Tropisetron protects against brain aging via attenuating oxidative stress, apoptosis and inflammation: The role of SIRT1 signaling
Autor: | Hamidreza Mohammadi, Atefeh Mirshafa, Fereshteh Talebpour Amiri, Fatemeh Shaki, Mohammad Shokrzadeh, Ebrahim Mohammadi |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Aging Apoptosis Pharmacology medicine.disease_cause 030226 pharmacology & pharmacy Antioxidants Mice 0302 clinical medicine Sirtuin 1 Serotonin 5-HT3 Receptor Antagonists General Pharmacology Toxicology and Pharmaceutics bcl-2-Associated X Protein Neurons biology Chemistry Brain General Medicine Mitochondria Proto-Oncogene Proteins c-bcl-2 Tumor necrosis factor alpha medicine.symptom Injections Intraperitoneal medicine.drug Senescence Injections Subcutaneous Tropisetron Inflammation Nitric Oxide General Biochemistry Genetics and Molecular Biology Drug Administration Schedule 03 medical and health sciences medicine Animals Interleukin-6 Tumor Necrosis Factor-alpha Neurotoxicity Galactose medicine.disease Oxidative Stress 030104 developmental biology Gene Expression Regulation biology.protein Reactive Oxygen Species Oxidative stress |
Zdroj: | Life sciences. 248 |
ISSN: | 1879-0631 |
Popis: | Aims The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of tropisetron and to clarify whether it affects mitochondrial oxidative stress, apoptosis and inflammation in the aging mouse brain by upregulating Sirtuin 1 or silent information regulator 1 (SIRT1). Materials and methods Aging was induced by d -galactose (DG) at the dose of 200 mg/kg body weight/day subcutaneously injected to male mice for six weeks. Tropisetron was simultaneously administered intraperitoneally once a day at three various doses (1, 3 and 5 mg/kg body weight). Oxidative stress and mitochondrial dysfunction markers were evaluated. Nitric oxide (NO) and pro-inflammatory cytokines levels including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were studied. Besides, the expressions of apoptosis-associated genes (Bax and Bcl-2) and the aging-related gene (SIRT1) were determined by the real time polymerase chain reaction (RT-PCR). In addition, histopathological alterations were assessed. Key findings Tropisetron reversed the induction of oxidative damage, mitochondrial dysfunction and overproduction of inflammatory mediators induced by DG in the brain tissue. In addition, tropisetron suppressed DG-induced apoptosis and found to significantly elevate SIRT1 gene expression. Besides, tropisetron could markedly alleviate DG-induced abnormal changes in the brain morphology. Significance Tropisetron exhibited anti-aging effects in the context of DG-induced senescence in mouse brain through various pathways. Our results suggest that tropisetron may attenuate DG-induced brain aging via SIRT1 signaling activation. |
Databáze: | OpenAIRE |
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