Login Register Cart 0
Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Evaluating the Antidepressant-like Properties of Melatonin and Vitamin D3 Combination in Mice Subjected to Restraint Stress: Investigating the Involvement of Oxidative Stress

Author(s): Saeed Mehrzadi, Asieh Hosseini, Shokoufeh Hassani, Fahime Azimirad and Azam Hosseinzadeh*

Volume 19, Issue 4, 2024

Published on: 16 August, 2023

Page: [470 - 479] Pages: 10

DOI: 10.2174/1574885518666230811121026

Price: $65

conference banner
Abstract

Background: Increased levels of oxidative stress are connected with depression. Due to the melatonin's antioxidant effects and Vitamin D3 (Vit D3)'s regulatory effect on the biosynthesis of neurotransmitters and neurotrophic factors, the present study investigated the possible protective effect of melatonin and Vit D3 combination on restraint stress-induced depression-like behaviors in mice.

Methods: After being subjected to restraint stress, mice were divided into six groups using a randomization process. These groups included non-stressed and stressed vehicle-treated groups, as well as groups treated with Vit D3 (25 μg/kg/day), melatonin (10 mg/kg) or fluoxetine. A group also received a combination of both melatonin and Vit D3. The Forced Swimming Test (FST), and Open Field Test (OFT) were conducted to evaluate behavioural changes. The Malondialdehyde (MDA) level and Catalase (CAT), Superoxide Dismutase (SOD) activity, and ADP/ATP ratio were evaluated in the hippocampus of mice.

Results: Restraint stress lengthened the immobility period in FST, while melatonin, Vit D3, and their combination all significantly reversed this impact. Co-administration of melatonin and Vit D3 was more effective than melatonin or Vit D3 administration alone at reducing immobility time. The exposure of mice to restraint stress has been linked to an elevation in the ADP/ATP ratio and oxidative stress in their hippocampus; however, these effects are reversed by the administration of melatonin and Vit D3 (10 mg/kg) alone or in combination. Melatonin and Vit D3 combination increased the hippocampus CAT activity compared with melatonin and Vit D3 alone.

Conclusion: The current study's findings suggested that Vit D3 may enhance melatonin's potential as an antidepressant in FST.

Keywords: Depression, pharmacology, melatonin, vitamin D3, forced swimming test, antidepressant.

« Previous Next »
Graphical Abstract

[1]
Bathina KC, ten Thij M, Lorenzo-Luaces L, Rutter LA, Bollen J. Individuals with depression express more distorted thinking on social media. Nat Hum Behav 2021; 5(4): 458-66.
[http://dx.doi.org/10.1038/s41562-021-01050-7] [PMID: 33574604]
[2]
Andrade L, Caraveo-anduaga JJ, Berglund P, et al. The epidemiology of major depressive episodes: Results from the International Consortium of Psychiatric Epidemiology (ICPE) surveys. Int J Methods Psychiatr Res 2003; 12(1): 3-21.
[http://dx.doi.org/10.1002/mpr.138] [PMID: 12830306]
[3]
Lange KW, Nakamura Y, Lange KM, Zhao H. Tea and depression. Food Sci Hum Wellness 2022; 11(3): 476-82.
[http://dx.doi.org/10.1016/j.fshw.2021.12.032]
[4]
Vaváková M, Ďuračková Z, Trebatická J. Markers of oxidative stress and neuroprogression in depression disorder. Oxid Med Cell Longev 2015; 2015: 1-12.
[http://dx.doi.org/10.1155/2015/898393] [PMID: 26078821]
[5]
Islam MR, Ali S, Karmoker JR, et al. Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder. BMC Psychiatry 2020; 20(1): 333.
[http://dx.doi.org/10.1186/s12888-020-02738-2] [PMID: 32580709]
[6]
Al-harbi KS. Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Prefer Adherence 2012; 6: 369-88.
[http://dx.doi.org/10.2147/PPA.S29716] [PMID: 22654508]
[7]
ÇAMÇİ M, ERDİNÇ M, KELLE I, et al. The effects of melatonin, fluoxetine and their combinations on stress induced behavioral and cognitive impairments in mice. J Fac Pharm Ankara 2023; 47(1): 120-32.
[8]
Caruso G, Grasso M, Fidilio A, et al. Antioxidant activity of fluoxetine and vortioxetine in a non-transgenic animal model of alzheimer’s disease. Front Pharmacol 2021; 12: 809541.
[http://dx.doi.org/10.3389/fphar.2021.809541] [PMID: 35002742]
[9]
Liu T, Zhong S, Liao X, et al. A meta-analysis of oxidative stress markers in depression. PLoS One 2015; 10(10): e0138904.
[http://dx.doi.org/10.1371/journal.pone.0138904] [PMID: 26445247]
[10]
Bakunina N, Pariante CM, Zunszain PA. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology 2015; 144(3): 365-73.
[http://dx.doi.org/10.1111/imm.12443] [PMID: 25580634]
[11]
Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012; 2012: 428010.
[http://dx.doi.org/10.1155/2012/428010]
[12]
Juybari KB, Hosseinzadeh A, Ghaznavi H, et al. Melatonin as a modulator of degenerative and regenerative signaling pathways in injured retinal ganglion cells. Curr Pharm Des 2019; 25(28): 3057-73.
[http://dx.doi.org/10.2174/1381612825666190829151314] [PMID: 31465274]
[13]
Shahriari M, Mehrzadi S, Naseripour M, et al. Beneficial effects of melatonin and atorvastatin on retinopathy in streptozocin-induced diabetic rats. Curr Drug Ther 2020; 15(4): 396-403.
[http://dx.doi.org/10.2174/1574885514666191204104925]
[14]
Pourhanifeh MH, Kamali M, Mehrzadi S, Hosseinzadeh A. Melatonin and neuroblastoma: A novel therapeutic approach. Mol Biol Rep 2021; 48(5): 4659-65.
[http://dx.doi.org/10.1007/s11033-021-06439-1] [PMID: 34061325]
[15]
Mehrzadi S, Karimi MY, Fatemi A, Reiter RJ, Hosseinzadeh A. SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: Beneficial effects of melatonin. Pharmacol Ther 2021; 224: 107825.
[http://dx.doi.org/10.1016/j.pharmthera.2021.107825] [PMID: 33662449]
[16]
Dehdashtian E, Hosseinzadeh A, Hemati K, Karimi MY, Fatemi I, Mehrzadi S. Anti-convulsive effect of thiamine and melatonin combination in mice: Involvement of oxidative stress. Cent Nerv Syst Agents Med Chem 2021; 21(2): 125-9.
[http://dx.doi.org/10.2174/1871524921666210623161212] [PMID: 34165417]
[17]
Hosseinzadeh A, Kamrava SK, Moore BCJ, et al. Molecular aspects of melatonin treatment in tinnitus: A review. Curr Drug Targets 2019; 20(11): 1112-28.
[http://dx.doi.org/10.2174/1389450120666190319162147] [PMID: 30892162]
[18]
Melo MCA, Abreu RLC, Linhares Neto VB, de Bruin PFC, de Bruin VMS. Chronotype and circadian rhythm in bipolar disorder: A systematic review. Sleep Med Rev 2017; 34: 46-58.
[http://dx.doi.org/10.1016/j.smrv.2016.06.007] [PMID: 27524206]
[19]
Ogłodek EA, Just MJ, Szromek AR, Araszkiewicz A. Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity. Pharmacol Rep 2016; 68(5): 945-51.
[http://dx.doi.org/10.1016/j.pharep.2016.04.003] [PMID: 27367919]
[20]
Sundberg I, Ramklint M, Stridsberg M, Papadopoulos FC, Ekselius L, Cunningham JL. Salivary melatonin in relation to depressive symptom severity in young adults. PLoS One 2016; 11(4): e0152814.
[http://dx.doi.org/10.1371/journal.pone.0152814] [PMID: 27042858]
[21]
Stefanovic B, Spasojevic N, Jovanovic P, Dronjak S. Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression. Can J Physiol Pharmacol 2019; 97(7): 685-90.
[http://dx.doi.org/10.1139/cjpp-2018-0612] [PMID: 30773040]
[22]
Littlejohns TJ, Kos K, Henley WE, Kuźma E, Llewellyn DJ. Vitamin D and dementia. J Prev Alzheimers Dis 2016; 3(1): 43-52.
[PMID: 29214280]
[23]
Nikoui V, Ostadhadi S, Azhand P, et al. The effect of nitrazepam on depression and curiosity in behavioral tests in mice: The role of potassium channels. Eur J Pharmacol 2016; 791: 369-76.
[http://dx.doi.org/10.1016/j.ejphar.2016.09.017] [PMID: 27615446]
[24]
Yang W, Wang H. 5, 7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels. Saudi J Biol Sci 2016; 25(2): 253-8.
[PMID: 29472774]
[25]
Farhan M, Haleem DJ. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress. Saudi Pharm J 2016; 24(5): 571-8.
[http://dx.doi.org/10.1016/j.jsps.2015.03.006] [PMID: 27752230]
[26]
Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229(2): 327-36.
[PMID: 596982]
[27]
Ghafour-boroujerdi E, Rahmani S, Sanadgol N, Baeeri M, Hassani S. Investigation of alpha-lipoic acid effect on memory impairment considering strain-dependent differences in mice. Life Sci 2021; 281: 119766.
[http://dx.doi.org/10.1016/j.lfs.2021.119766] [PMID: 34186041]
[28]
Rehman MU, Ghazanfar S, Ul Haq R, et al. Probiotics (bacillus clausii and lactobacillus fermentum NMCC-14) ameliorate stress behavior in mice by increasing monoamine levels and mRNA expression of dopamine receptors (D1 and D2) and synaptophysin. Front Pharmacol 2022; 13: 915595.
[http://dx.doi.org/10.3389/fphar.2022.915595] [PMID: 35928261]
[29]
Tang Y, Wang H, Nie K, et al. Traditional herbal formula Jiao-tai-wan improves chronic restrain stress-induced depression-like behaviors in mice. Biomed Pharmacother 2022; 153: 113284.
[http://dx.doi.org/10.1016/j.biopha.2022.113284] [PMID: 35717786]
[30]
Pourhanifeh MH, Dehdashtian E, Hosseinzadeh A, Sezavar SH, Mehrzadi S. Clinical application of melatonin in the treatment of cardiovascular diseases: Current evidence and new insights into the cardioprotective and cardiotherapeutic properties. Cardiovasc Drugs Ther 2020; 36(1): 131-55.
[PMID: 32926271]
[31]
Ding K, Wang H, Xu J, et al. Melatonin stimulates antioxidant enzymes and reduces oxidative stress in experimental traumatic brain injury: The Nrf2–ARE signaling pathway as a potential mechanism. Free Radic Biol Med 2014; 73: 1-11.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.04.031] [PMID: 24810171]
[32]
Mehrzadi S, Pourhanifeh MH, Mirzaei A, Moradian F, Hosseinzadeh A. An updated review of mechanistic potentials of melatonin against cancer: Pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress. Cancer Cell Int 2021; 21(1): 188.
[http://dx.doi.org/10.1186/s12935-021-01892-1] [PMID: 33789681]
[33]
De Berardis D, Di Iorio G, Acciavatti T, Conti C, Serroni N, Olivieri L, et al. The emerging role of melatonin agonists in the treatment of major depression: Focus on agomelatine. CNS Neurol Disord Drug Targets 2011; 10(1): 119-32.
[http://dx.doi.org/10.2174/187152711794488674]
[34]
Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in the treatment of delayed sleep phase syndrome. Sleep Med 2010; 11(2): 131-6.
[http://dx.doi.org/10.1016/j.sleep.2009.07.013] [PMID: 20044310]
[35]
Hansen MV, Andersen LT, Madsen MT, et al. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: A randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat 2014; 145(3): 683-95.
[http://dx.doi.org/10.1007/s10549-014-2962-2] [PMID: 24756186]
[36]
Arioz BI, Tastan B, Tarakcioglu E, et al. Melatonin attenuates LPS-induced acute depressive-like behaviors and microglial NLRP3 inflammasome activation through the SIRT1/Nrf2 pathway. Front Immunol 2019; 10: 1511.
[http://dx.doi.org/10.3389/fimmu.2019.01511] [PMID: 31327964]
[37]
Hirsch-Rodriguez E, Imbesi M, Manev R, Uz T, Manev H. The pattern of melatonin receptor expression in the brain may influence antidepressant treatment. Med Hypotheses 2007; 69(1): 120-4.
[http://dx.doi.org/10.1016/j.mehy.2006.11.012] [PMID: 17197111]
[38]
Xu Y, Liang L. Vitamin D3/vitamin D receptor signaling mitigates symptoms of post-stroke depression in mice by upregulating hippocampal BDNF expression. Neurosci Res 2021; 170: 306-13.
[http://dx.doi.org/10.1016/j.neures.2020.08.002] [PMID: 32882254]
[39]
Hansen JP, Pareek M, Hvolby A, et al. Vitamin D3 supplementation and treatment outcomes in patients with depression (D3-vitdep). BMC Res Notes 2019; 12(1): 203.
[http://dx.doi.org/10.1186/s13104-019-4218-z] [PMID: 30944021]
[40]
Vaziri F, Nasiri S, Tavana Z, Dabbaghmanesh MH, Sharif F, Jafari P. A randomized controlled trial of vitamin D supplementation on perinatal depression: In Iranian pregnant mothers. BMC Pregnancy Childbirth 2016; 16(1): 239.
[http://dx.doi.org/10.1186/s12884-016-1024-7] [PMID: 27544544]
[41]
Alavi NM, Khademalhoseini S, Vakili Z, Assarian F. Effect of vitamin D supplementation on depression in elderly patients: A randomized clinical trial. Clin Nutr 2019; 38(5): 2065-70.
[http://dx.doi.org/10.1016/j.clnu.2018.09.011] [PMID: 30316534]
[42]
Amini S, Amani R, Jafarirad S, Cheraghian B, Sayyah M, Hemmati AA. The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: A randomized double-blind clinical trial. Nutr Neurosci 2022; 25(1): 22-32.
[http://dx.doi.org/10.1080/1028415X.2019.1707396] [PMID: 31900080]
[43]
Bansal Y, Kuhad A. Mitochondrial dysfunction in depression. Curr Neuropharmacol 2016; 14(6): 610-8.
[http://dx.doi.org/10.2174/1570159X14666160229114755] [PMID: 26923778]
[44]
Anderson G, Reiter RJ. Glioblastoma: Role of mitochondria n-acetylserotonin/melatonin ratio in mediating effects of mir-451 and aryl hydrocarbon receptor and in coordinating wider biochemical changes. Int J Tryptophan Res 2019; 12: 1178646919855942.
[http://dx.doi.org/10.1177/1178646919855942] [PMID: 31244524]
[45]
Suofu Y, Li W, Jean-Alphonse FG, et al. Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proc Natl Acad Sci 2017; 114(38): E7997-8006.
[http://dx.doi.org/10.1073/pnas.1705768114] [PMID: 28874589]
[46]
Carretero M, Escames G, López LC, et al. Long‐term melatonin administration protects brain mitochondria from aging. J Pineal Res 2009; 47(2): 192-200.
[http://dx.doi.org/10.1111/j.1600-079X.2009.00700.x] [PMID: 19573039]
[47]
Latham CM, Brightwell CR, Keeble AR, et al. Vitamin D promotes skeletal muscle regeneration and mitochondrial health. Front Physiol 2021; 12: 660498.
[http://dx.doi.org/10.3389/fphys.2021.660498] [PMID: 33935807]
[48]
Araújo de Lima L, Oliveira Cunha PL, Felicio Calou IB, Tavares Neves KR, Facundo HT. Socorro de Barros viana G. Effects of vitamin D (VD3) supplementation on the brain mitochondrial function of male rats, in the 6-OHDA-induced model of Parkinson’s disease. Neurochem Int 2022; 154: 105280.
[http://dx.doi.org/10.1016/j.neuint.2022.105280] [PMID: 35026378]
[49]
Alamro AA, Al-Malky MM, Ansari MGA, et al. The effects of melatonin and vitamin D3 on the gene expression of BCl-2 and BAX in MCF-7 breast cancer cell line. J King Saud Univ Sci 2021; 33(2): 101287.
[http://dx.doi.org/10.1016/j.jksus.2020.101287]
[50]
Sahakyan G. The role of Vitamin D in treatment of Chronic Insomnia with Melatonin (P5. 320). Neurology 2018; 18.
[51]
Mehrzadi S, Hosseinzadeh A, Dehdashtian E, Jafari-Sabet M. The effects of vitamin D3 and melatonin combination on pentylenetetrazole-induced seizures in mice. Cent Nerv Syst Agents Med Chem 2022; 22(2): 118-24.
[http://dx.doi.org/10.2174/1871524922666220429121253] [PMID: 35507790]
[52]
Menon V, Kar SK, Suthar N, Nebhinani N. Vitamin D and depression: A critical appraisal of the evidence and future directions. Indian J Psychol Med 2020; 42(1): 11-21.
[http://dx.doi.org/10.4103/IJPSYM.IJPSYM_160_19] [PMID: 31997861]
[53]
Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: A pilot study. Psychiatry Res 1998; 77(1): 57-61.
[http://dx.doi.org/10.1016/S0165-1781(97)00128-5] [PMID: 10710176]
[54]
Hickie IB, Rogers NL. Novel melatonin-based therapies: Potential advances in the treatment of major depression. Lancet 2011; 378(9791): 621-31.
[http://dx.doi.org/10.1016/S0140-6736(11)60095-0] [PMID: 21596429]
[55]
Madsen MT, Isbrand A, Andersen UO, et al. The effect of melatonin on depressive symptoms, anxiety, circadian and sleep disturbances in patients after acute coronary syndrome (MEDACIS): Study protocol for a randomized controlled trial. Trials 2017; 18(1): 81.
[http://dx.doi.org/10.1186/s13063-017-1806-x] [PMID: 28228148]
[56]
Targum SD, Wedel PC, Fava M. Changes in cognitive symptoms after a buspirone-melatonin combination treatment for Major depressive disorder. J Psychiatr Res 2015; 68: 392-6.
[http://dx.doi.org/10.1016/j.jpsychires.2015.04.024] [PMID: 26025562]

Rights & Permissions Print Cite
Article Metrics
17
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy