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

Abstract

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.

Keywords: 4-(trifluoromethyl) aniline (PubChem CID: 9964); Acetylcholine (PubChem CID: 187); Diabetes; Diabetic complications; Diethylether (PubChem CID: 3283); Ethanol (PubChem CID: 702); Glucose (PubChem CID: 79025); Gαq-RGS2 loop activator; N-(1-naphthyl)ethylenediamine (PubChem CID: 15107); Nitroglycerine (PubChem CID: 4510); Sodium citrate (PubChem CID: 6224); Streptozotocin (PubChem CID: 29327); Sulphanilamide (PubChem CID: 5333).