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
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
Externí odkaz: