Article

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

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.

0 Followers
 · 
7 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.
    Full-text · Article · Jul 2015 · Environmental Research
  • 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.
    Full-text · Article · Mar 2013 · Toxicological and Environmental Chemistry
  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is a progressive disabling neurodegenerative disorder characterized by severe difficulties with body motions and associated with autonomic dysfunction, depression, and dementia. Oxidative stress is thought to play an important role in the pathogenesis of PD and oxidative damage characterizes proteins, lipids, and DNA in the substantia nigra pars compacta (SNc) of PD patients. To date, L-dopa is the most effective medication for controlling PD symptoms, although long-term treatment can enhance oxidative stress and accelerate the degenerative process of residual cells. Thus, the inhibition of oxidation of L-dopa and the inhibition of reactive oxygen species formation are important strategies for neuro-protective therapy. Therefore, efforts are made not only to improve the effect of L-dopa treatment for PD, but also to investigate new drugs with both antioxidant and neuroprotective effects. Hespiridin (HDN), a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects including antioxidant, anti-hypercholesterolemic, antihyperglycemic, anti-inflammatory, anti-carcinogenic and neuro-protective actions. Chlorpyrifos (CPF) was used in this study as an animal model of PD. Model of CPF-induced Parkinsonism in rats produced neurotoxicity, oxidative stress, hyper-lipidemia, hyperglycemia and DNA damage. Seventy male rats were used in this study and divided into seven equal groups. After 6 weeks, the following groups were studied, control group, CPF group, HDN group, Sinemet group, CPF+HDN group, CPF+Sinemet group, and CPF+HDN+Sinemet group. Here in the present study, the treatment of parkinsonism with HDN alone or combined with sinemet provided a neuroprotection effect when given early in the course of the disease. In conclusion, HDN could be recommended as a disease-modifying therapy when given alone or mixed with L-dopa in course of Parkinson's disease.
    No preview · Article · Dec 2012 · Life Science Journal
Show more