Alyaa R. Salama, Neveen R. Ashoura, Kariman A. Esmail, Hossam G. Tohamy, Mustafa Shukry, Badriyah S. Alotaibi, Asmaa A. Aboushouk
{"title":"Melissa officinalis通过AMPK/SIRT1和STAT3/Nrf2通路减轻双氯芬酸诱导的肝肾毒性","authors":"Alyaa R. Salama, Neveen R. Ashoura, Kariman A. Esmail, Hossam G. Tohamy, Mustafa Shukry, Badriyah S. Alotaibi, Asmaa A. Aboushouk","doi":"10.1002/jat.4799","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Purpose</h3>\n \n <p>This study aimed to assess whether <i>Melissa officinalis</i> (MO) or lemon balm could counteract the detrimental effects of diclofenac (DIC) on the liver and kidneys in male albino rats.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Forty adult male Wistar rats were randomly assigned to four groups (<i>n</i> = 10 per group): control, DIC (10 mg/kg intraperitoneally), DIC + MO (10 mg/kg DIC IP + 200 mg/kg lemon balm orally), and MO only (200 mg/kg orally) for 28 days. Biochemical, molecular, and histopathological evaluations were conducted to assess organ function and tissue integrity.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>DIC significantly impaired hepatic and renal function (<i>p</i> < 0.05), evidenced by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP). Oxidative stress increased, as shown by higher malondialdehyde levels and reduced antioxidants, including glutathione and catalase (CAT). Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were also elevated. Histopathological analysis indicated severe tissue damage and cell death in the liver and kidneys from DIC. However, adding MO alongside DIC mitigated these effects, improving both biochemical and histopathological parameters in the liver and kidneys. Gene expression analysis revealed upregulation of STAT3 and TNF-α and downregulation of AMP-activated protein kinase (<i>AMPK</i>), sirtuin 1 (<i>SIRT1</i>), and nuclear factor erythroid 2–related factor 2 (<i>Nrf2</i>). Coadministration of MO significantly reversed these alterations (<i>p</i> < 0.05), improved tissue architecture, and restored antioxidant and anti-inflammatory balance.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>MO provided substantial protection against oxidative damage and functional disturbances induced by DIC in liver and kidney tissues.</p>\n </section>\n </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 8","pages":"1649-1663"},"PeriodicalIF":2.8000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Melissa officinalis Attenuates Diclofenac-Induced Hepatorenal Toxicity via AMPK/SIRT1 and STAT3/Nrf2 Pathways\",\"authors\":\"Alyaa R. Salama, Neveen R. Ashoura, Kariman A. Esmail, Hossam G. Tohamy, Mustafa Shukry, Badriyah S. Alotaibi, Asmaa A. 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Gene expression analysis revealed upregulation of STAT3 and TNF-α and downregulation of AMP-activated protein kinase (<i>AMPK</i>), sirtuin 1 (<i>SIRT1</i>), and nuclear factor erythroid 2–related factor 2 (<i>Nrf2</i>). 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引用次数: 0
摘要
目的:探讨香蜂草(MO)或柠檬香蜂草是否能抵消双氯芬酸(DIC)对雄性白化大鼠肝脏和肾脏的不良影响。方法:将40只成年雄性Wistar大鼠随机分为4组(每组10只):对照组、DIC (10 mg/kg腹腔注射)、DIC + MO (10 mg/kg DIC IP + 200 mg/kg柠檬香蜂草口服)、MO (200 mg/kg口服),持续28 d。通过生化、分子和组织病理学评估来评估器官功能和组织完整性。结果:DIC显著损害肝肾功能(p)。结论:MO对DIC引起的肝肾组织氧化损伤和功能障碍具有明显的保护作用。
Melissa officinalis Attenuates Diclofenac-Induced Hepatorenal Toxicity via AMPK/SIRT1 and STAT3/Nrf2 Pathways
Purpose
This study aimed to assess whether Melissa officinalis (MO) or lemon balm could counteract the detrimental effects of diclofenac (DIC) on the liver and kidneys in male albino rats.
Methods
Forty adult male Wistar rats were randomly assigned to four groups (n = 10 per group): control, DIC (10 mg/kg intraperitoneally), DIC + MO (10 mg/kg DIC IP + 200 mg/kg lemon balm orally), and MO only (200 mg/kg orally) for 28 days. Biochemical, molecular, and histopathological evaluations were conducted to assess organ function and tissue integrity.
Results
DIC significantly impaired hepatic and renal function (p < 0.05), evidenced by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP). Oxidative stress increased, as shown by higher malondialdehyde levels and reduced antioxidants, including glutathione and catalase (CAT). Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were also elevated. Histopathological analysis indicated severe tissue damage and cell death in the liver and kidneys from DIC. However, adding MO alongside DIC mitigated these effects, improving both biochemical and histopathological parameters in the liver and kidneys. Gene expression analysis revealed upregulation of STAT3 and TNF-α and downregulation of AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and nuclear factor erythroid 2–related factor 2 (Nrf2). Coadministration of MO significantly reversed these alterations (p < 0.05), improved tissue architecture, and restored antioxidant and anti-inflammatory balance.
Conclusion
MO provided substantial protection against oxidative damage and functional disturbances induced by DIC in liver and kidney tissues.
期刊介绍:
Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.