Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis.
Abstract: Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500 μg/kg bw), MIN (50mg/kg bw) or AA (50mg/kg bw). Infected neuroblastoma cultures (MOI: 1); MLT: 0.5, 1, 5mM, MIN: 0.1, 0.2, 2 μM or AA: 25, 50, 75 μM. Brains were obtained at days 1, 3 and 5. In addition, survival rate of infected treated mice was also analyzed. Viral replication was determined by the plaque formation technique. NO and lipid peroxidation were measured by Griess׳ reaction and thiobarbituric acid assay respectively. Increased viral replication, NO production and lipid peroxidation were observed in both, infected brain and neuroblastoma cell cultures compared with uninfected controls. Those effects were diminished by the studied treatments. In addition, increased survival rate (50%) in treated infected animals compared with untreated infected mice (0%) was found. MLT, MIN and AA have an antiviral effect involving their anti-oxidant properties, and suggesting a potential use of these compounds for human VEE virus infection.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication Date: 2015-07-10 PubMed ID: 26168898DOI: 10.1016/j.brainres.2015.06.034Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study explores the impact of melatonin, minocycline and ascorbic acid on the severity of Venezuelan equine encephalitis by observing changes in viral levels, nitric oxide production and oxidative stress. The research indicates these substances could offer potential benefits as a treatment for the virus.
Research Aim and Methodology
- The primary aim of the study was to assess the effectiveness of melatonin, minocycline and ascorbic acid in altering the progression of Venezuelan equine encephalitis virus in mice and neuroblastoma cell cultures.
- These compounds were selected because their antiviral properties have been proven in previous experimental infections. However, the specific mechanisms that generate these antiviral activities haven’t been thoroughly researched.
- In the experiment, infected mice were treated with specific doses of each compound, and their brains were examined after 1, 3 and 5 days.
- The level of viral replication in the mice and cell cultures was monitored using the plaque formation technique.
Findings
- The study found that untreated, infected mouse brains and neuroblastoma cell cultures exhibited an increase in the viral replication, nitric oxide production and lipid peroxidation when compared to uninfected controls.
- These reductions were significantly less in mice and cell cultures that had been treated with melatonin, minocycline or ascorbic acid.
- Futher, the research found that mice infected with the virus and treated with the compounds had a survival rate of 50%, whereas untreated, infected mice had a survival rate of 0%.
Implications of the Study
- The study suggests that the antiviral effect of melatonin, minocycline and ascorbic acid could be due to their antioxidant properties.
- This finding indicates a potential use of these compounds in treating human Venezuelan equine encephalitis virus infections. However, more research is required to determine the specific mechanisms of the antiviral effects as well as to assess potential side effects.
Cite This Article
APA
(2015).
Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis.
Brain Res, 1622, 368-376.
https://doi.org/10.1016/j.brainres.2015.06.034 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Antiviral Agents / pharmacology
- Ascorbic Acid / pharmacology
- Brain / drug effects
- Brain / metabolism
- Cell Line, Tumor
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Encephalitis Virus, Venezuelan Equine / metabolism
- Encephalomyelitis, Venezuelan Equine / drug therapy
- Encephalomyelitis, Venezuelan Equine / metabolism
- Encephalomyelitis, Venezuelan Equine / mortality
- Lipid Peroxidation / drug effects
- Lipid Peroxidation / physiology
- Male
- Melatonin / pharmacology
- Mice
- Minocycline / pharmacology
- Neuroblastoma / drug therapy
- Neuroblastoma / metabolism
- Neuroprotective Agents / pharmacology
- Nitric Oxide / metabolism
- Oxidative Stress / drug effects
- Oxidative Stress / physiology
- Survival Rate
- Treatment Outcome
- Viral Load
Citations
This article has been cited 26 times.- Kitidee K, Samutpong A, Pakpian N, Wisitponchai T, Govitrapong P, Reiter RJ, Wongchitrat P. Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells.. Sci Rep 2023 Apr 13;13(1):6063.
- Kikuchi M, Kadena M, Fukamachi H, Takaki T, Matsui S, Hoashi-Takiguchi S, Morisaki H, Trtić N, Mori M, Kurosawa M, Itsumi M, Funatsu T, Sakurai A, Shintani S, Kato H, Fujita T, Maruoka Y, Kuwata H. Melatonin suppresses the antiviral immune response to EMCV infection through intracellular ATP deprivation caused by mitochondrial fragmentation.. Heliyon 2022 Oct;8(10):e11149.
- Begum R, Mamun-Or-Rashid ANM, Lucy TT, Pramanik MK, Sil BK, Mukerjee N, Tagde P, Yagi M, Yonei Y. Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2.. Molecules 2022 Oct 16;27(20).
- Grudlewska-Buda K, Wiktorczyk-Kapischke N, Budzyńska A, Kwiecińska-Piróg J, Przekwas J, Kijewska A, Sabiniarz D, Gospodarek-Komkowska E, Skowron K. The Variable Nature of Vitamin C-Does It Help When Dealing with Coronavirus?. Antioxidants (Basel) 2022 Jun 24;11(7).
- Gao T, Liu X, Tan K, Zhang D, Zhu B, Ma F, Li C. Introducing melatonin to the horticultural industry: physiological roles, potential applications, and challenges.. Hortic Res 2022;9:uhac094.
- Shokouhi Targhi H, Mehrbod P, Fotouhi F, Amininasab M. In vitro anti-influenza assessment of anionic compounds ascorbate, acetate and citrate.. Virol J 2022 May 23;19(1):88.
- Shahbaz U, Fatima N, Basharat S, Bibi A, Yu X, Hussain MI, Nasrullah M. Role of vitamin C in preventing of COVID-19 infection, progression and severity.. AIMS Microbiol 2022;8(1):108-124.
- Uddin MS, Millat MS, Baral PK, Ferdous M, Uddin MG, Sarwar MS, Islam MS. The protective role of vitamin C in the management of COVID-19: A Review.. J Egypt Public Health Assoc 2021 Dec 11;96(1):33.
- Qiu Y, Ma Y, Jiang M, Li S, Zhang J, Chen H, Xu M, Gao S, Tian L, Tao B, Wang Y, Han D, Cao F. Melatonin Alleviates LPS-Induced Pyroptotic Cell Death in Human Stem Cell-Derived Cardiomyocytes by Activating Autophagy.. Stem Cells Int 2021;2021:8120403.
- Önal H, Arslan B, Üçüncü Ergun N, Topuz Ş, Yilmaz Semerci S, Kurnaz ME, Molu YM, Bozkurt MA, Süner N, Kocataş A. Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial.. Turk J Biol 2021;45(4):518-529.
- Teafatiller T, Agrawal S, De Robles G, Rahmatpanah F, Subramanian VS, Agrawal A. Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells.. Biomolecules 2021 Aug 3;11(8).
- Ramos E, López-Muñoz F, Gil-Martín E, Egea J, Álvarez-Merz I, Painuli S, Semwal P, Martins N, Hernández-Guijo JM, Romero A. The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy.. Antioxidants (Basel) 2021 Jul 20;10(7).
- Cross KM, Landis DM, Sehgal L, Payne JD. Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy.. Endocr Pract 2021 Aug;27(8):850-855.
- Vlachou M, Siamidi A, Dedeloudi A, Konstantinidou SK, Papanastasiou IP. Pineal hormone melatonin as an adjuvant treatment for COVID‑19 (Review).. Int J Mol Med 2021 Apr;47(4).
- Wongchitrat P, Shukla M, Sharma R, Govitrapong P, Reiter RJ. Role of Melatonin on Virus-Induced Neuropathogenesis-A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection.. Antioxidants (Basel) 2021 Jan 2;10(1).
- Mosquera-Sulbaran JA, Hernández-Fonseca H. Tetracycline and viruses: a possible treatment for COVID-19?. Arch Virol 2021 Jan;166(1):1-7.
- Khan ZA, Yumnamcha T, Mondal G, Devi SD, Rajiv C, Labala RK, Sanjita Devi H, Chattoraj A. Artificial Light at Night (ALAN): A Potential Anthropogenic Component for the COVID-19 and HCoVs Outbreak.. Front Endocrinol (Lausanne) 2020;11:622.
- Tan DX, Hardeland R. Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19.. Molecules 2020 Sep 25;25(19).
- Bahrampour Juybari K, Pourhanifeh MH, Hosseinzadeh A, Hemati K, Mehrzadi S. Melatonin potentials against viral infections including COVID-19: Current evidence and new findings.. Virus Res 2020 Oct 2;287:198108.
- Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19).. Front Immunol 2020;11:1451.
- Reiter RJ, Abreu-Gonzalez P, Marik PE, Dominguez-Rodriguez A. Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19.. Front Med (Lausanne) 2020;7:226.
- Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome.. PharmaNutrition 2020 Jun;12:100190.
- Kernbach ME, Newhouse DJ, Miller JM, Hall RJ, Gibbons J, Oberstaller J, Selechnik D, Jiang RHY, Unnasch TR, Balakrishnan CN, Martin LB. Light pollution increases West Nile virus competence of a ubiquitous passerine reservoir species.. Proc Biol Sci 2019 Jul 24;286(1907):20191051.
- Li X, Tong Q, Xie D, Chen Z, Pan S, Zhang X, Dong W. Low serum uric acid levels in patients with acute central nervous system viral infections.. Neuroreport 2017 Dec 13;28(18):1250-1254.
- Quick ED, Seitz S, Clarke P, Tyler KL. Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection.. J Virol 2017 Nov 15;91(22).
- Montiel M, Bonilla E, Valero N, Mosquera J, Espina LM, Quiroz Y, Álvarez-Mon M. Melatonin decreases brain apoptosis, oxidative stress, and CD200 expression and increased survival rate in mice infected by Venezuelan equine encephalitis virus.. Antivir Chem Chemother 2015 Aug;24(3-4):99-108.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
