Moreover, chronic treatment with a low dose of metformin (100 mg/kg) exerts significant cardioprotection effect against HF of rat by activating the AMPK/eNOS pathway, as well as reducing circulating and myocardial levels of insulin, transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF), and tumor necrosis factor α (TNFα) [75]. This evidence concerns the gene TNF and hydrops fetalis.