Protective effect of tretinoin derivative and TXNRD1 protein on streptozotocin induced gestational diabetes via an age-rage signaling-pathway.

Abstract

In the present study effect of tretinoin derivative was investigated on the pathogenesis of gestational diabetes mellitus (GDM) in mice model in vivo. Diabetes was induced in mice by injecting Streptozotocin (STZ) for 5consecutive days at a dose of 65 mg/kg body weight through the intraperitoneal route. Tretinoin derivative was given to the mice at 0.12 and 0.25 mg/kg doses through gavage in normal saline alternately for one week after STZ injection. The results demonstrated that tretinoin derivative administration to the diabetic mice significantly (P<0.05) alleviated the blood FBG and FINS levels. Administration of tretinoin derivative to the diabetic mice significantly (P<0.05) promoted the blood HDL level and alleviated TC and TG levels. The administration of tretinoin derivative to the diabetic mice significantly (P<0.05) alleviated the CRP, IL-6and TNF-α production in pancreatic tissues. Tretinoin derivative administration to the diabetic mice significantly (P<0.05) elevated the SOD activity, and CAT level and lowered the MDA level in pancreatic tissues. The TXNRD1 expression in diabetic mice was comparable to that in the normal group after administration of tretinoin derivativeat the dose of 0.25 mg/kg dose. In silico data demonstrated that tretinoin derivativeinteracts with TXNRD1 protein with the binding affinity ranging from -10 to 9.4 kcal/ mol. In conclusion, tretinoin derivative administration effectively regulated streptozotocin-induced changes in fasting blood glucose, insulin level, high-density lipid level and triglyceride level in diabetic mice in vivo. The streptozotocin-induced excessive production of C-reactive protein and inflammatory cytokines was also down-regulated in diabetic mice on administration of tretinoin derivative. Therefore, tretinoin derivative can be investigated further as a therapeutic agent for the treatment of gestational diabetes mellitus.