Mechanism of acute endosulfan intoxication-induced neurotoxicity in Sprague-Dawley rats / Mehanizam akutne neurotoksičnosti u Sprague-Dawley štakora izazvane trovanjem endosulfanom

Abstract

The purpose of this study was to investigate the molecular mechanism underlying oxidative and inflammatory neuronal cell death induced by endosulfan, a pesticide belonging to the chemical family of organochlorines. The cortical and hippocampal tissues derived from Sprague-Dawley (SD) rats treated with endosulfan exhibited increased intracellular accumulation of reactive oxygen species and oxidative damages to cellular macromolecules such as depletion of glutathione, lipid peroxidation, and protein carbonylation. Conversely, the expression of antioxidant enzymes including γ-glutamylcysteine ligase (GCL), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) was markedly reduced in the brain tissues exposed to endosulfan. Moreover, during endosulfan-induced neuronal cell death, mRNA expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was elevated, which seemed to be mediated by the activation of nuclear factor-kappa B (NF-κB) by phosphorylation of p65 subunit. These results suggest a new molecular mechanism underlying the endosulfan-induced acute neurotoxicity via induction of oxidative stress and pro-inflammatory responses.

A Narrative Review of Contemporary Lethal Pesticides: Unveiling the Ongoing Threat of Pesticide Poisoning

“…GABA is an inhibitory neurotransmitter that helps regulate nerve activity (108,109). Endosulfan inhibits GABA receptors, leading to overstimulation of nerve cells and various physiological effects (108,109).…”

Investigating cell type specific mechanisms contributing to acute oral toxicity_suppl1

“…Investigating Cell Type Specific Mechanisms Contributing to Acute Oral Toxicity approaches for chemical hazard or risk characterization that rely on an integrated analysis of existing information in a WoE assessment coupled with the generation of new information, if required (OECD, 2016a). An iterative approach that preferably relies on mechanistic information or available AOPs is followed to answer a defined question in a specific regulatory context, taking into account the acceptable level of uncertainty associated with the decision making (OECD, 2016a;Sachana and Leinala, 2017). The importance of understanding the mechanisms of acute toxicity was further recognized during an international workshop in which a group of experts discussed alternative approaches for identifying acute systemic toxicity (Hamm et al, 2017;Clippinger et al, 2018a).…”

Endosulfan removal through bioremediation, photocatalytic degradation, adsorption and membrane separation processes: A review

“…Moreover, endosulfan has a long half-life [33]. Hence, being persistent [34] and highly soluble in lipids [35,36], endosulfan accumulates in the food chain, hence posing a significant risk of exposure to humans [37].…”