A protective role of Gαq-RGS2 loop activator on streptozotocin induced diabetic complications in rats: An independent on elevated serum glucose level modulation

• Published in: European journal of pharmacology 2018-01, Vol.818, p.141-147
• Main Authors: Beladiya, Jayesh V., Chaudagar, Kiranj Kishor, Mehta, Anita A.
• Format: Article
• Language: English
• Subjects: Diabetes; Diabetic complications; Gαq-RGS2 loop activator
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2017.10.046

An overactivation of Gαq dependent signaling pathway is crucial for development of metabolic and vascular abnormalities in diabetes. Therefore, our objective was to study effects of Gαq-RGS2 loop activator (1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one) on STZ induced diabetic complications in rats. Animals were divided into four groups; normal rats, diabetic rats (Streptozotocin, STZ, 60mg/kg, i.p.), Gαq-RGS2 loop activator (1mg/kg/d, i.p., 15 d, at 6 wk after citrate buffer or STZ administration, respectively) treated normal rats and diabetic rats. At the end of 8 wk, the metabolic parameters, hemodynamic parameters, in-vivo vascular reactivity and aortic anti-oxidant status were evaluated. A treatment of Gαq-RGS2 loop activator significantly decreased serum cholesterol (P < 0.001), triglyceride (P < 0.01), systolic/diastolic/mean arterial blood pressure (P < 0.001), lactate dehydrogenase (P < 0.001), cardiac selective creatinine kinase (P < 0.001), urea (P < 0.05), creatinine (P < 0.001), aortic superoxide dismutase (P < 0.05) and catalase(P < 0.05) in diabetic rats whereas increased basal (P < 0.05) and stimulated (acetylcholine (P < 0.01) and nitroglycerine (P < 0.05)) serum nitric oxide level without affecting elevated serum glucose level. The nitroglycerin stimulated NO production was significantly (P < 0.01) increased by Gαq-RGS2 loop activator administration in normal rats, too. Collectively, Gαq-RGS2 loop activator protects rats against streptozotocin induce hemodynamic and metabolic modulation without affecting elevated serum glucose level.