Abstract

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1β, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment.

Highlights

  • The potential risks of exposure to different pesticides have been the subject of multiple investigations

  • Lipoperoxidation and carbonylation were evaluated in the different brain areas of sham, vehicle and treated (150 or 300 mg/kg body weight permethrin) rats, after 15 days of treatment

  • Our results suggest that sub-chronic PERM exposure at sublethal doses induces oxidative stress in the rat brain even when using 1/10 and 1/30 of the reported LD50

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Summary

Introduction

The potential risks of exposure to different pesticides have been the subject of multiple investigations Different studies reported their effects on physiology, which can lead to the development of chronic degenerative diseases with epidemiological impact [1,2,3]. The residues of these compounds have been reported in food, water, sea life, birds, and biological substrates such as different tissues and breast milk [4,5,6,7,8]. Pyrethroids include 42 compounds divided into two types and originally were considered safe for humans and other animals [9] These compounds have become first-line insecticides for the control of domestic pests. Due to the constant use of pyrethroids in agricultural activities and in homes, they constitute a danger due to their accumulation in solid food [13]

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