Regulatory mechanism of gallic acid against advanced glycation end products induced cardiac remodeling in experimental rats

• Exogenous infusion of glycated products induces cardiac fibrosis.
• In vitro prepared glycated products augments oxidative stress in the heart tissues.
• Circulating AGEs activates cardiac RAGE and NOX expression.
• Exogenous infusion of AGEs alters cardiac matrix proteins.
• Treatment using gallic acid could attenuate the AGEs mediated complications.

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 (50 mg/kg BW-intravenous injection) for 30 days. Further, GA (25 mg/kg BW) 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.