Combined diabetes and chronic stress exacerbates cytokine production and oxidative stress in rat liver and kidney

Abstract

AbstractInflammatory response and oxidative stress state have been largely described in diabetes and depression separately but not in combination. We aimed to explore the involvement of diabetes and unpredictable chronic mild stress (UCMS) separately or in combination on inflammatory response and oxidative stress. Diabetes, UCMS or combined rat models were used. Proinflammatory cytokines, Interleukin 6 (IL-6) and Tumor necrosis factor alpha (TNF-α) were assessed by real time quantitative polymerase chain reaction (q-PCR) and Enzyme-Linked Immunosorbent Assay (ELISA). Superoxide dismutase (SOD) and catalase (CAT) were determined by colorimetric assays. In the diabetes group, IL-6 mRNA expression increased by 55% and 34% (p < 0.05), respectively, in liver and kidney. UCMS alone or in combination with diabetes increased the mRNA of IL-6, respectively, by 85% and 78% in the liver and by 28% and 63% in the kidney (p < 0.01 for all). ELISA showed that diabetes and UCMS act in synergy on TNF-α and IL-6 expression. Diabetes and UCMS separately or in combination inhibited significantly (p < 0.01) the activities of the two anti-oxidant enzymes when compared to controls. The malondialdehyde (MDA) level was significantly enhanced in the group with diabetes combined with UCMS compared to UCMS alone in both organs. UCMS enhances the proinflammatory cytokines release and induces oxidative stress imbalance, and diabetes comorbidity with depression aggravates the inflammatory response and lipid peroxidation. These observations can be useful to better understand depression-induced organ damage.

Keywords

• Diabetes
• unpredictable chronic mild stress
• proinflammatory cytokine
• oxidative stress