title: The Effect of Chronic Mild Stress and Imipramine on the Markers of Oxidative Stress and Antioxidant System in Rat Liver.
abstract: Liver abnormalities have been reported to occur in up to 20 % of patients on a long-term therapy with the tricyclic antidepressant drug imipramine (IMI). The mechanism involved in this IMI-induced process is unknown but a contribution of oxidative stress is highly likely. Chronic mild stress (CMS) is widely used for modeling depressive-like behavior in rats. In the present study, we examined the effects of CMS and chronic IMI treatment, applied alone or in combination, on the levels of oxidative stress markers, such as reactive oxygen species (ROS), malondialdehyde (MDA), non-protein sulfhydryl groups, and sulfane sulfur as well as on activities of key antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase in the rat liver. Administration of IMI for 5 weeks to rats subjected to CMS resulted in a gradual significant reduction of anhedonia measured by sucrose intake, in a majority of animals (CMS IMI-reactive, CMS IMI-R), although about 20 % of rats did not respond to the IMI treatment (CMS IMI non-reactive, CMS IMI-NR). CMS-induced hepatic oxidative stress, estimated by increased ROS and MDA concentrations, was not prevented by the IMI administration, moreover, in CMS IMI-NR animals, the level of the marker of lipid peroxidation, i.e., MDA was increased in comparison to CMS-subjected rats and activity of antioxidant enzymes (GPx and CAT) was decreased compared to IMI-treated rats. The clinical significance of this observation remains to be established.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Duda
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Curzytek
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland. kubera@if-pan.krakow.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
authors.affiliation: Institute of Medical Biochemistry, Jagiellonian University, Medical College, 7 Kopernika Street, 31-034, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Iciek
authors.affiliation: Institute of Medical Biochemistry, Jagiellonian University, Medical College, 7 Kopernika Street, 31-034, Kraków, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Kowalczyk-Pachel
authors.affiliation: Institute of Medical Biochemistry, Jagiellonian University, Medical College, 7 Kopernika Street, 31-034, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bilska-Wilkosz
authors.affiliation: Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Lorenc-Koci
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Leśkiewicz
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Regulska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ślusarczyk
authors.affiliation: Behavioral Pharmacology Laboratory, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gruca
authors.affiliation: Behavioral Pharmacology Laboratory, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Władysław
authors.initials: W
authors.lastname: Lasoń
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
mesh_terms: D000704:Analysis of Variance; D059445:Anhedonia / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000975:Antioxidants; D019422:Dietary Sucrose; D007099:Imipramine
keywords: Chronic mild stress; Depression; Imipramine; Liver; Oxidative stress