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L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2012 Nov 23; Vol. 428 (3), pp. 389-94. Date of Electronic Publication: 2012 Oct 24. - Publication Year :
- 2012
-
Abstract
- Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg(-1) body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-κB. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be used as a potential treatment method to alleviate the late diabetic complications.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Rats
Alloxan pharmacology
Caspase 3 genetics
Hyperglycemia chemically induced
Hyperglycemia drug therapy
Hyperglycemia pathology
Lipid Peroxidation drug effects
NF-kappa B genetics
NG-Nitroarginine Methyl Ester administration & dosage
Proto-Oncogene Proteins c-akt genetics
Rats, Wistar
Up-Regulation
Arginine administration & dosage
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental pathology
Gene Expression Regulation drug effects
Heart Ventricles drug effects
Heart Ventricles pathology
Oxidative Stress drug effects
NF-E2-Related Factor 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 428
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 23103544
- Full Text :
- https://doi.org/10.1016/j.bbrc.2012.10.064