title: L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats.
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.
authors.affiliation: Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu, India.
authors.forename: Tharmarajan
authors.initials: T
authors.lastname: Ramprasath
authors.forename: Palani Hamenth
authors.initials: PH
authors.lastname: Kumar
authors.forename: Shanavas Syed Mohamed
authors.initials: SS
authors.lastname: Puhari
authors.forename: Ponniah Senthil
authors.initials: PS
authors.lastname: Murugan
authors.forename: Varadaraj
authors.initials: V
authors.lastname: Vasudevan
authors.forename: Govindan Sadasivam
authors.initials: GS
authors.lastname: Selvam
mesh_terms: D000818:Animals; D051381:Rats; D000496:Alloxan / Q000494:pharmacology; D001120:Arginine / Q000008:administration & dosage; D053148:Caspase 3 / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D017208:Rats, Wistar; D015854:Up-Regulation; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: D000496:Alloxan; D001120:Arginine; D053148:Caspase 3; D016328:NF-kappa B; D019331:NG-Nitroarginine Methyl Ester; D051057:Proto-Oncogene Proteins c-akt; D051267:NF-E2-Related Factor 2