The ameliorative effect ofN‐acetylcysteine against penconazole induced neurodegenerative and neuroinflammatory disorders in rats

Abstract

Penconazole (PEN) is a widely used systemic fungicide to treat various fungal diseases in plants but it leaves residues in crops and food products causing serious environmental and health problems. N-acetylcysteine (NAC) is a precursor of the antioxidant glutathione in the body and exerts prominent antioxidant and antiinflammatory effects. The present study aimed to explore the mechanistic way of NAC to ameliorate the PEN neurotoxicity in male rats. Twenty-eight male rats were randomly divided into four groups (n = 7) and given the treated material via oral gavage for 10 days as the following: Group I (distilled water), Group II (50 mg/kg body weight [bwt] PEN), Group III (200 mg/kg bwt NAC), and Group IV (NAC + PEN).After 10 days all rats were subjected to behavioral assessment and then euthanized to collect brain tissues to perform oxidative stress, molecular studies, and pathological examination. Our results revealed that PEN exhibits neurobehavioral toxicity manifested by alteration in the forced swim test, elevated plus maze test, and Y-maze test. There were marked elevations in malondialdehyde levels with reduction in total antioxidant capacity levels, upregulation of messenger RNA levels of bax, caspase 3, and caspase 9 genes with downregulation of bcl2 genes. In addition, brain sections showed marked histopathological alteration in the cerebrum and cerebellum with strong bax and inducible nitric oxide synthetase protein expression. On the contrary, cotreatment of rats with NAC had the ability to improve all the abovementioned neurotoxic parameters. The present study can conclude that NAC has a neuroprotective effect against PEN-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic effect. We recommend using NAC as a preventive and therapeutic agent for a wide variety of neurodegenerative and neuroinflammatory disorders.

Comparative assessment on the probable mechanisms underlying the hepatorenal toxicity of commercial imidacloprid and hexaflumuron formulations in rats

“…The results of oxidative stress evaluations reflected on the histopathological picture of liver and kidneys of rats receiving IM and HFM that showing severe pathological alterations related to ROS overproduction. Several studies reported that ROS overproduction increasing cell and mitochondrial membrane permeability and prompts mitochondrial dysfunction disrupting Na/K/ATPase pump causing ionic imbalance (Khalaf et al 2020;Morgan et al 2021) This mechanism explained the observed hepatocellular and renal tubular epithelial cells degeneration in the present Values with different letters are significantly different at P ≤ 0.05 study. Furthermore, oxidative stress causing mitochondrial dysfunction and opining mitochondrial transition pores that increase the cytosolic Ca levels which activate several enzymes leading to protein degradation, lipid peroxidation and DNA damage (Mansour and Mossa 2010).…”

Ameliorative effect of N‐acetylcysteine on the testicular tissue of adult male albino rats after glyphosate‐based herbicide exposure

“…Moreover, several studies have reported the protective effect of NAC on oxidative stress and apoptosis against various toxins. [58][59][60][61][62][63] NAC can compensate for the adverse effects induced by GLP through its antioxidant and antiapoptotic effects. The antioxidant effect of NAC is attributed to increased levels of glutathione, [23] while the antiapoptotic and cytoprotective impact of NAC is associated with its ability to regulate some apoptosis-and inflammation-related genes.…”

The sesquiterpenoid valerenic acid protects neuronal cells from the detrimental effects of the fungicide benomyl on apoptosis and DNA oxidation

“…[67][68][69] Indeed, ginseng aqueous extract ameliorates hepatorenal toxicity caused by an insecticide in rats. 70 Moreover, N-acetylcysteine, a precursor molecule of reduced GSH, the most important endogenous antioxidant molecule, acts protectively against penconazole-induced neurodegenerative and neuroinflammatory disorders in rats, 71 lupeol protects against mancozeb-induced genotoxicity in human lymphocytes 72 and ascorbic acid supplementation is effective against cytotoxicity and DNA fragmentation induced by triphenyltin on human liver carcinoma cells. 73 In addition, manganese supresses oxidative stress, inflammation and caspase-3 activation in rats exposed to chlorpyrifos 74 and VA protects against benomylinduced oxidative stress and apoptosis in neural cells.…”