Imidacloprid affects rat liver mitochondrial bioenergetics by inhibiting F_oF₁-ATP synthase activity

Abstract

Imidacloprid (IMD) is a neonicotinoid insecticide widely used in crops, pets, and on farm animals for pest control. Several studies were conducted examining the adverse effects of IMD on animals often exhibiting hepatic damage. The aim of this study was to determine the effects of IMD on bioenergetics of mitochondria isolated from rat liver. Imidacloprid (50-200 µM) produced a concentration-dependent decrease in oxygen consumption and ATP production without markedly affecting mitochondrial membrane potential (MMP). Oxygen consumption experiments showed that IMD did not significantly affect the respiratory chain, and this was similar to findings with oligomycin and carboxyatractyloside, suggesting a direct action on FF-ATP synthase and/or the adenine nucleotide translocator (ANT). Imidacloprid inhibited FF-ATP synthase activity only in disrupted mitochondria and induced a partial inhibition of ADP-stimulated depolarization of the MMP. Our results indicate that IMD interacts specifically with FF-ATP synthase resulting in functional inhibition of the enzyme with consequent impairment of mitochondrial bioenergetics. These effects of IMD on mitochondrial bioenergetics may be related to adverse effects of this insecticide on the liver.

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

“…Organophosphate insecticides inhibit mitochondrial complex I in birds [393], and effects on complex IV and/or V have been reported in mammalian models [394,395]. Complex V is also inhibited by imidacloprid, abamectin, and DDE [392,396,397].…”

Deterioration of Cytochrome C Content and Mitochondrial Dysfunction in Brain of Male Rats after Sub-Chronic Exposure to Thiamethoxam and Protective Role of N- Acetylcysteine

“…Imidacloprid interacts exclusively with FoF1-ATP synthase, resulting in functional inhibition of the enzyme and impaired the mitochondrial bioenergetics (Bizerra et al, 2018). In addition, chlorpyrifos, cypermethrin, and imidacloprid induced hepatomitochondrial dysfunction in male albino rats as a result of the treatments by the 1/50 of the LD50 of each insecticide (Taha et al, 2021).…”

MtDNA Copy Number in Oral Epithelial Cells Serves as a Potential Biomarker of Mitochondrial Damage by Neonicotinoid Exposure: A Cross-Sectional Study

“…Mitochondria are an essential target of neonicotinoids not only for insects but also for mammals and humans . Despite the evidence that neonicotinoids may impair the mitochondrial bioenergetics and dysfunction in rats and mice, , the experimental data related to their adverse effects measured by human mtDNAcn remain scarce. Further study of the mechanisms underlying mitochondrial dysfunction at the molecular level is also needed to construct a complete analysis of the association between neonicotinoid exposure and mitochondrial damage in populations.…”