Eman I Hassanen, Neven H Hassan, Ahmed M Hussien, Marwa A Ibrahim, Merhan E Ali
{"title":"甜菜碱通过iNOS/Cox2和Nrf2/HO1/Keap1信号通路缓解甲多梅酰引发的氧化应激介导的大鼠心肺炎症。","authors":"Eman I Hassanen, Neven H Hassan, Ahmed M Hussien, Marwa A Ibrahim, Merhan E Ali","doi":"10.1016/j.taap.2024.117223","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117223"},"PeriodicalIF":3.3000,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Betaine alleviates methomyl-triggered oxidative stress-mediated cardiopulmonary inflammation in rats through iNOS/Cox2 and Nrf2/HO1/Keap1 signaling pathway.\",\"authors\":\"Eman I Hassanen, Neven H Hassan, Ahmed M Hussien, Marwa A Ibrahim, Merhan E Ali\",\"doi\":\"10.1016/j.taap.2024.117223\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":23174,\"journal\":{\"name\":\"Toxicology and applied pharmacology\",\"volume\":\" \",\"pages\":\"117223\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology and applied pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.taap.2024.117223\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.taap.2024.117223","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Betaine alleviates methomyl-triggered oxidative stress-mediated cardiopulmonary inflammation in rats through iNOS/Cox2 and Nrf2/HO1/Keap1 signaling pathway.
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.
期刊介绍：
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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