL-cholesterol. Changes in liver biomarkers were particularly associated with the PON155M/192R haplotype. The obtained results therefore support the hypothesis that pesticide exposure results in subtle biochemical liver toxicity and highlight the role of genetic polymorphisms in pesticide-metabolizing enzymes as biomarkers of susceptibility for developing adverse health effects.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013; 61. DOI:10.1016/j.fct.2013.05.012 · 2.90 Impact Factor
Show more