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Published in: Metabolic Brain Disease 6/2016

01-12-2016 | Original Article

Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression

Authors: Arif Demirdaş, Mustafa Nazıroğlu, Gülin Özdamar Ünal

Published in: Metabolic Brain Disease | Issue 6/2016

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Abstract

Agomelatine (AGOM) as an antidepressant acts both as a melatonin-receptor agonist and a selective serotonin-receptor antagonist. As a potent melatonin derived antioxidant, AGOM might modulate depression-induced lipid peroxidation and pro-inflammatory cytokines in brain, kidney and liver. The present study explores whether AGOM protects against experimental depression-induced brain, kidney and liver oxidative stress, and plasma cytokine production in rats with chronic mild stress (CMS)-induced depression. Thirty-six rats were divided into four groups. The first group was used as an untreated control. The second group received AGOM for 4 weeks. The third group was exposed to chronic mild stress (CMS) of 4 weeks for induction depression. The fourth group received 40 mg/kg AGOM and CMS for 4 weeks. Liver and kidney lipid peroxidation levels were high in the CMS group although they were low in AGOM treatments. AGOM and AGOM + CMS treatments increased the lowered glutathione peroxidase activity and reduced glutathione levels in brain, kidney and liver of CMS group. β-carotene, vitamin A and vitamin E concentrations in the brain, kidney and liver of the four groups were not changed by CMS and AGOM treatments. However, plasma TNF-α, interleukin (IL)-1β, and IL-4 levels were high in the CMS and AGOM group and their levels were further increased by the AGOM + CMS treatment. In conclusions, AGOM induced protective effects against experimental depression-induced brain, kidney, and liver oxidative injuries through regulation of the glutathione concentrations and glutathione peroxidase activity. However, plasma cytokine productions were increased by the AGOM treatment.
Literature
go back to reference Akpinar A, Uğuz AC, Nazıroğlu M (2014) Agomelatine and duloxetine synergistically modulates apoptotic pathway by inhibiting oxidative stress triggered intracellular calcium entry in neuronal PC12 cells: role of TRPM2 and voltage-gated calcium channels. J Membr Biol 247:451–459CrossRefPubMed Akpinar A, Uğuz AC, Nazıroğlu M (2014) Agomelatine and duloxetine synergistically modulates apoptotic pathway by inhibiting oxidative stress triggered intracellular calcium entry in neuronal PC12 cells: role of TRPM2 and voltage-gated calcium channels. J Membr Biol 247:451–459CrossRefPubMed
go back to reference Andreasson A, Arborelius L, Erlanson-Albertsson C, Lekander M (2007) A putative role for cytokines in the impaired appetite in depression. Brain Behav Immun 21:147–152CrossRefPubMed Andreasson A, Arborelius L, Erlanson-Albertsson C, Lekander M (2007) A putative role for cytokines in the impaired appetite in depression. Brain Behav Immun 21:147–152CrossRefPubMed
go back to reference Aygün H, Aydın D, İnanır S, Ekici F, Ayyıldız M, Ağar E (2015) The effects of agomelatine and melatonin on ECoG activity of absence epilepsy model in WAG/Rij rats. Turk J Biol 39:904–910CrossRef Aygün H, Aydın D, İnanır S, Ekici F, Ayyıldız M, Ağar E (2015) The effects of agomelatine and melatonin on ECoG activity of absence epilepsy model in WAG/Rij rats. Turk J Biol 39:904–910CrossRef
go back to reference Bakunina N, Pariante CM, Zunszain PA (2015) Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology 144:365–373PubMedCentral Bakunina N, Pariante CM, Zunszain PA (2015) Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology 144:365–373PubMedCentral
go back to reference Balaban H, Nazıroğlu M, Demirci K (2016) The protective role of selenium on scopolamine-induced memory impairment, oxidative stress, and apoptosis in aged rats: The involvement of TRPM2 and TRPV1 channels. doi:10.1007/s12035-016-9835-0 Balaban H, Nazıroğlu M, Demirci K (2016) The protective role of selenium on scopolamine-induced memory impairment, oxidative stress, and apoptosis in aged rats: The involvement of TRPM2 and TRPV1 channels. doi:10.1007/s12035-016-9835-0
go back to reference Cyranowski JM, Marsland AL, Bromberger JT, Whiteside TL, Chang Y, Matthews KA (2007) Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro. Brain Behav Immun 21:229–237CrossRefPubMed Cyranowski JM, Marsland AL, Bromberger JT, Whiteside TL, Chang Y, Matthews KA (2007) Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro. Brain Behav Immun 21:229–237CrossRefPubMed
go back to reference Dagyte D, Crescente I, Postema F, Seguin L, Gabriel C, Mocaer E, Den Boer JA, Jaap Koolhaas JM (2011) Agomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress. Behav Brain Res 218:121–128CrossRefPubMed Dagyte D, Crescente I, Postema F, Seguin L, Gabriel C, Mocaer E, Den Boer JA, Jaap Koolhaas JM (2011) Agomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress. Behav Brain Res 218:121–128CrossRefPubMed
go back to reference de Mello AH, da Rosa SL, Moreira Cereja AC, de Bona SR, Florentino D, Modolon Martins M, Petronilho F, Quevedo J, Tezza Rezin G (2015) Effect of subchronic administration of agomelatine on brain energy metabolism and oxidative stress parameters in rats. Psychiatry Clin Neurosci. doi:10.1111/pcn.12371 PubMed de Mello AH, da Rosa SL, Moreira Cereja AC, de Bona SR, Florentino D, Modolon Martins M, Petronilho F, Quevedo J, Tezza Rezin G (2015) Effect of subchronic administration of agomelatine on brain energy metabolism and oxidative stress parameters in rats. Psychiatry Clin Neurosci. doi:10.​1111/​pcn.​12371 PubMed
go back to reference Demyttenaere K (2011) Agomelatine: a narrative review. Eur Neuropsychopharmacol 21: S703–S709. Demyttenaere K (2011) Agomelatine: a narrative review. Eur Neuropsychopharmacol 21: S703–S709.
go back to reference Ekmekcioglu C. (2006) Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother 60:97–108. Ekmekcioglu C. (2006) Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother 60:97–108.
go back to reference Eren I, Nazıroğlu M, Demirdaş A (2007a) Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res 32:1188–1195CrossRefPubMed Eren I, Nazıroğlu M, Demirdaş A (2007a) Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res 32:1188–1195CrossRefPubMed
go back to reference Eren I, Naziroğlu M, Demirdaş A, Celik O, Uğuz AC, Altunbaşak A, Ozmen I, Uz E (2007b) Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochem Res 32:497–505CrossRefPubMed Eren I, Naziroğlu M, Demirdaş A, Celik O, Uğuz AC, Altunbaşak A, Ozmen I, Uz E (2007b) Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochem Res 32:497–505CrossRefPubMed
go back to reference Espino J, Bejarano I, Paredes SD, Barriga C, Rodríguez AB, Pariente JA (2011) Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions. J Pineal Res 51:195–206CrossRefPubMed Espino J, Bejarano I, Paredes SD, Barriga C, Rodríguez AB, Pariente JA (2011) Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions. J Pineal Res 51:195–206CrossRefPubMed
go back to reference Freiesleben SD, Furczyk K (2015) A systematic review of agomelatine-induced liver injury. J Mol Psych 3:4CrossRef Freiesleben SD, Furczyk K (2015) A systematic review of agomelatine-induced liver injury. J Mol Psych 3:4CrossRef
go back to reference Gupta S, Sharma B (2014) Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington’s disease. Pharmacol Biochem Behav 122:122–135CrossRefPubMed Gupta S, Sharma B (2014) Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington’s disease. Pharmacol Biochem Behav 122:122–135CrossRefPubMed
go back to reference Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658CrossRefPubMed Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658CrossRefPubMed
go back to reference Inanir S, Copoglu US, Kokacya H, Dokuyucu R, Erbas O, Inanır A (2015) Agomelatine protection in an LPS-induced psychosis-relevant behavior model. Med Sci Monit 21:3834–3839CrossRefPubMedPubMedCentral Inanir S, Copoglu US, Kokacya H, Dokuyucu R, Erbas O, Inanır A (2015) Agomelatine protection in an LPS-induced psychosis-relevant behavior model. Med Sci Monit 21:3834–3839CrossRefPubMedPubMedCentral
go back to reference Kahya MC, Naziroğlu M, Çiğ B. (2015) Melatonin and selenium reduce plasma cytokine and brain oxidative stress levels in diabetic rats. Brain Inj 29:1490–1406. Kahya MC, Naziroğlu M, Çiğ B. (2015) Melatonin and selenium reduce plasma cytokine and brain oxidative stress levels in diabetic rats. Brain Inj 29:1490–1406.
go back to reference Karakus E, Halici Z, Albayrak A, Polat B, Bayir Y, Kiki I, Cadirci E, Topcu A, Aksak S (2013) Agomelatine: An antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats. Hum Exp Toxicol 32:846–857CrossRefPubMed Karakus E, Halici Z, Albayrak A, Polat B, Bayir Y, Kiki I, Cadirci E, Topcu A, Aksak S (2013) Agomelatine: An antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats. Hum Exp Toxicol 32:846–857CrossRefPubMed
go back to reference Kharwar RK, Haldar C (2012) Daily variation in antioxidant enzymes and lipid peroxidation in lungs of a tropical bird Perdicula asiatica: role of melatonin and nuclear receptor RORα. Comp Biochem Physiol A Mol Integr Physiol 162:296–302CrossRefPubMed Kharwar RK, Haldar C (2012) Daily variation in antioxidant enzymes and lipid peroxidation in lungs of a tropical bird Perdicula asiatica: role of melatonin and nuclear receptor RORα. Comp Biochem Physiol A Mol Integr Physiol 162:296–302CrossRefPubMed
go back to reference Kumar H, Sharma BM, Sharma B (2015) Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder. Neurochem Int 91:34–45CrossRefPubMed Kumar H, Sharma BM, Sharma B (2015) Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder. Neurochem Int 91:34–45CrossRefPubMed
go back to reference Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958CrossRefPubMed Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958CrossRefPubMed
go back to reference Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin- Phenol reagent. J Biol Chem 193:265–275PubMed Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin- Phenol reagent. J Biol Chem 193:265–275PubMed
go back to reference Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D (2003) The novel melatonin agonist Agomelatine (S20098) Is anantagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 306:954–964CrossRefPubMed Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D (2003) The novel melatonin agonist Agomelatine (S20098) Is anantagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 306:954–964CrossRefPubMed
go back to reference Nazıroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001CrossRefPubMed Nazıroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001CrossRefPubMed
go back to reference Nazıroğlu M (2009) Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res 34:2181–2191CrossRefPubMed Nazıroğlu M (2009) Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res 34:2181–2191CrossRefPubMed
go back to reference Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Greshenfeld HK, et al. (2002) Preclinical models: status of basic research in depression. Biol Psychiatry 52:503–528CrossRefPubMed Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Greshenfeld HK, et al. (2002) Preclinical models: status of basic research in depression. Biol Psychiatry 52:503–528CrossRefPubMed
go back to reference Nicholson TE, Renton KW (2001) Role of cytokines in the lipopolysaccharide-evoked depression of cytochrome P450 in the brain and liver. Biochem Pharmacol 62:1709–1717CrossRefPubMed Nicholson TE, Renton KW (2001) Role of cytokines in the lipopolysaccharide-evoked depression of cytochrome P450 in the brain and liver. Biochem Pharmacol 62:1709–1717CrossRefPubMed
go back to reference Placer ZA, Cushman L, Johnson BC (1966) Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359–364CrossRefPubMed Placer ZA, Cushman L, Johnson BC (1966) Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359–364CrossRefPubMed
go back to reference Sedlak J, Lindsay RHC (1968) Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann’ s reagent. Anal Biochem 25:192–205CrossRefPubMed Sedlak J, Lindsay RHC (1968) Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann’ s reagent. Anal Biochem 25:192–205CrossRefPubMed
go back to reference Senol N, Nazıroğlu M, Yürüker V (2014) N-acetylcysteine and selenium modulate oxidative stress, antioxidant vitamin and cytokine values in traumatic brain injury-induced rats. Neurochem Res 39:685–692CrossRefPubMed Senol N, Nazıroğlu M, Yürüker V (2014) N-acetylcysteine and selenium modulate oxidative stress, antioxidant vitamin and cytokine values in traumatic brain injury-induced rats. Neurochem Res 39:685–692CrossRefPubMed
go back to reference Shirazi A, Mihandoost E, Ghobadi G, Mohseni M, Ghazi-Khansari M (2013) Evaluation of radioprotective effect of melatonin onwhole body irradiation induced liver tissue damage. Cell J 14:292–297PubMedPubMedCentral Shirazi A, Mihandoost E, Ghobadi G, Mohseni M, Ghazi-Khansari M (2013) Evaluation of radioprotective effect of melatonin onwhole body irradiation induced liver tissue damage. Cell J 14:292–297PubMedPubMedCentral
go back to reference Sierra-Honigmann MR, Murphy PA (1992) Suppression of interleukin–1 action by phospholipase-A2 inhibitors in helper T lymphocytes. Pept Res 5:258–261PubMed Sierra-Honigmann MR, Murphy PA (1992) Suppression of interleukin–1 action by phospholipase-A2 inhibitors in helper T lymphocytes. Pept Res 5:258–261PubMed
go back to reference Suzuki J, Katoh N (1990) A simple and cheap method for measuring vitamin A in cattle using only a spectrophotometer. Jpn J Vet Sci 52:1282–1284 Suzuki J, Katoh N (1990) A simple and cheap method for measuring vitamin A in cattle using only a spectrophotometer. Jpn J Vet Sci 52:1282–1284
go back to reference Tardito D, Molteni R, Popoli M, Racagni G (2012) Synergisticmechanisms involved in the antidepressant effects of agomelatine. Eur Neuropsychopharmacol 22:S482–S486CrossRefPubMed Tardito D, Molteni R, Popoli M, Racagni G (2012) Synergisticmechanisms involved in the antidepressant effects of agomelatine. Eur Neuropsychopharmacol 22:S482–S486CrossRefPubMed
go back to reference Vaváková M, Ďuračková Z, Trebatická J (2015) Markers of oxidative stress and neuroprogression in depression disorder. Oxidative Med Cell Longev 12:898393 Vaváková M, Ďuračková Z, Trebatická J (2015) Markers of oxidative stress and neuroprogression in depression disorder. Oxidative Med Cell Longev 12:898393
go back to reference Voican CS, Corruble E, Naveau S, Perlemuter G (2014) Antidepressant-induced liver injury: a review for clinicians. Am J Psychiatry 171:404–415CrossRefPubMed Voican CS, Corruble E, Naveau S, Perlemuter G (2014) Antidepressant-induced liver injury: a review for clinicians. Am J Psychiatry 171:404–415CrossRefPubMed
go back to reference Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134:319–329. Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134:319–329.
Metadata
Title
Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression
Authors
Arif Demirdaş
Mustafa Nazıroğlu
Gülin Özdamar Ünal
Publication date
01-12-2016
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 6/2016
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-016-9874-2

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