Gallic acid attenuates cadmium mediated cardiac hypertrophic remodelling through upregulation of Nrf2 and PECAM-1signalling in rats

[Display omitted] •Cd disrupts structural integrity of heart leading to cardiac hypertrophic remodelling.•Cd elevates cardiac marker enzymes and lipid levels in blood.•GA enhances antioxidant activity & decreases the expression of hypertrophy markers.•GA inhibits Cd mediated hypertrophy by regulating Nrf2 and PECAM-1 signalling pathway. Gallic acid (GA) is an abundant natural polyphenolic compound found in vegetable and fruits that reduces the cardiac disease risk factor. This study aims to evaluate GA's role on cadmium (Cd) induced cardiac remodelling in experimental rats. Male Wistar rats were exposed to Cd (15 ppm) in drinking water and administered with GA orally (15 mg/kg/d) for 60 days. The results showed that GA regulated the lipid profile and reduced the LDL to 57 % compared with Cd treated rats. GA inhibited cardiac marker enzymes activity of CK-NAC (to 72.7 %) and CK-MB (to 100.3 %). Moreover, GA attenuated lipid peroxidation and enhanced the cardiac glutathione S transferase (GST) activity (89.2 %), glutathione peroxidase (GPx) (87 %), superoxide dismutase (SOD) (88.4 %) and catalase (CAT) activity (86.5 %). Histopathological examination showed that GA impaired the ventricular hypertrophy and fibrotic proliferation induced by Cd in rats. The combination of GA + Cd, decreased the gene expression of ANP (1-fold), BNP (0.5-fold) and β- MHC (0.9-fold). Furthermore, GA significantly reduced the expression of profibrotic (TGF-β) and proinflammatory (MCP-1) gene in Cd intoxicated rats. GA upregulated the expression of Nrf2 (2-fold), HO-1 (3-fold), and PECAM-1 (0.6-fold), which augments the detoxifying enzyme activity and cellular immunity in Cd intoxicated rats. The increased protein expression of Nrf2, PECAM-1 and decreased AKT-1 levels confirmed the mechanical action of GA during the hypertrophic condition. Thus, our results suggest that GA could act as a potential therapeutic agent regulating Nrf2 and PECAM-1 signalling pathways, thereby ameliorating Cd-induced pathological cardiac remodelling.