Amal Hofni, Fares E M Ali, Ahmed R N Ibrahim, Esam M Aboubaker
{"title":"百里醌对链脲佐菌素诱导的糖尿病肾病的肾保护作用:NOX2和Nrf2信号的作用","authors":"Amal Hofni, Fares E M Ali, Ahmed R N Ibrahim, Esam M Aboubaker","doi":"10.2174/1874467216666230125150112","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy.</p><p><strong>Methods: </strong>Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks.</p><p><strong>Results: </strong>STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities.</p><p><strong>Conclusion: </strong>The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.\",\"authors\":\"Amal Hofni, Fares E M Ali, Ahmed R N Ibrahim, Esam M Aboubaker\",\"doi\":\"10.2174/1874467216666230125150112\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy.</p><p><strong>Methods: </strong>Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks.</p><p><strong>Results: </strong>STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities.</p><p><strong>Conclusion: </strong>The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.</p>\",\"PeriodicalId\":10865,\"journal\":{\"name\":\"Current molecular pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current molecular pharmacology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.2174/1874467216666230125150112\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular pharmacology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/1874467216666230125150112","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.
Objective: Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy.
Methods: Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks.
Results: STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities.
Conclusion: The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.
期刊介绍：
Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology.
Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.
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