Sublethal exposures of diazinon alters glucose homostasis in Wistar rats: Biochemical and molecular evidences of oxidative stress in adipose tissues

Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Iran
Pesticide Biochemistry and Physiology (Impact Factor: 2.01). 11/2013; 105(1):57–61. DOI: 10.1016/j.pestbp.2012.11.008


Disorder of glucose homeostasis is one of the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of adipose tissue in regulating blood glucose and the role of oxidative stress in toxicity of OPs and in the continue of our previous works, in the present study we focused on tumor necrosis factor alpha (TNFα), glucose transporter type 4 (GLUT4), and nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB) in a sublethal model of toxicity by diazinon as a common OPs.Following time-course study of various doses of diazinon in impairing blood glucose, dose of 70 mg/kg/day was found the optimum. Animals were treated for 4 weeks and after gavage of glucose (2 g/kg), the glucose change was evaluated at time-points of 0, 30, 60, 120 and 180 min to identify oral glucose tolerance test (GTT). In addition, serum insulin was measured in fasting condition. In adipose tissue, oxidative stress markers including reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and TNFα were evaluated. The mRNA expression of GLUT4, Nf-κB and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were also determined by real time reverse transcription polymerase chain reaction (RT-PCR). Diazinon at dose of 70 mg/kg/day impaired GTT and diminished insulin level while augmented ROS, NADPH oxidase, and TNFα. The GLUT4 mRNA expression was amplified by diazinon while unlikely, the expression of Nf-κB gene did not change.On the basis of biochemical and molecular findings, it is concluded that diazinon impairs glucose homeostasis through oxidative stress and related proinflammatory markers in a way to result in a reduced function of insulin inside adipose tissue. Although, diazinon interfered with pancreatic influence on the adipose tissue most probably via stimulation of muscarinic receptors, current data are not sufficient to introduce adipose tissue as a target organ to OPs toxicity. Considering the potential of OPs to accumulate in adipose tissue, it seems a good candidate organ for future studies. Although, hyperglycemia was not induced by diazinon but increased AUC0–180 min leads us to the point that diazinon induces kind of instability in glucose homostasis and diabetes.

Download full-text


Available from: Mohammad Abdollahi,
    • "Nevertheless, other studies have found increased levels of these parameters, particularly in populations exposed to OPs [29]. Disrupting effects of pesticides, in particular OPs, on glucose homeostasis have been reportedly linked to oxidative damages and inflammatory cytokines and are thought to be compensatory responses accompanied with reduced insulin signaling in insulin sensitive organs such as liver, muscle, and adipose tissue [29] [34] [39] [49]. Experimental studies have shown that a mixture of conazol and phenoxy acid herbicides induces decreases in cholesterol and AChE as a result of oxidative stress [1]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims: Although epidemiological studies have investigated associations between occupational pesticide exposures and different adverse health outcomes, they have rarely assessed individuals at two time-points of a same crop season with different pesticide use. Material and methods: Clinical symptoms, physical examination signs, hematological and clinical chemistry parameters were measured in 189 intensive agriculture workers and 91 healthy control subjects from Almeria coastline (Southeastern Spain) to evaluate potential effects of pesticide exposure. Key findings: Greenhouse workers showed an increased risk of ocular and skin signs relative to controls at the period of high pesticide exposure (OR: 4.80 and 2.87, respectively); however, no differences were observed for clinical symptoms. A greater risk for ECG changes (OR: 3.35) and altered spirometry (OR: 5.02) was found at the period of low exposure. Erythrocyte acetylcholinesterase was significantly decreased in greenhouse workers relative to controls in both periods. Assessment of hematological parameters revealed increased counts of erythrocytes, leukocytes, platelets and hemoglobin in greenhouse workers relative to controls, and also in the period of high versus low pesticide exposure. Changes in clinical chemistry parameters included decreased levels of glucose, creatinine, total cholesterol, triglyceride and alkaline phosphatase in greenhouse workers relative to controls; however, these parameters were raised in the period of high versus low pesticide exposure. Significance: These findings suggest that chronic occupational exposure to pesticides of lower toxicity than former compounds under integrated production systems elicit mild toxic effects, particularly targeting the skin and eyes, as well as subtle subclinical (biochemical) changes of unknown long-term consequences.
    Life sciences 10/2015; DOI:10.1016/j.lfs.2015.10.013 · 2.70 Impact Factor
  • Source
    • "The rate of oxidation from DCFH to dichlorofluorescein (DCF) indicative of oxidant production was followed at the excitation wavelength of 488 nm and emission wavelength of 525 nm and measured every 6 min for 60 min using an ELISA F-2000 fluorescence spectrometer. The rate was linear for at least 60 min at various concentrations of protein present, corrected for the autooxidation rate of DCFH [20] "
    [Show abstract] [Hide abstract]
    ABSTRACT: There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF- α ) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO.
    Oxidative Medicine and Cellular Longevity 02/2014; 2014:948951. DOI:10.1155/2014/948951 · 3.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: About 25 million agricultural workers in the developing world suffer from at least one episode of poisoning each year, mainly by anticholinesterase-like organophosphates (OPs). The objective of this cross-sectional study was to establish the OP toxicity in 187 occupationally exposed farmers in terms of neurocognitive impairment, mental health status, clinical symptoms, diabetes, and haematological factors. The exposed group was compared to 187 healthy age-, sex-, and education-matching controls. Neurocognitive impairment was measured using the Subjective Neurocognition Inventory (SNI) and mental health status using the General Health Questionnaire-28 (GHQ-28). The subjects were also tested for fasting blood glucose (FBG), blood urea nitrogen (BUN), cholesterol (CL), triglycerides (TG), creatinine, oral glucose tolerance test (GTT), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The exposed farmers showed higher FBG (p<0.001), BUN (p=0.007), CL (p<0.001), oral GTT (p<0.001), and lower AST (p<0.001), ALP (p<0.001), and creatinine (p=0.004) than controls. The rates of anxiety/ insomnia and severe depression were also significantly higher in the farmers than in controls (p=0.015 and p<0.001, respectively). Meanwhile, the rate of social dysfunction was significantly lower than in controls (p<0.001). Disorders affecting psychomotor speed, selective attention, divided attention, verbal memory, nonverbal memory, prospective memory, spatial functioning, and initiative/energy were all lower in the farmers (p<0.001). Farmers showed clinical symptoms eczema, saliva secretion, fatigue, headache, sweating, abdominal pain, nausea, superior distal muscle weakness, inferior distal muscle weakness, inferior proximal muscle weakness, breath muscle weakness, hand tingling, foot tingling, epiphoria, polyuria, miosis, dyspnoea, bradycardia, and rhinorrhoea, which all significantly correlated with the number of working years. These findings indicate that farmers who work with OPs are prone to neuropsychological disorders and diabetes.
    Archives of Industrial Hygiene and Toxicology 03/2013; 64(1):1-8. DOI:10.2478/10004-1254-64-2013-2296 · 0.93 Impact Factor
Show more