Faezeh Lorestani, Ahmad Movahedian, Adel Mohammadalipour, Mohammad Hashemnia, Mohammad Hossein Aarabi
{"title":"Astaxanthin prevents nephrotoxicity through <i>Nrf2/HO-1</i> pathway.","authors":"Faezeh Lorestani, Ahmad Movahedian, Adel Mohammadalipour, Mohammad Hashemnia, Mohammad Hossein Aarabi","doi":"10.1139/cjpp-2023-0015","DOIUrl":null,"url":null,"abstract":"<p><p>Renal toxicity is one of the side effects of methotrexate (MTX). Therefore, this study explored the use of astaxanthin (AST), as a natural carotenoid, against MTX-induced nephrotoxicity emphasizing the changes in oxidative stress and the expression of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (<i>Nrf2/HO-1</i>). During the 10 days of the experiment, male Wistar rats in different groups received MTX (10 mg/kg) on days 6, 8, and 10 and three doses of AST (25, 50, and 75 mg/kg) during the entire course. Renal failure caused by MTX was observed in significant histopathological changes and a significant increase in serum levels of creatinine, urea, and uric acid (<i>p</i> < 0.05). Oxidative change induced by MTX injection was also observed by remarkably increasing the tissue level of malondialdehyde (MDA) and decreasing the activity of superoxide dismutase (SOD) and catalase (<i>p</i> < 0.001). AST decreases the adverse effects of MTX by upregulating the expression of <i>Nrf2/HO-1</i> genes (<i>p</i> < 0.01) and decreasing the tissue level of MDA (<i>p</i> < 0.01). Also, AST significantly reduced the amount of creatinine, urea, and uric acid in the serum and improved the activity of SOD and catalase in the kidney tissue (<i>p</i> < 0.05). Thus, AST may protect the kidney against oxidative stress caused by MTX.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"128-136"},"PeriodicalIF":1.7000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Canadian journal of physiology and pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1139/cjpp-2023-0015","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/8 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Renal toxicity is one of the side effects of methotrexate (MTX). Therefore, this study explored the use of astaxanthin (AST), as a natural carotenoid, against MTX-induced nephrotoxicity emphasizing the changes in oxidative stress and the expression of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1). During the 10 days of the experiment, male Wistar rats in different groups received MTX (10 mg/kg) on days 6, 8, and 10 and three doses of AST (25, 50, and 75 mg/kg) during the entire course. Renal failure caused by MTX was observed in significant histopathological changes and a significant increase in serum levels of creatinine, urea, and uric acid (p < 0.05). Oxidative change induced by MTX injection was also observed by remarkably increasing the tissue level of malondialdehyde (MDA) and decreasing the activity of superoxide dismutase (SOD) and catalase (p < 0.001). AST decreases the adverse effects of MTX by upregulating the expression of Nrf2/HO-1 genes (p < 0.01) and decreasing the tissue level of MDA (p < 0.01). Also, AST significantly reduced the amount of creatinine, urea, and uric acid in the serum and improved the activity of SOD and catalase in the kidney tissue (p < 0.05). Thus, AST may protect the kidney against oxidative stress caused by MTX.
肾毒性是甲氨蝶呤(MTX)的副作用之一。因此,本研究探讨了虾青素(AST)作为一种天然类胡萝卜素的用途,以对抗MTX诱导的肾毒性,强调氧化应激的变化和核因子红系2相关因子2/血红素加氧酶1(Nrf2/HO-1)的表达。在实验的10天内,不同组的雄性Wistar大鼠在第6、8和10天接受MTX(10mg/kg),并在整个过程中接受三个剂量的AST(25、50和75mg/kg)。MTX引起的肾功能衰竭在显著的组织病理学变化中观察到,血清肌酐、尿素和尿酸水平显著升高(p p Nrf2/HO-1基因(p p
期刊介绍:
Published since 1929, the Canadian Journal of Physiology and Pharmacology is a monthly journal that reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership. The journal periodically publishes a “Made In Canada” special section that features invited review articles from internationally recognized scientists who have received some of their training in Canada.