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

Abstract

Mitochondria sustain healthy brain function. Herein we aimed to evaluate the thiamethoxam (MX) effect on the rat brain mitochondria in addition to the protective role of N-acetylcysteine (NAC) against MX harmful effects. Thiamethoxam was administered orally with five doses each week for 28 days to male albino rats at 1/50 of the LD50 (31.26 mg/kg bw). The results demonstrated that the thiamethoxam neurotoxicity was confirmed by the significant rising in acetylcholinesterase, and lactate dehydrogenase activities of plasma. A significant increase in mitochondrial antioxidants as superoxide dismutase and reduced glutathione was found. Also, significant induction of the oxidative stress and DNA damage via rising the malondialdehyde, and 8-hydroxy-2'-deoxyguanosine biomarkers was recorded by 32.5% and 118.61% respectively. Substantial depression in mitochondrial NADH dehydrogenase, cytochrome c reductase, cytochrome c oxidase, and Mg 2+ ATPase complexes as well as 23 % cerebral infarction was manifested by histological evaluation using the dehydrogenase activity indicator, 2, 3, 5-triphenyl tetrazolium chloride staining. In conclusion, MX can pose a hazard to the integrity and functioning of rats' brain mitochondria, perhaps leading to neurodegenerative disorders. Additionally, earlier treatment of the synthetic antioxidant N-acetylcysteine could prove beneficial in combating the harmful effects of thiamethoxam.

The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats

“…Based on our findings, it is reasonable to speculate that TMX (or its metabolites) functions as a nicotinic agonist, activating nAChRs and changing cholinergic transmission to restore normal activity (Khaldoun-Oularbi et al 2017 ). The current findings are consistent with those of Abdel-Razik et al ( 2022 ), who revealed a significant increase in plasma AchE as a result of TMX treatment. Monoamine concentrations were also observed to be significantly lower in thiacloprid-exposed embryos.…”

“…Oxidative stress caused by the overproduction of ROS and reactive nitrogen species, as well as changes in antioxidant enzyme activities, is implicated in NEO-induced injury to cellular molecules such as lipids, DNA, and proteins (Wang et al 2018 ; Abdel-Razik et al 2022 ). In the present study, brain oxidative damage was induced in TMX-exposed rats, as demonstrated by high levels of TBARS and significant inhibition of antioxidant enzymes.…”

“…Neurotransmission is disrupted by NEO insecticides; hence, the cholinergic neurotransmitter system is anticipated to be the most injured in mammals. This system is critical for cognitive function control, and its malfunction has been associated with the onset of a variety of neurodegenerative disorders (Hampel et al 2018 ; Abdel-Razik et al 2022 ). Based on our findings, it is reasonable to speculate that TMX (or its metabolites) functions as a nicotinic agonist, activating nAChRs and changing cholinergic transmission to restore normal activity (Khaldoun-Oularbi et al 2017 ).…”

The potential neuroprotective of luteolin against acetamiprid-induced neurotoxicity in the rat cerebral cortex

“…Also, they noted a rise in the enzyme activity of glutathione s-transferase and the rate of MDA. The structural and functional abnormalities in nerve tissue after exposure to neonicotinoid insecticides are attributed to the depletion and inactivation of thiol-containing proteins (51). Glutathione and its derived enzymes are the first lines of antioxidant defence against toxic agents-induced oxidative stress.…”