Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway

Abstract

Cypermethrin (CYP), a type II synthetic pyrethroid, is the most widely used insecticide worldwide. Inhalation of it may cause side effects. This study is aimed to examine potential protection of quercetin (QUE) which is a well-known antioxidant in CYPinduced lung toxicity. Accordingly, 35 Spraque Dawley male rats were divided into five equal groups as follows: I-Control group, II-QUE group (50 mg/kg/b.w. QUE), III-CYP group (25 mg/kg/b.w. CYP), IV-CYP + QUE 25 (25 mg/kg/b.w. CYP + 25 mg/ kg/b.w. QUE), V-CYP + QUE (25 mg/kg/b.w. CYP + 50 mg/kg/b.w. QUE) were treated with oral gavage throughout 28 days. CYP intoxication was associated with increased malondialdehyde level while glutathione concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase reduced. CYP adminisitration caused of apoptosis in the lung by up-regulating caspase-3 and Bax levels and down-regulating Bcl-2. CYP also caused of endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF6, and GRP78. Additionally, it was observed that CYP administration activated IL-6/JAK2/STAT3/MAPK14 signaling pathway and levels of IL-1β, NF-κB, TNF-α, and iNOS in the lung tissue. Therefore, it was determined that CYP administration triggered autophagy by upregulating LC3A and LC3B mRNA transcript levels. Moreover, the protein levels of NF-κB, caspase-3, Bax, Bcl-2, and cytochorme-c were examined by Western blot analysis. However, cotreatment with QUE at a dose of 25 and 50 mg/kg considerably protective oxidative stress, inflammation, apoptosis, ER stress, autophagy, and IL-6/JAK2/STAT3/MAPK14 signaling pathway in lung tissue. Overall, the findings of this study suggest that lung damage associated with CYP toxicity could be protected by QUE administration.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats

“…Cyp metabolites may lead to hepatic cell damage, producing reactive oxygen species (ROS); thus, oxidative stress is caused [ 10 ]. Furthermore, oxidative stress leads to oxidative damage of lipid content, protein oxidation, and DNA damage [ 11 ], which further activate inflammation and apoptosis in the liver [ 12 ].…”

Identification and immunological characterization of endoplasmic reticulum stress-related molecular subtypes in bronchopulmonary dysplasia based on machine learning

“…The ER is Frontiers in Physiology frontiersin.org essential to the process of alveoli production in the following ways: 1) preserving the function of the mitochondria; 2) correction of growth factor and receptor post-translation modifications; 3) reducing oxidative stress production; and 4) control of inflammation (Chan et al, 2016;Biwer and Isakson, 2017;Koksal et al, 2021). It has been observed that HOX and interferon-gamma increase ER stress in the lungs of newborn mice, thus causing lung damage and the arrival of neutrophils (Ileriturk et al, 2022). Non-etheless, further research is necessary to confirm the exact mechanisms underpinning ER stress and its modulatory involvement in different disorders.…”

Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model

“…Oxidative stress causes NF‐κB activation which leads to increased expression of pro‐inflammatory cytokines, thus triggering the inflammatory process 30,39–41 . The interaction between ER stress and inflammation has been extensively studied in cell types with metabolic or immune functions, and inflammation has been associated with unfolded protein response (UPR) activation to promote disease development 38 .…”

“…Oxidative stress causes NF-κB activation which leads to increased expression of pro-inflammatory cytokines, thus triggering the inflammatory process. 30,[39][40][41] The interaction between ER stress and inflammation has been extensively studied in cell types with metabolic or immune functions, and inflammation has been associated with unfolded protein response (UPR) activation to promote disease development. 38 In many previous studies, it has been reported that organophosphate compounds, including MLT, trigger inflammation by increasing the expression of pro-inflammatory cytokines in various tissues.…”