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01-02-2021 | Agomelatine | Original Article

Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity

Authors: Fatma Nihan Cankara, Caner Günaydın, Zülfinaz Betül Çelik, Yasemin Şahin, Şakir Pekgöz, Yalçın Erzurumlu, Kanat Gülle

Published in: Metabolic Brain Disease | Issue 2/2021

Abstract

Neurotoxicity caused by cisplatin is a major obstacle during chemotherapy. Oxidative stress and inflammation are considered the primary mechanism behind neuronal damage which affects the continuing chemotherapy regimen. Agomelatine was recently described as a neuroprotective compound against toxic insults in the nervous systems. It is an analog of the well-known antioxidant and anti-inflammatory compound melatonin and currently used for depression and sleep disturbances. In the current study, we investigated the possible neuroprotective role of agomelatine against cisplatin-induced oxidative, inflammatory, and behavioral alterations in male rats. Our results show that agomelatine prevented cisplatin-induced neurotoxicity in the HT-22 mouse hippocampal neuronal cell line. Additionally, agomelatine treatment inhibited cisplatin-induced behavioral deficits and neuronal integrity in vivo. For the evaluation of the effect of agomelatine on oxidative stress and inflammation, GSH, MDA, TNF, and IL-6 levels were analyzed in HT-22 cells and hippocampal tissues. Agomelatine significantly attenuated oxidative stress and inflammation due to the cisplatin insult in vitro and in vivo. Also, agomelatine treatment ameliorated the neuronal pathology in the hippocampus, which is strongly related to cognition and memory. Taken together, our results indicate that in males, the neuroprotective effect of agomelatine is mediated through its antioxidant and anti-inflammatory actions abrogating functional deficits.

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Abdel-Wahab WM, Moussa FI (2019) Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation. Drug Des Devel Ther 13:1155–1162. https://doi.org/10.2147/DDDT.S191240CrossRefPubMedPubMedCentral

Aguiar CCT, Almeida AB, Araújo PVP et al (2013) Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures. Cell Mol Neurobiol 33:825–835. https://doi.org/10.1007/s10571-013-9949-0CrossRefPubMed

Akman T, Akman L, Erbas O et al (2015) The preventive effect of oxytocin to Cisplatin-induced neurotoxicity: an experimental rat model. Biomed Res Int 2015:167235. https://doi.org/10.1155/2015/167235CrossRefPubMedPubMedCentral

Alston M, Cain SW, Rajaratnam SMW (2019) Advances of melatonin-based therapies in the treatment of disturbed sleep and mood. Handb Exp Pharmacol 253:305–319. https://doi.org/10.1007/164_2018_139

Atik B, Erkutlu I, Tercan M et al (2011) The effects of exogenous melatonin on peripheral nerve regeneration and collagen formation in rats. J Surg Res 166:330–336. https://doi.org/10.1016/j.jss.2009.06.002CrossRefPubMed

Aygun H, Gul SS (2019) Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: A renal scintigraphy and biochemical study. Bratislava Med J 120:113–118. https://doi.org/10.4149/BLL_2019_018CrossRef

Bathina S, Das UN (2015) Brain-derived neurotrophic factor and its clinical Implications. Arch Med Sci 11:1164–1178. https://doi.org/10.5114/aoms.2015.56342CrossRefPubMedPubMedCentral

Chen WY, Giobbie-Hurder A, Gantman K et al (2014) A randomized, placebo-controlled trial of melatonin on breast cancer survivors: Impact on sleep, mood, and hot flashes. Breast Cancer Res Treat 145:381–388. https://doi.org/10.1007/s10549-014-2944-4CrossRefPubMedPubMedCentral

Chumboatong W, Thummayot S, Govitrapong P et al (2017) Neuroprotection of agomelatine against cerebral ischemia/reperfusion injury through an antiapoptotic pathway in rat. Neurochem Int 102:114–122. https://doi.org/10.1016/j.neuint.2016.12.011CrossRefPubMed

Cipriani A, Furukawa TA, Salanti G et al (2018) Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 391:1357–1366. https://doi.org/10.1016/S0140-6736(17)32802-7CrossRefPubMedPubMedCentral

De Berardis D, Brucchi M, Serroni N et al (2014) Successful use of agomelatine in the treatment of major depression in a woman taking tamoxifen: a case report. Clin Neuropharmacol 37:31–33. https://doi.org/10.1097/WNF.0000000000000009CrossRefPubMed

de Mello AH, Souza L, Cereja RACM, et al (2016) Effect of subchronic administration of agomelatine on brain energy metabolism and oxidative stress parameters in rats. Psychiatry Clin Neurosci 70:159–166. https://doi.org/10.1111/pcn.12371CrossRefPubMed

Demirdaş A, Nazıroğlu M, Ünal G (2016) Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression. Metab Brain Dis 31:1445–1453. https://doi.org/10.1007/s11011-016-9874-2CrossRefPubMed

Guardiola-Lemaitre B, De Bodinat C, Delagrange P et al (2014) Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties. Br J Pharmacol 171:3604–3619. https://doi.org/10.1111/bph.12720CrossRefPubMedPubMedCentral

Gumuslu E, Mutlu O, Sunnetci D et al (2014) The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights 2014:11–21. https://doi.org/10.4137/DTI.S13870CrossRef

Gupta S, Singh P, Sharma B, Sharma B (2015) Neuroprotective effects of agomelatine and vinpocetine against chronic cerebral hypoperfusion induced vascular dementia. Curr Neurovasc Res 12:240–252. https://doi.org/10.2174/1567202612666150603130235CrossRefPubMed

Jabbarpour Z, Shahidi S, Saidijam M et al (2014) Effect of tempol on the passive avoidance and novel object recognition task in diabetic rats. Brain Res Bull 101:51–56. https://doi.org/10.1016/j.brainresbull.2013.12.013CrossRefPubMed

Kany S, Vollrath JT, Relja B (2019) Cytokines in inflammatory disease. Int J Mol Sci 20:6008. https://doi.org/10.3390/ijms20236008CrossRefPubMedCentral

Karakus E, Halici Z, Albayrak A et al (2013) Agomelatine: An antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats. Hum Exp Toxicol 32:846–857. https://doi.org/10.1177/0960327112472994CrossRefPubMed

Krarup-Hansen A, Helweg-Larsen S, Schmalbruch H et al (2007) Neuronal involvement in cisplatin neuropathy: prospective clinical and neurophysiological studies. Brain 130:1076–1088. https://doi.org/10.1093/brain/awl356CrossRefPubMed

Li Y, Zheng M, Kumar Sah S et al (2019) Neuroprotective influence of sitagliptin against cisplatin-induced neurotoxicity, biochemical and behavioral alterations in Wistar rats. Mol Cell Biochem 455:91–97. https://doi.org/10.1007/s11010-018-3472-zCrossRefPubMed

Liu J, Clough SJ, Hutchinson AJ et al (2016) MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol 56:361–383. https://doi.org/10.1146/annurev-pharmtox-010814-124742CrossRefPubMed

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275. https://doi.org/10.1016/0922-338X(96)89160-4CrossRefPubMed

Mehta RD, Roth AJ (2015) Psychiatric considerations in the oncology setting. CA Cancer J Clin 65:299–314. https://doi.org/10.3322/caac.21285CrossRef

Ognjanovic B, Djordjevic N, Matic M, Obradović J (2012) Lipid peroxidative damage on Cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium. Int J Mol Sci 13:1790–1803. https://doi.org/10.3390/ijms13021790CrossRefPubMedPubMedCentral

Yao K, Zhao Y, Zu H (2019) Melatonin receptor stimulation by agomelatine prevents Aβ-induced tau phosphorylation and oxidative damage in PC12 cells. Drug Des Devel Ther 13:387–396. https://doi.org/10.2147/DDDT.S182684CrossRefPubMedPubMedCentral

Zhu J, Carozzi VA, Reed N et al (2016) Ethoxyquin provides neuroprotection against cisplatin-induced neurotoxicity. Sci Rep 6:28861. https://doi.org/10.1038/srep28861CrossRefPubMedPubMedCentral

Title: Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity
Authors: Fatma Nihan Cankara
Caner Günaydın
Zülfinaz Betül Çelik
Yasemin Şahin
Şakir Pekgöz
Yalçın Erzurumlu
Kanat Gülle
Publication date: 01-02-2021
Publisher: Springer US
Keyword: Agomelatine
Published in: Metabolic Brain Disease / Issue 2/2021
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-020-00634-y

At a glance: The STEP trials

Springer Medicine

Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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