title: Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression.
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.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Arif
authors.initials: A
authors.lastname: Demirdaş
authors.affiliation: Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Gülin Özdamar
authors.initials: GÖ
authors.lastname: Ünal
mesh_terms: D000081:Acetamides / Q000009:adverse effects* / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000097:blood* / Q000209:etiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood* / Q000150:complications; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D016207:Cytokines; C084711:agomelatine; D009281:Naphthalenes
keywords: Brain; Cytokine; Depression; Glutathione; Liver; Oxidative stress