Dapagliflozin Guards Against Cadmium-Induced Cardiotoxicity via Modulation of IL6/STAT3 and TLR2/TNF[alpha] Signaling Pathways

Cadmium (Cd) is a common environmental pollutant that leads to severe cardiotoxic hazards. Several studies were carried out to protect the myocardium against Cd-induced cardiotoxicity. Up till now, no researches evaluated the protective effect of dapagliflozin (DAP) against Cd induced cardiotoxicity. Thus, we aimed to explore the role of DAP in such model with deep studying of the involved mechanisms. 40 male Wistar albino rats were included in current study. Cd (5 mg/kg/day) was administered orally for 7 days to induce cardiotoxicity with or without co-administration of DAP in three different doses (2.5, 5, 10 mg/kg/day) orally for 7 days. Our data revealed that Cd could induce cardiotoxicity with significant increase in serum cardiac enzymes, heart weight, tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF[alpha]), nuclear factor kappa B (NF[kappa]B), toll like receptor2 (TLR2), interleukin 6 (IL6) and caspase3 immunoexpression with abnormal histopathological changes. In addition, Cd significantly decreased the level of heme oxygenase1 (HO1), nuclear factor erythroid 2-related factor 2 (Nrf2), signal transducer and activator of transcription (STAT3), reduced glutathione (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC). Co-administration of DAP could ameliorate Cd cardiotoxicity with significant improvement of the biochemical and histopathological changes. We found that DAP had protective properties against Cd induced cardiotoxicity and this may be due to its anti-oxidant, anti-inflammatory, anti-apoptotic properties and modulation of IL6/STAT3 and TLR2/TNF[alpha]-signaling pathways.