Biochemical evidence on the potential role of organophosphates in hepatic glucose metabolism toward insulin resistance through inflammatory signaling and free radical pathways

Abstract

Several studies show that organophosphate pesticides exert several effects on glucose homeostasis. The current study investigates the influence of subchronic exposure to malathion (MT) on hepatic gluconeogenesis in relation to acetyl cholinesterase (AChE) inhibition, oxidative stress and inflammatory response in the rat. MT was administered by gavage at doses of 25, 50 and 100 mg/kg for 32 days. Fasting hyperglycemia was seen in line with an increased activity of hepatic phosphoenolpyruvate carboxykinase, glucose 6-phosphatase and tumor necrosis factor α. In addition to the impaired glucose tolerance and inhibition of AChE in a dose-dependent manner, there were significant increases in hepatic lipid peroxidation, carbonyl groups and 8-deoxyguanosine as the biomarkers of reactive oxygen species-mediated damage to lipid, protein and DNA, respectively. Altered quality of the liver in glucose production especially gluconeogenesis could be a compensatory mechanism against MT toxicity or even result in tissue damage. MT-induced insulin resistance in the liver occurs through oxidative and inflammatory signaling pathways.

Neurocognitive, Mental Health, and Glucose Disorders in Farmers Exposed to Organophosphorus Pesticides

“…It is estimated that the number of people who suffer from type 2 diabetes will rise from 171 million in 2000 to 366 million in 2030 (16). Many studies corroborate that OP exposure might contribute to type 2 diabetes (17)(18)(19)(20)(21)(22)(23)(24)(25). Although the overall evidence of neurological and neurobehavioral effects of long-term OP exposure is thought to be small, it is not that diffi cult to fi nd some (26,27).…”

Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine

“…There are many reports which suggest that OPs insecticides manifest their toxic effects via insulin resistance and type 2 diabetes Mostafalou et al, 2012). The present study provides that organophosphate exposure disrupts major control points for the insulin signaling pathway.…”

“…For instance, a study performed by Montgomery et al (2008) indicated extra incidence of diabetes among OPs applicators who worked between 1993 and 2003 in the US. Moreover, according to epidemiological reports (Rezg et al, 2010;Slotkin, 2011), clinical studies (Saldana et al, 2007;Raafat et al, 2012) and experimental data Mostafalou et al, 2012) OPs increase the risk of insulin resistance and type 2 diabetes induction.…”

“…The longterm health effects after an acute or chronic exposure to OPs have been extensively studied (Moretto and Colosio, 2011;Starks et al, 2012;Grandjean and Landrigan, 2014). Metabolic disorders (Lasram et al, 2009), oxidative stress (Alp et al, 2011), immunotoxicity (Nain et al, 2011), inflammation (Mostafalou et al, 2012) and hepatotoxicity (Kalender et al, 2010) have also been reported. Furthermore, OPs are known to produce variety of biochemical and metabolic changes, some of which may be responsible for the adverse biological effects reported in man and animals such as type 2 diabetes.…”

Cytoprotective Effects of Melatonin Against Amitriptyline-Induced Toxicity in Isolated Rat Hepatocytes

“…7 It is assumed that the accumulation of the aren oxide metabolites could be the responsible mechanism for the cellular damage caused by this drug. [8][9][10] It was previously reported that amitriptyline induced oxidative stress, it increased ROS formation and lipid peroxidation also amitriptyline increased GSH consumption in isolated rat hepatocytes. 9 In addition, a previous study showed that amitriptyline caused mitochondrial membrane potential reduction.…”