title: Regulatory mechanism of gallic acid against advanced glycation end products induced cardiac remodeling in experimental rats.
abstract: Advanced glycation end products (AGEs) play a major role in the development of cardiovascular disorders in diabetic patients. Recent studies evidenced the beneficial role of phytochemicals in reducing the risk of cardiovascular diseases. Hence the present study was framed to investigate the protective role of Gallic acid (GA) on AGEs induced cardiac fibrosis. Rats were infused with in vitro prepared AGEs (50mg/kg BW-intravenous injection) for 30 days. Further, GA (25mg/kgBW) was administered to rats along with AGEs. On infusion of AGEs, induction of fibrotic markers, collagen deposition, oxidative marker NADPH oxidase (NOX-p47 phox subunit), AGE receptor (RAGE) and cytokines expression was evaluated in the heart tissues using RT-PCR, Western blot and immunostaining methods. AGEs infusion significantly (P<0.01) increased the HW/BW ratio and fibrosis (4-fold) with increased expression of matrix genes MMP-2 and -9 (P<0.01, respectively) in the heart tissues. Whereas, administration of GA along with AGEs infusion prevented the fibrosis induced by AGEs. Further, GA treatment effectively prevented the AGEs mediated up-regulation of pro-fibrotic genes and ECM proteins such as TNF-α, TGF-β, MMP-2 and -9 expression. In addition, the increased expression of NOX (P<0.01), RAGE (P<0.01), NF-κB (P<0.01) and ERK 1/2 on AGEs infusion were normalized by GA treatment. Thus the present study shows the protective effect of GA on the fibrotic response and cardiac remodeling process induced by advanced glycation end products from external sources.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Umadevi
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Gopi
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India. Electronic address: vellaie@gmail.com.
authors.forename: Vellaichamy
authors.initials: V
authors.lastname: Elangovan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005707:Gallic Acid / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D005707:Gallic Acid; D019255:NADPH Oxidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Advanced glycation end products; Cardiac fibrosis; Extracellular matrix; Gallic acid; NOX; RAGE