Evaluation of Antidepressive-like Behaviours and Oxidative Stress Parameters in Mice Receiving Imipramine-Zinc Complex Compound

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Sep 28

PMID 37762458

Authors

Aleksandra Szopa

Mariola Herbet

Ewa Poleszak

Anna Serefko

Agnieszka Czylkowska

Iwona Piatkowska-Chmiel

Kamila Kasperek

Andrzej Wrobel

Paulina Prewencka

Bernadeta Szewczyk

Affiliations

Soon will be listed here.

Abstract

The study aimed to evaluate the antidepressant-like effects of an imipramine-zinc (IMI-Zn) complex compound on mice and assess the level of oxidative stress parameters. The research also investigated whether the IMI-Zn complex showed superior antidepressant activity compared to individual treatments of both compounds at effective doses and their joint administration at subtherapeutic doses. The study was conducted on mice. Forced swim (FST), tail suspension (TST), and locomotor activity tests were used for behavioral studies. The results demonstrated the IMI-Zn complex's dose-dependent antidepressant potential when orally administered to mice. Its efficacy was similar to the separate administration of therapeutic doses of imipramine (IMI) and zinc (Zn) and their joint administration at subtherapeutic doses. Moreover, subjecting mice to acute stress did not significantly affect the activity of on glutathione peroxidase (GPX), glutathione reductase (GR), and total antioxidant status (TAS), possibly due to the short exposure time to the stress stimulus. By developing the IMI-Zn complex, it might be possible to simplify the treatment approach, potentially improving patient compliance by combining the therapeutic effects of both IMI and Zn within a single compound, thus addressing one of the contributing factors to non-compliance in depression therapy. The IMI-Zn complex could be a valuable strategy to optimize therapeutic outcomes and balance efficacy and tolerability.

Citing Articles

The Novel Imipramine-Magnesium Complex Exerts Antidepressant-like Activity in Mice Subjected to the Forced Swim Test and the Tail Suspension Test.

Serefko A, Lachowicz-Radulska J, Szopa A, Herbet M, Czylkowska A, Ignatiuk K Molecules. 2025; 30(3).

PMID: 39942624 PMC: 11820773. DOI: 10.3390/molecules30030519.

Regenerative potentials of bone marrow mesenchymal stem cells derived exosomes or its combination with zinc in recovery of degenerated circumvallate papilla following surgical bilateral transection of glossopharyngeal nerve in rats.

Salem E, Rizk H, Abouelela Y, Prince A, Tohamy A, Lasheen N BMC Oral Health. 2024; 24(1):1320.

PMID: 39478548 PMC: 11523770. DOI: 10.1186/s12903-024-05050-7.

References

Mokoena M, Harvey B, Oliver D, Brink C . Ozone modulates the effects of imipramine on immobility in the forced swim test, and nonspecific parameters of hippocampal oxidative stress in the rat. Metab Brain Dis. 2010; 25(2):125-33. DOI: 10.1007/s11011-010-9189-7. View

Halahakoon D, Kieslich K, ODriscoll C, Nair A, Lewis G, Roiser J . Reward-Processing Behavior in Depressed Participants Relative to Healthy Volunteers: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2020; 77(12):1286-1295. PMC: 7391183. DOI: 10.1001/jamapsychiatry.2020.2139. View

Thomas S, Shin M, McInnis M, Bostwick J . Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression. Pharmacotherapy. 2015; 35(4):433-49. DOI: 10.1002/phar.1576. View

Steru L, Chermat R, Thierry B, Simon P . The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985; 85(3):367-70. DOI: 10.1007/BF00428203. View

Maes M, Berk M, Goehler L, Song C, Anderson G, Galecki P . Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med. 2012; 10:66. PMC: 3391987. DOI: 10.1186/1741-7015-10-66. View

Roiser J, Elliott R, Sahakian B . Cognitive mechanisms of treatment in depression. Neuropsychopharmacology. 2011; 37(1):117-36. PMC: 3238070. DOI: 10.1038/npp.2011.183. View

Szewczyk B, Poleszak E, Sowa-Kucma M, Siwek M, Dudek D, Ryszewska-Pokrasniewicz B . Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Pharmacol Rep. 2008; 60(5):588-9. View

Nowak G, Siwek M, Dudek D, Zieba A, Pilc A . Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol. 2004; 55(6):1143-7. View

Rogalewicz B, Szczesio M, Poleszak E, Kowalczyk J, Szewczyk B, Camargo B . Influence of Incorporation of Different d-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties. Int J Mol Sci. 2021; 22(23). PMC: 8657940. DOI: 10.3390/ijms222312909. View

10.

Trivedi M, Thase M, Fava M, Nelson C, Yang H, Qi Y . Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features. J Clin Psychiatry. 2009; 69(12):1928-36. View

11.

Rafalo-Ulinska A, Poleszak E, Szopa A, Serefko A, Rogowska M, Sowa I . Imipramine Influences Body Distribution of Supplemental Zinc Which May Enhance Antidepressant Action. Nutrients. 2020; 12(9). PMC: 7551732. DOI: 10.3390/nu12092529. View

12.

Ranjbar E, Shams J, Sabetkasaei M, M-Shirazi M, Rashidkhani B, Mostafavi A . Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression. Nutr Neurosci. 2013; 17(2):65-71. DOI: 10.1179/1476830513Y.0000000066. View

13.

Rojo J, Ros S, Aguera L, De la Gandara J, de Pedro J . Combined antidepressants: clinical experience. Acta Psychiatr Scand Suppl. 2005; (428):25-31, 36. DOI: 10.1111/j.1600-0447.2005.00677.x. View

14.

Wiersema C, Oude Voshaar R, van den Brink R, Wouters H, Verhaak P, Comijs H . Determinants and consequences of polypharmacy in patients with a depressive disorder in later life. Acta Psychiatr Scand. 2022; 146(1):85-97. PMC: 9321061. DOI: 10.1111/acps.13435. View

15.

Herbet M, Szumelda I, Piatkowska-Chmiel I, Gawronska-Grzywacz M, Dudka J . Beneficial effects of combined administration of fluoxetine and mitochondria-targeted antioxidant at in behavioural and molecular studies in mice model of depression. Behav Brain Res. 2021; 405:113185. DOI: 10.1016/j.bbr.2021.113185. View

16.

Mlyniec K, Davies C, de Aguero Sanchez I, Pytka K, Budziszewska B, Nowak G . Essential elements in depression and anxiety. Part I. Pharmacol Rep. 2014; 66(4):534-44. DOI: 10.1016/j.pharep.2014.03.001. View

17.

Gronli O, Kvamme J, Friborg O, Wynn R . Zinc deficiency is common in several psychiatric disorders. PLoS One. 2013; 8(12):e82793. PMC: 3868572. DOI: 10.1371/journal.pone.0082793. View

18.

Krishnan V, Nestler E . The molecular neurobiology of depression. Nature. 2008; 455(7215):894-902. PMC: 2721780. DOI: 10.1038/nature07455. View

19.

Herbet M, Szopa A, Wosko S, Serefko A, Izdebska M, Gawronska-Grzywacz M . The Positive Synergism of CPT and MK-801 in Behavioral Tests and in Reduction of Environmental Stress and Redox Signaling Changes in Mice Cerebral Cortex. CNS Neurol Disord Drug Targets. 2016; 16(7):837-845. DOI: 10.2174/1871527315666161010152414. View

20.

Bathina S, Das U . Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2016; 11(6):1164-78. PMC: 4697050. DOI: 10.5114/aoms.2015.56342. View