Anti-oxidative effect of vitamin D analog on incipient vascular lesion in non-obese type 2 diabetic rats.

Abstract

BACKGROUND/AIMS:

Vascular disease is one of the critical complications of diabetes. A growing body of evidence suggests that oxidative stress plays a key role for vascular disease progression. Recent studies have demonstrated a strong link between vitamin D and cardiovascular disease.

METHODS:

We investigated the anti-oxidative effects of a vitamin D analog, 22-oxacalcitriol (maxacalcitol), on vascular lesions in type 2 diabetic rats. We used Spontaneously Diabetic Torii (SDT) rats, a model of non-obese type 2 diabetes. At 20 weeks of age, SDT rats were randomly divided into three groups: diabetes mellitus (DM, n = 10), DM + maxacalcitol (DM + D, n = 10), and DM + insulin (DM + I, n = 10). The rats were sacrificed at 30 weeks for the evaluation of blood and urine samples as well as histopathology and mRNA expression in the aorta.

RESULTS:

Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells were significantly lower in the DM + I and DM + D groups than in the DM group. Real-time polymerase chain reaction analysis demonstrated that NADPH p22 phox and NADPH p47 phox mRNA levels were markedly decreased in the DM + I and DM + D groups compared with the DM group. Furthermore, the mRNA expression of MCP-1, ICAM-1 and VCAM-1 was significantly reduced in the DM + I and DM + D groups compared with the DM group.

CONCLUSION:

Our results suggest that the vasoprotective effects of vitamin D are mediated by reducing oxidative stress.

• Authors: Keiji Kono, Hideki Fujii, Kentaro Nakai, Shunsuke Goto, Riko Kitazawa, Sohei Kitazawa, Masami Shinohara, Michinori Hirata, Masafumi Fukagawa, Shinichi Nishi
• Journal: American journal of nephrology (Am J Nephrol) Vol. 37 Issue 2 Pg. 167-74 ( 2013) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 23406697 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Antioxidants
• Ccl2 protein, rat
• Chemokine CCL2
• Insulin
• Interleukin-1
• RNA, Messenger
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• 8-Hydroxy-2'-Deoxyguanosine
• C-Reactive Protein
• NADPH Oxidases
• Cyba protein, rat
• neutrophil cytosolic factor 1
• Calcitriol
• Deoxyguanosine
• maxacalcitol

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Antioxidants (pharmacology, therapeutic use)
• Aorta (metabolism, pathology)
• C-Reactive Protein (metabolism)
• Calcitriol (analogs & derivatives, pharmacology, therapeutic use)
• Chemokine CCL2 (genetics)
• Deoxyguanosine (analogs & derivatives, urine)
• Diabetes Mellitus, Type 2 (complications, drug therapy, metabolism)
• Insulin (therapeutic use)
• Intercellular Adhesion Molecule-1 (genetics)
• Interleukin-1 (blood)
• NADPH Oxidases (genetics)
• Oxidative Stress (drug effects)
• RNA, Messenger (metabolism)
• Rats
• Vascular Cell Adhesion Molecule-1 (genetics)
• Vascular Diseases (etiology)