Hassanen Eman I, Hassan Neven H, Hussien Ahmed M, Ibrahim Marwa A, Ali Merhan E
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza, Egypt.
Department of Physiology, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza, Egypt.
Toxicol Appl Pharmacol. 2025 Feb;495:117223. doi: 10.1016/j.taap.2024.117223. Epub 2024 Dec 30.
Methomyl (MET), a universally used insecticide, has many adverse effects on various organs in both humans and animals including the liver, kidneys, and heart. Betaine (BET), a natural antioxidant, has a protective role against many toxicants-induced cardiovascular disorders. The present study was designed to elucidate the molecular mechanistic way underlying the mitigating effect of BET against MET-induced cardiopulmonary injury and inflammation in rats. Four groups of rats were used and orally administered the consequent materials daily for 28 days: normal saline, BET (250 mg/kg bwt), MET (2 mg/kg bwt), MET + BET. Blood and tissue (heart & lungs) samples were collected to assess the oxidative stress markers, lipid profile, biochemical markers, microscopic appearance, and inflammatory gene regulations. The results proved that MET induced oxidant/antioxidant imbalance, elevation of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels, and deterioration in lipid profile. The histopathological inspection showed severe myocardial necrosis and interstitial pneumonia along with bronchitis and alveolar damage. There was a marked increase in the intensity of cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) immunostaining with marked upregulation of the transcriptase levels of keap-1gene and downregulation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) genes in both heart and lung tissues of MET group. Otherwise, the coadministration of BET with MET markedly alleviated the abovementioned toxicological parameters. We can conclude that BET was able to reduce the MET-induced oxidative stress-mediated cardiovascular injury and pulmonary inflammation by modulating Keap-1/Nrf-2 signaling pathway and inactivating Cox-2 and iNOS expression which therefore reduced further cellular damage and inflammatory response.
灭多威（MET）是一种广泛使用的杀虫剂，对人和动物的各种器官都有许多不良影响，包括肝脏、肾脏和心脏。甜菜碱（BET）是一种天然抗氧化剂，对许多毒物诱导的心血管疾病具有保护作用。本研究旨在阐明BET对MET诱导的大鼠心肺损伤和炎症的缓解作用的分子机制。将四组大鼠用于实验，每天口服相应物质，持续28天：生理盐水、BET（250毫克/千克体重）、MET（2毫克/千克体重）、MET + BET。采集血液和组织（心脏和肺）样本，以评估氧化应激标志物、血脂谱、生化标志物、微观外观和炎症基因调控。结果证明，MET诱导了氧化/抗氧化失衡、血清肌酸激酶（CK）和乳酸脱氢酶（LDH）水平升高以及血脂谱恶化。组织病理学检查显示严重的心肌坏死和间质性肺炎，伴有支气管炎和肺泡损伤。在MET组的心脏和肺组织中，环氧合酶-2（Cox-2）和诱导型一氧化氮合酶（iNOS）免疫染色强度显著增加，keap-1基因转录水平显著上调，核因子红细胞2相关因子-2（Nrf-2）和血红素加氧酶-1（HO-1）基因下调。否则，BET与MET联合给药显著减轻了上述毒理学参数。我们可以得出结论，BET能够通过调节Keap-1/Nrf-2信号通路以及使Cox-2和iNOS表达失活，从而减少MET诱导的氧化应激介导的心血管损伤和肺部炎症，进而减少进一步的细胞损伤和炎症反应。
