title: Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.
abstract: Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1β, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic inflammation, which allows the study of physio-pathological stress aspects over prolonged time periods of at least 60days.
authors.affiliation: Posgrado en Biología Experimental Biological and Health Sciences Division (DCBS), Universidad Autónoma Metropolitana Unidad Iztapalapa (UAMI), CP 09340, México, D.F., Mexico. Electronic address: anaelepl@gmail.com.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: López-López
authors.affiliation: Behavioral and Reproductive Pharmacology Laboratory, DCBS, UAMI, CP 09340, México, D.F., Mexico.
authors.forename: Herlinda Bonilla
authors.initials: HB
authors.lastname: Jaime
authors.affiliation: Pharmacology Laboratory, DCBS, UAMI, CP 09340, Mexico, D.F., Mexico.
authors.forename: María Del Carmen
authors.initials: MDC
authors.lastname: Escobar Villanueva
authors.affiliation: Posgrado en Biología Experimental Biological and Health Sciences Division (DCBS), Universidad Autónoma Metropolitana Unidad Iztapalapa (UAMI), CP 09340, México, D.F., Mexico.
authors.forename: Malinalli Brianza
authors.initials: MB
authors.lastname: Padilla
authors.affiliation: College of Science and Technology, Universidad Autónoma de la Ciudad de México-San Lorenzo Tezonco, CP 09790, México, D.F., Mexico.
authors.forename: Gonzalo Vázquez
authors.initials: GV
authors.lastname: Palacios
authors.affiliation: Pharmacology Laboratory, DCBS, UAMI, CP 09340, Mexico, D.F., Mexico. Electronic address: aaaf@xanum.uam.mx.
authors.forename: Francisco Javier Alarcón
authors.initials: FJA
authors.lastname: Aguilar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005508:Food Deprivation; D005978:Glutathione / Q000378:metabolism; D007103:Immobilization / Q000009:adverse effects; D007249:Inflammation / Q000150:complications*; D015227:Lipid Peroxidation; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014868:Water Deprivation
chemical_list: D016207:Cytokines; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D003345:Corticosterone
keywords: CUMS; Chronic stress; Inflammation; Liver; Oxidative stress; Pancreas