RECURRENT DEPRESSIVE DISORDER, TYPE 2 DIABETES MELLITUS AND OXIDATIVE STRESS
DOI:
https://doi.org/10.15547/tjs.2025.01.011Keywords:
Oxidative stress, depression, diabetesAbstract
The imbalance between pro-oxidant and antioxidant factors leads to oxidative stress, which seems to play an important role in the pathogenesis of both depression and type 2 diabetes mellitus. Because ROS is an essential mediator for the activation of pro-inflammatory signalling pathways, obesity and hyperglycaemia-induced ROS production may favour the induction of M1-like pro-inflammatory macrophages during the onset and progression of diabetes. By generating more reactive oxygen species (ROS) and upregulating markers of chronic inflammation, hyperglycaemia can lead to vascular dysfunction. Damage to cellular components brought on by an excess of reactive oxygen species (ROS) generates pro-inflammatory molecules such as 4-hydroxynonenal, neoepitopes, and damage-associated molecular patterns, which in turn trigger the immune system and ultimately result in cell death. In MDD, oxidative stress-induced reductions in NO-dependent dilatation and alterations in vascular smooth muscle function are directly associated with microvascular dysfunction.
References
Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763. doi: 10.1155/2017/8416763. Epub 2017 Jul 27. PMID: 28819546; PMCID: PMC5551541.
Ekoue, D.N.; He, C.; Diamond, A.M.; Bonini, M.G. Manganese superoxide dismutase and glutathione peroxidase-1 contribute to the rise and fall of mitochondrial reactive oxygen species which drive oncogenesis. Biochim. Biophys. Acta Bioenerg. 2017, 1858, 628–632.
Sato H., Shibata H., Shimizu T., Shibata S., Toriumi H., Ebine T. Differential cellular localization of antioxidant enzymes in the trigeminal ganglion. Neuroscience. 2013;248:345–358. doi: 10.1016/j.neuroscience.2013.06.010.
Navarro-Yepes J., Zavala-Flores L., Anandhan A., Wang F., Skotak M., Chandra N. Antioxidant gene therapy against neuronal cell death. Pharmacology & Therapeutics. 2014;142:206–230. doi: 10.1016/j.pharmthera.2013.12.007.
Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180-3. doi: 10.1016/j.redox.2015.01.002. Epub 2015 Jan 3. PMID: 25588755; PMCID: PMC4309861.
Al-Gubory K. H., Garrel C., Faure P., Sugino N. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress. Reproductive Biomedicine Online. 2012;25:551–560.
Gutteridge JM, Halliwell B. Comments on review of Free Radicals in Biology and Medicine, by Barry Halliwell and John MC. Gutteridge. Free Radic Biol Med. 1992; 12:93-95.
Raddant AC, Russo AF. Reactive oxygen species induce procalcitonin expression in trigeminal ganglia glia. Headache. 2014 Mar;54(3):472-84. doi: 10.1111/head.12301. Epub 2014 Feb 11. PMID: 24512072; PMCID: PMC3947709.
Rajendran P, Nandakumar N, Rengarajan T, Palaniswami R, Gnanadhas EN, Lakshminarasaiah U, Gopas J, Nishigaki I. Antioxidants and human diseases. Clin Chim Acta. 2014 Sep 25;436:332-47. doi: 10.1016/j.cca.2014.06.004. Epub 2014 Jun 13. PMID: 24933428.
Helmut Sies, in Stress: Physiology, Biochemistry, and Pathology, Handbook of Stress Series, Volume 3 2019, Pages 153-163
Samina Salim Oxidative Stress and the Central Nervous System, Journal of Pharmacology and Experimental Therapeutics January 1, 2017, 360 (1) 201-205; DOI: https://doi.org/10.1124/jpet.116.237503
Grotle AK, Darling AM, Saunders EF, Fadel PJ, Trott DW, Greaney JL. Augmented T-cell mitochondrial reactive oxygen species in adults with major depressive disorder. Am J Physiol Heart Circ Physiol. 2022 Apr 1;322(4):H568-H574. doi: 10.1152/ajpheart.00019.2022. Epub 2022 Feb 18. PMID: 35179977; PMCID: PMC8917910.
Tewari D, Sah AN, Bawari S, Nabavi SF, Dehpour AR, Shirooie S, Braidy N, Fiebich BL, Vacca RA, Nabavi SM. Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition. Curr Neuropharmacol. 2021;19(2):114-126. doi: 10.2174/1570159X18666200429001549. PMID: 32348225; PMCID: PMC8033982.
Kotzaeroglou, A.; Tsamesidis, I. The Role of Equilibrium between Free Radicals and Antioxidants in Depression and Bipolar Disorder. Medicines 2022, 9, 57. https://doi.org/10.3390/medicines9110057
Bouvier E, Brouillard F, Molet J, Claverie D, Cabungcal JH, Cresto N, Doligez N, Rivat C, Do KQ, Bernard C, Benoliel JJ, Becker C. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression. Mol Psychiatry. 2017 Dec;22(12):1701-1713. doi: 10.1038/mp.2016.144. Epub 2016 Sep 20. Erratum in: Mol Psychiatry. 2017 Dec;22(12 ):1795. PMID: 27646262.
Jansen F, Yang X, Franklin BS, Hoelscher M, Schmitz T, Bedorf J, Nickenig G, Werner N. High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation. Cardiovasc Res. 2013 Apr 1;98(1):94-106. doi: 10.1093/cvr/cvt013. Epub 2013 Jan 22. PMID: 23341580.
Butkowski EG, Jelinek HF. Hyperglycaemia, oxidative stress and inflammation markers. Redox Rep. 2017;22:257–264.
Li S, Zheng L, Zhang J, Liu X, Wu Z. Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy. Free Radic Biol Med. 2021 Jan;162:435-449. doi: 10.1016/j.freeradbiomed.2020.10.323. Epub 2020 Nov 2. PMID: 33152439.
Erika Rendra, Vladimir Riabov, Dieuwertje M. Mossel, Tatyana Sevastyanova, Martin C. Harmsen, Julia Kzhyshkowska, Reactive oxygen species (ROS) in macrophage activation and function in diabetes, Immunobiology, Volume 224, Issue 2, 2019, Pages 242-253, ISSN 0171-2985, https://doi.org/10.1016/j.imbio.2018.11.010. (https://www.sciencedirect.com/science/article/pii/S0171298518302134)
K. LUC1, A. SCHRAMM-LUC1, T.J. GUZIK1,2, T.P. MIKOLAJCZYK1,3; OXIDATIVE STRESS AND INFLAMMATORY MARKERS IN PREDIABETES AND DIABETES; JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2019, 70, 6, 809-824 www.jpp.krakow.pl | DOI: 10.26402/jpp.2019.6.01
Chong CR, Clarke K, Levelt E. Metabolic remodelling in diabetic cardiomyopathy. Cardiovasc Res 2017; 113: 422-430.
Wu JQ, Kosten TR, and Zhang XY (2013) Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 46:200–206
Bhatt S, Nagappa AN, Patil CR. Role of oxidative stress in depression. Drug Discov Today. 2020 Jul;25(7):1270-1276. doi: 10.1016/j.drudis.2020.05.001. Epub 2020 May 8. PMID: 32404275.
Fu S, Chen H, Yang W, Xia X, Zhao S, Xu X, Ai P, Cai Q, Li X, Wang Y, Zhu J, Zhang B, Zheng JC. ROS-Targeted Depression Therapy via BSA-Incubated Ceria Nanoclusters. Nano Lett. 2022 Jun 8;22(11):4519-4527. doi: 10.1021/acs.nanolett.2c01334. Epub 2022 May 18. PMID: 35583518; PMCID: PMC9185743.
Bakunina N, Pariante CM, Zunszain PA. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology. 2015 Mar;144(3):365-373. doi: 10.1111/imm.12443. Epub 2015 Jan 10. PMID: 25580634; PMCID: PMC4557673.
Vaváková, M.; ɰuračková, Z.; Trebatická, J. Markers of Oxidative Stress and Neuroprogression in Depression Disorder. Oxid. Med. Cell. Longev. 2015, 2015.
Greaney JL, Saunders EFH, Santhanam L, Alexander LM. Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder. Circ Res. 2019 Feb 15;124(4):564-574. doi: 10.1161/CIRCRESAHA.118.313764. PMID: 30582458; PMCID: PMC6375800.
Gu S, Li Y, Jiang Y, Huang JH, Wang F. Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders. Antioxidants (Basel). 2022 Nov 20;11(11):2296. doi: 10.3390/antiox11112296. PMID: 36421482; PMCID: PMC9687220.
Wei J, Zhang M, Zhou J. Myeloid-derived suppressor cells in major depression patients suppress T-cell responses through the production of reactive oxygen species. Psychiatry Res. 2015 Aug 30;228(3):695-701. doi: 10.1016/j.psychres.2015.06.002. Epub 2015 Jun 10. PMID: 26165964.
Kudlow P, Cha DS, Carvalho AF, McIntyre RS. Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications. Curr Mol Med. 2016;16(2):206-15. doi: 10.2174/1566524016666160126144722. PMID: 26812915.
Bansal Y, Kuhad A. Mitochondrial Dysfunction in Depression. Curr Neuropharmacol. 2016;14(6):610-8. doi: 10.2174/1570159x14666160229114755. PMID: 26923778; PMCID: PMC4981740.
Tatsuta T, Langer T. Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J. 2008. Jan 23;27(2):306–14.
Zhang Y, Xu H. Translational regulation of mitochondrial biogenesis. Biochem Soc Trans. 2016. Dec 15;44(6):1717–1724.
Morita M, Gravel SP, Hulea L, et al. mTOR coordinates protein synthesis, mitochondrial activity and proliferation. Cell Cycle. 2015;14(4):473–80.
Vyas S, Zaganjor E, Haigis MC. Mitochondria and Cancer. Cell. 2016. Jul 28;166(3):555–566.
Abelaira HM, Reus GZ, Neotti MV, et al. The role of mTOR in depression and antidepressant responses. Life Sci. 2014. Apr 17;101(1–2):10–4.
Liu X, Liu X, Wang Y, Zeng B, Zhu B, Dai F. Association between depression and oxidative balance score: National Health and Nutrition Examination Survey (NHANES) 2005-2018. J Affect Disord. 2023 Sep 15;337:57-65. doi: 10.1016/j.jad.2023.05.071. Epub 2023 May 25. PMID: 37244542.
Gautam M, Agrawal M, Gautam M, Sharma P, Gautam AS, Gautam S. Role of antioxidants in generalised anxiety disorder and depression. Indian J Psychiatry. 2012 Jul;54(3):244-7. doi: 10.4103/0019-5545.102424. PMID: 23226848; PMCID: PMC3512361.
Vargas, H. O., Nunes, S. O., Pizzo de Castro, M., Bortolasci, C. C., Sabbatini Barbosa, D., Kaminami Morimoto, H., ... Berk, M. (2013). Oxidative stress andlowered total antioxidant status are associatedwith a historyof suicide attempts. Journal of Affective Disorders, 150(3), 923–930.
Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001 Aug 1;357(Pt 3):593-615. doi: 10.1042/0264-6021:3570593. PMID: 11463332; PMCID: PMC1221991.
McLeod TM, López-Figueroa AL, López-Figueroa MO. Nitric oxide, stress, and depression. Psychopharmacology Bulletin. 2001 ;35(1):24-41. PMID: 12397868.
Montezuma K, Biojone C, Lisboa SF, et al. Inhibition of iNOS induces antidepressant-like effects in mice: pharmacological and genetic evidence. Neuropharmacology. 2012;62:485–491.
Cinelli MA, Do HT, Miley GP, Silverman RB. Inducible nitric oxide synthase: Regulation, structure, and inhibition. Med Res Rev. 2020 Jan;40(1):158-189. doi: 10.1002/med.21599. Epub 2019 Jun 13. PMID: 31192483; PMCID: PMC6908786.
Bun-Hee Lee, Sung-Woo Lee, Dokyung Yoon, Heon-Jeong Lee, Jong-Chul Yang, Se-Hoon Shim, Do-Hoon Kim, Ryu Seung-Ho, Changsu Han, Yong-Ku Kim, Increased plasma nitric oxide metabolites in suicide attempters, Neuropsychobiology 53 (2006) 127–132.
Suzuki E, Yagi G, Nakaki T, Kanba S, Asai M. Elevated plasma nitrate levels in depressive states. J Affect Disord. 2001 Mar;63(1-3):221-4. doi: 10.1016/s0165-0327(00)00164-6. PMID: 11246099.
Dhir, A., & Kulkarni, S. K. (2011). Nitric oxide and major depression. Nitric Oxide, 24(3), 125–131. doi:10.1016/j.niox.2011.02.002
Riveros, M.E.; Ávila, A.; Schruers, K.; Ezquer, F. Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression. Antioxidants 2022, 11, 540. https://doi.org/10.3390/antiox11030540
Lara Onofre Ferriani, Daniela Alves Silva, Maria del Carmen Bisi Molina, José Geraldo Mill, André Russowsky Brunoni, Maria de Jesus Mendes da Fonseca, Arlinda B. Moreno, Isabela M. Benseñor, Odaleia Barbosa de Aguiar, Sandhi Maria Barreto, Maria Carmen Viana, Associations of depression and intake of antioxidants and vitamin B complex: Results of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), Journal of Affective Disorders, Volume 297, 2022, Pages 259-268, ISSN 0165 0327, https://doi.org/10.1016/j.jad.2021.10.027. (https://www.sciencedirect.com/science/article/pii/S0165032721011046)
Michael Maes, Nathalie De Vos, Rosaria Pioli, Paul Demedts, Annick Wauters, Hugo Neels, Armand Christophe, Lower serum vitamin E concentrations in major depression: Another marker of lowered antioxidant defenses in that illness, Journal of Affective Disorders, Volume 58, Issue 3, 2000, Pages 241-246, ISSN 0165-0327, https://doi.org/10.1016/S0165-0327(99)00121-4. (https://www.sciencedirect.com/science/article/pii/S0165032799001214)
Hossein Farhadnejad, Asal Neshatbini Tehrani, Amin Salehpour, Azita Hekmatdoost, Antioxidant vitamin intakes and risk of depression, anxiety and stress among female adolescents, Clinical Nutrition ESPEN, Volume 40, 2020, Pages 257-262, ISSN 2405-4577, https://doi.org/10.1016/j.clnesp.2020.09.010. (https://www.sciencedirect.com/science/article/pii/S2405457720301972)
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