ecdysterone and Diabetes-Mellitus--Type-1

We investigate the effects of 20-hydroxyecdysone (20E) on improving memory deficits in the current study by using an animal model of type 1 diabetes mellitus in rats. Animals in control group went on a normal diet. Rats that developed diabetes were divided into 4 groups, including STZ-induced diabetic group which was treated with saline and three 20E groups received different 20E concentrations for 12 weeks. Spatial memory performance was measured in rats by the Morris water maze. The level of nuclear factor-кB (NF-кB) in the brain was determined by real-time quantitative PCR. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were analyzed by real-time quantitative PCR and spectrophotometry. The concentrations of brain-derived neurotrophic factor (BDNF) in the brain were detected by ELISA. Compared with the control group, rats in the STZ-induced diabetic group that developed type 1 diabetes exhibited significant memory loss. In addition to the hippocampus CA1 area that displayed severe damage, significantly higher expression levels of NF-кB were observed in these rats. Furthermore, the expression levels of SOD, catalase, GSH-Px GR and BDNF were significantly decreased in rats with diabetes. By contrast, the treatment with 20E, especially at higher concentrations, reversed the above-mentioned conditions caused by diabetes. The results suggest that the 20E has a protective role in counteracting memory deficits in rats with diabetes of rat, possibly through enhancing the antioxidative ability in the brain.

Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Catalase; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Ecdysterone; Glutathione Peroxidase; Glutathione Reductase; Male; Memory Disorders; Neuroprotective Agents; NF-kappa B; Rats, Sprague-Dawley; RNA, Messenger; Streptozocin; Superoxide Dismutase

Streptozotocine (STZ) administration (5 mg/100 g) up regulates oxidative (lipid peroxidation as a marker) and nitrosative (protein nitrosilation as a marker) stresses as well as ROS (O(2-), H2O2, OH) generation in heart and aorta in rats after 60 days of STZ action. The level of oxydative stress was higher in aorta. Xanthine oxidase (XO) activation (uric acid as marker), but not lipoxygenase (LTC4 as marker) or cyclooxygenase (TxB2 as marker) are the main oxydases that generate O(2-) as calculated by correlation analysis. STZ administration led to sphingosine pools up regulation in heart and aorta, but pools of polyamines in this organ was down regulated. C27-phytosteroid hormone ecdysterone (100 ng/100 g, per os, 60 days) mimics the action of its structural analog C27-steroid hormone calcitriol (1alpha,25-dihydroxyvitamin D,) and protects rise of ROS generation (by XO inhibition), lipid peroxidation, protein nitrosilation, polyamine degradation in heart and aorta of rats after STZ administration. The new mechanism of iNOS activation, prostaglandine and tetrahydrobiopterin synthesis stimulation by ecdysterone has been proposed. It was due to stimulating enzymatic degradation of sphingosine-1-phosphate as effective regulator of iNOS, COX and GTP-cyclohydrolase in cardio-vascular system: sphingomyelin > ceramide > sphingosine > S-I-P > phosphoethanolamine > ethanolamine.

Topics: Animals; Aorta; Cardiovascular System; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Ecdysterone; Lipid Peroxidation; Male; Myocardium; Nitric Oxide; Nitrosation; Oxidative Stress; Rats; Rats, Inbred WKY; Reactive Oxygen Species