Resveratrol Promotes Recovery of Hearing following Intense Noise Exposure by Enhancing Cochlear SIRT1 Activity

2017 ◽  
Vol 22 (4-5) ◽  
pp. 303-310 ◽  
Author(s):  
Hao Xiong ◽  
Yongkang Ou ◽  
Yaodong Xu ◽  
Qiuhong Huang ◽  
Jiaqi Pang ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Noise Exposure ◽  
Therapeutic Potential ◽  
High Dose ◽  
Protective Effects ◽  
Wide Range ◽  
Dependent Protein ◽  
Intense Noise ◽  
Protein Deacetylase

The sirtuin SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase known to have protective effects against a wide range of neurological disorders. In the present study, we discovered that C57BL/6 mice fed a long-term diet supplemented with high-dose resveratrol exhibited increased cochlear SIRT1 activity and presented a better recovery of hearing and less loss of hair cells after intense noise exposure compared with those fed a standard chew. Moreover, resveratrol attenuated cochlear SIRT1 decrease and reduced oxidative stress in the cochlea after noise exposure. These results suggest a considerable therapeutic potential of resveratrol for the treatment of noise-induced hearing loss.

scholarly journals Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis

2019 ◽  
Vol 20 (16) ◽  
pp. 4057 ◽  
Author(s):  
Yu Chiuan Wu ◽  
Han Hsiang Huang ◽  
Yi Jhen Wu ◽  
Ioannis Manousakas ◽  
Chin Chang Yang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Water Solubility ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Liver Injuries ◽  
Repeated Consumption ◽  
Histopathologic Findings ◽  
Poor Stability

Astaxanthin (Asta) has been demonstrated to possess anti-inflammatory, antitumor, and free radical-clearing activities. However, the poor stability and low water solubility of Asta hamper its bioavailability. The objectives of this study were to fabricate Asta-loaded liposomes (Asta-lipo) and investigate the therapeutic effects of Asta-lipo on alcoholic liver fibrosis in mice. The mice were administered with Asta-lipo or liposomes alone prior to a 3-week dose containing 30% alcohol with or without feeding with a second dose of 30% alcohol. The prepared Asta-lipo of 225.0 ± 58.3 nm in diameter, had an encapsulation efficiency of 98%. A slow release profile of 16.2% Asta from Asta-lipo was observed after a 24-h incubation. Restorative actions against alcoholic liver fibrosis were observed after oral administration of Asta-lipo for 4 weeks. Hepatic repair, followed by a second dose of 30% alcohol, suggested that Asta-lipo exerted protective and reparative effects against liver injuries induced by repeated consumption of alcohol. The changes of serum ALT and AST values were principally in consistence with the histopathologic findings. Asta-lipo exerted rapid and direct effects against repeated alcohol-induced liver disease, whereas Asta-lipo given orally could boost recovery from liver injuries obtained due to previous long-term alcohol use. These data demonstrate that Asta-lipo has applicable protective and therapeutic potential to treat alcohol-induced liver diseases.

scholarly journals An implant for long-term cervical vagus nerve stimulation in mice

2020 ◽  
Author(s):  
Ibrahim T. Mughrabi ◽  
Jordan Hickman ◽  
Naveen Jayaprakash ◽  
Eleni S. Papadoyannis ◽  
Adam Abbas ◽  
...  
Keyword(s):  
Heart Rate ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Therapeutic Potential ◽  
Therapeutic Implications ◽  
Wide Range ◽  
Heart Rate Threshold

AbstractVagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to treat a wide range of chronic conditions in which inflammation is implicated, including type 2 diabetes, obesity, atherosclerosis and heart failure. Many of these diseases have well-established mouse models but due to the significant surgical and engineering challenges that accompany a reliable interface for long-term VNS in mice, the therapeutic implications of this bioelectronic approach remain unexplored. Here, we describe a long-term VNS implant in mice, developed at 3 research laboratories and validated for between-lab reproducibility. Implant functionality was evaluated over 3-8 weeks in 81 anesthetized or conscious mice by determining the stimulus intensity required to elicit a change in heart rate (heart rate threshold, HRT). HRT was also used as a method to standardize stimulation dosing across animals. Overall, 60-90% of implants produced stimulus-evoked physiological responses for at least 4 weeks, with HRT values stabilizing after the second week of implantation. Furthermore, stimulation delivered through 6-week-old implants decreased TNF levels in a subset of mice with acute inflammation caused by endotoxemia. Histological examination of 4- to 6-week-old implants revealed fibrotic encapsulation and no gross fiber loss. This implantation and dosing approach provide a tool to systematically investigate the therapeutic potential of long-term VNS in chronic diseases modeled in the mouse, the most widely used vertebrate species in biomedical research.

scholarly journals Celastrol pretreatment as a therapeutic option against cisplatin-induced nephrotoxicity

2019 ◽  
Vol 8 (5) ◽  
pp. 723-730 ◽  
Author(s):  
Tugce Boran ◽  
Aysenur Gunaydin ◽  
Ayse Tarbin Jannuzzi ◽  
Eren Ozcagli ◽  
Buket Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Rat Kidney ◽  
Therapeutic Option ◽  
Control Group ◽  
Epithelial Cell Line ◽  
Protective Effects ◽  
Wide Range ◽  
Significant Difference

Abstract Celastrol is a natural bioactive compound extracted from the medicinal plant Tripterygium wilfordii Hook F. It exhibits immunosuppressive, anti-inflammatory, and antioxidant activities. Cisplatin is a commonly used chemotherapeutic drug in the treatment of a wide range of tumors. Although very effective therapeutically, it can cause nephrotoxicity leading to dose reduction or discontinuation of treatment. This study aims to clarify the therapeutic potential of celastrol in cisplatin-induced nephrotoxicity. The possible protective effects of celastrol pretreatment against cisplatin-induced oxidative stress and genotoxicity were investigated. A rat kidney epithelial cell line NRK-52E was pretreated with the desired concentrations of celastrol (200 nM, 100 nM, and 50 nM) for 24 h. The cells were treated with 50 μM cisplatin for a further 24 h to see whether cisplatin caused the same or less toxicity compared to the vehicle control group. Alkaline comet assay was performed for genotoxicity assessment. Genotoxicity evaluation revealed that celastrol caused a statistically significant reduction in DNA damage. Oxidative stress parameters were evaluated by measuring the glutathione (GSH) and protein carbonyl (PC) levels and also by measuring the enzyme activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) enzymes. Celastrol pretreatment increased the GSH content of the cells and ameliorated the protein carbonylation level. Likewise, celastrol pretreatment improved the GR and CAT activities. However, no significant difference was observed in GPx and SOD activities. In the light of these findings, celastrol treatment could be a therapeutic option to reduce cisplatin-induced nephrotoxicity. Further studies are needed for the clarification of its therapeutic potential.

scholarly journals Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhuxi Liu ◽  
Caiqin Li ◽  
Xuelian Fan ◽  
Yifang Kuang ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Nicotinamide Adenine Dinucleotide ◽  
Restraint Stress ◽  
Treatment Method ◽  
Sirtuin 1 ◽  
Potential Treatment ◽  
Vitamin B3 ◽  
Dependent Protein ◽  
Protein Deacetylase

AbstractSirtuin 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-h-restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether NAM was capable of attenuating depressive behaviors through inhibiting SIRT1 activity. Surprisingly, the application of NAM significantly reversed the depressive behaviors but increased SIRT1 activity further. In contrast, the level of adenosine triphosphate (ATP) was reduced in the restraint model for depression, and recovered by the administration of NAM. Furthermore, the Sirt1flox/flox; Nestin-Cre mice exhibited antidepressant behaviors and increased ATP levels. These data suggest that ATP plays an important role in depression pathogenesis, and NAM could be a potential treatment method for depression by regulating ATP independent of SIRT1 activity.

scholarly journals The effects of bilingualism on hippocampal volume in ageing bilinguals

2022 ◽  
Author(s):  
Toms Voits ◽  
Holly Robson ◽  
Jason Rothman ◽  
Christos Pliatsikas
Keyword(s):  
Second Language ◽  
Language Learning ◽  
Memory Performance ◽  
Hippocampal Volume ◽  
Older Age ◽  
Protective Effects ◽  
Older Individuals ◽  
Neuroprotective Effects ◽  
Wide Range

AbstractLong-term management of more than one language has been argued to contribute to changes in brain and cognition. This has been particularly well documented in older age, where bilingualism has been linked to protective effects against neurocognitive decline. Since memory difficulties are key aspects of this decline, herein we examine potential effects of bilingualism on the hippocampus, a brain structure related to memory that is particularly vulnerable to cognitive ageing. Hippocampal volume has been shown to increase as a result of second language learning and use in younger adults. However, it is unknown if this is maintained throughout the lifespan. We examine hippocampal volume and episodic memory performance in a participant sample consisting of healthy older individuals with a wide range of experiences in exposure and using a second language. Results reveal greater hippocampal volume calibrated to degree of quantified dual language use. Our results mirror those of immersive active bilingualism in younger populations, suggesting that long-term active bilingualism leads to neuroprotective effects in the hippocampus. We discuss this in the context of literature proposing bilingualism-induced brain reserve in the older age.

scholarly journals Where in the cell is SIRT3? – functional localization of an NAD+-dependent protein deacetylase

2008 ◽  
Vol 411 (2) ◽  
pp. e11-e13 ◽  
Author(s):  
William C. Hallows ◽  
Brittany N. Albaugh ◽  
John M. Denu
Keyword(s):  
Nuclear Localization ◽  
The Elderly ◽  
Active Protein ◽  
Cellular Processes ◽  
Age Related ◽  
Biochemical Journal ◽  
Wide Range ◽  
Functional Localization ◽  
Dependent Protein ◽  
Protein Deacetylase

Sirtuins are NAD+-dependent enzymes that have been implicated in a wide range of cellular processes, including pathways that affect diabetes, cancer, lifespan and Parkinson's disease. To understand their cellular function in these age-related diseases, identification of sirtuin targets and their subcellular localization is paramount. SIRT3 (sirtuin 3), a human homologue of Sir2 (silent information regulator 2), has been genetically linked to lifespan in the elderly. However, the function and localization of this enzyme has been keenly debated. A number of reports have indicated that SIRT3, upon proteolytic cleavage in the mitochondria, is an active protein deacetylase against a number of mitochondrial targets. In stark contrast, some reports have suggested that full-length SIRT3 exhibits nuclear localization and histone deacetylase activity. Recently, a report comparing SIRT3−/− and SIRT+/+ mice have provided compelling evidence that endogenous SIRT3 is mitochondrial and appears to be responsible for the majority of protein deacetylation in this organelle. In this issue of the Biochemical Journal, Cooper et al. present additional results that address the mitochondrial and nuclear localization of SIRT3. Utilizing fluorescence microscopy and cellular fractionation studies, Cooper et al. have shown that SIRT3 localizes to the mitochondria and is absent in the nucleus. Thus this study provides additional evidence to establish SIRT3 as a proteolytically modified, mitochondrial deacetylase.

scholarly journals Chronic Dysuria Following Ginger (Zingiber officinale) Use: A Case Report

2018 ◽  
Vol 7 ◽  
pp. e1086
Author(s):  
Elham Akbarzadeh ◽  
Mojtaba Heydari ◽  
Fatemeh Atarzadeh ◽  
Amir Mohammad Jaladat
Keyword(s):  
Case Report ◽  
Zingiber Officinale ◽  
Flank Pain ◽  
Herbal Remedies ◽  
High Dose ◽  
Wide Range ◽  
Medical Referrals ◽  
Urinary Stream ◽  
History Of

Background: Although ginger is considered a harmless remedial substance for a wide range of medical complaints, according to Persian medicinal texts, its long-term or high-dose consumption is potentially harmful. Case Report: The case of a 43-year-old man, with a complaint of urinary stream interruption, dysuria, and flank pain, following a non-prescribed use of ginger was reported. The symptoms were reported to persist for four years, despite some medical referrals. Remarkably, the symptoms were attested to be shrinking eight weeks after ginger-intake cessation; besides, no further intervention was asserted. Conclusion: The history of herbal remedies use should be considered in patients with any unexplained urinary symptoms. [GMJ.2018;7:e1086]

scholarly journals Salvia miltiorrhizaInjection Ameliorates Renal Damage Induced by Lead Exposure in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lei Li ◽  
Yuanyuan Zhang ◽  
Juanjuan Ma ◽  
Weichong Dong ◽  
Qiongtao Song ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Salvia Miltiorrhiza ◽  
Kidney Injury ◽  
Serum Levels ◽  
Organ Injury ◽  
Therapeutic Drug ◽  
High Dose ◽  
Protective Effects ◽  
Pb Accumulation ◽  
And Function

Exposure to lead (Pb) can induce kidney injury and our recent studies have found thatSalvia miltiorrhiza(SM) injection, a traditional Chinese medicine, could protect against the organ injury induced by iron overload. This study was designed to investigate the protective effects of SM injection on nephrotoxicity induced by Pb acetate in mice and to elucidate the potential mechanism(s). Healthy male mice were randomly divided into four groups: control, Pb, low-doseSalvia miltiorrhiza(L-SM), and high-doseSalvia miltiorrhiza(H-SM). SM injection dose dependently reduced the Pb accumulation in the kidney, decreased kidney coefficients, and ameliorated renal structure and function from the morphology analysis. Meanwhile, SM administration downregulated serum levels of blood urea nitrogen (BUN) and creatinine (CR), decreased malondialdehyde (MAD) content, and increased activities of super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the kidney homogenate. Moreover, SM injection reduced the level of renal apoptosis by immunohistochemical staining analysis. Our findings implicate the therapeutic potential of SM injection for Pb-induced nephrotoxicity, which were at least partly due to the decrease of Pb accumulation, inhibition of lipid peroxidation, and suppression of renal apoptosis. These results provided preliminary experimental support for Danshen as a therapeutic drug for Pb poisoning diseases.

scholarly journals Oral pravastatin prolongs survival time of scrapie-infected mice

2009 ◽  
Vol 90 (7) ◽  
pp. 1775-1780 ◽  
Author(s):  
Vito Vetrugno ◽  
Michele Angelo Di Bari ◽  
Romolo Nonno ◽  
Maria Puopolo ◽  
Claudia D'Agostino ◽  
...  
Keyword(s):  
Water Solubility ◽  
Cholesterol Biosynthesis ◽  
Term Treatment ◽  
Lipid Lowering ◽  
High Dose ◽  
Protective Effects ◽  
Survival Times ◽  
Beneficial Effects ◽  
Long Term Treatment

Statins are potent inhibitors of HMG–CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase in the cholesterol-biosynthesis pathway. They are either lipophilic (e.g. simvastatin) or hydrophilic [e.g. pravastatin (PRV)] compounds, considered mainly for long-term treatment of hypercholesterolaemic individuals. Beneficial effects of statins are not related exclusively to their lipid-lowering action; they also possess cholesterol-independent, pleiotropic effects (e.g. anti-inflammatory and antioxidant). Recent studies revealed that simvastatin treatment increased survival significantly in scrapie-infected mice. Although PRV treatment results in measurable drug levels in the mouse brain, the anti-prion effect of this compound has not been investigated. Therefore, we aimed to test the potential therapeutic action of PRV in a murine scrapie model. Our study showed that high-dose and long-term oral PRV treatment prolonged survival times of strain 139A scrapie-infected mice significantly (194 versus 177 days) in the absence of any obvious toxicity, suggesting that protective effects of statins may be independent of absolute solvent or water solubility of the drug.

scholarly journals Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice

2020 ◽  
Author(s):  
Zhuxi Liu ◽  
Caiqin Li ◽  
Xuelian Fan ◽  
Yifang Kuang ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Nicotinamide Adenine Dinucleotide ◽  
Restraint Stress ◽  
Treatment Method ◽  
Potential Treatment ◽  
Vitamin B3 ◽  
Potential Inhibitor ◽  
Dependent Protein ◽  
Protein Deacetylase

Abstract Sirtuins 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-hour restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether NAM was capable of attenuating depressive behaviors through inhibiting SIRT1 activity. Surprisingly, the application of NAM significantly reversed the depressive behaviors but increased SIRT1 activity further. In contrast, the level of ATP was reduced in the restraint model for depression, and recovered by the administration of NAM. Furthermore, Sirt1−/− mice exhibited antidepressant behaviors and increased ATP levels. These data suggest that ATP plays an important role in depression pathogenesis, and NAM could be a potential treatment method for depression by regulating ATP independent of Sirt1 activity.

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