The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice.

Abstract

AIM:

To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.

METHODS:

Db/db mice (n = 40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.

RESULTS:

Valsartan or LAF237 pretreatment significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase subunits also significantly decreased resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5 ± 0.7, P < 0.05; LAF237: 10.2 ± 1.7, P < 0.05), VCAM-1 (fold change: valsartan : 5.2 ± 1.2, P < 0.05; LAF237: 4.8 ± 0.6, P < 0.05), and MCP-1 (fold change: valsartan: 3.2 ± 0.6, LAF237: 4.7 ± 0.8; P < 0.05) expression. Moreover, the combination treatment with valsartan and LAF237 resulted in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction was also higher than monotherapy with valsartan or LAF237.

CONCLUSION:

These data indicated that combination treatment with LAF237 and valsartan acts in a synergistic manner on vascular oxidative stress and inflammation in type 2 diabetic mice.

• Authors: Min Shen, Dongdong Sun, Weijie Li, Bing Liu, Shenxu Wang, Zheng Zhang, Feng Cao
• Journal: Experimental diabetes research (Exp Diabetes Res) Vol. 2012 Pg. 146194 ( 2012) ISSN: 1687-5303 [Electronic] United States
• PMID: 22474415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(((3-hydroxy-1-adamantyl)amino)acetyl)-2-cyanopyrrolidine
• Angiotensin II Type 1 Receptor Blockers
• Blood Glucose
• Glp1r protein, mouse
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Pyrrolidines
• Receptors, Glucagon
• Tetrazoles
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Valsartan
• Glucagon-Like Peptide 1
• NADPH Oxidases
• Valine
• Adamantane

Topics

• Adamantane (analogs & derivatives, pharmacology)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Aorta (drug effects)
• Apoptosis (drug effects)
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (metabolism)
• Drug Synergism
• Endothelial Cells (drug effects)
• Endothelium, Vascular (drug effects)
• Glucagon-Like Peptide 1 (metabolism)
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents (pharmacology)
• Inflammation (metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Mice
• NADPH Oxidases (metabolism)
• Oxidative Stress (drug effects)
• Pyrrolidines (pharmacology)
• Receptors, Glucagon (metabolism)
• Tetrazoles (pharmacology)
• Valine (analogs & derivatives, pharmacology)
• Valsartan
• Vascular Cell Adhesion Molecule-1 (metabolism)