Myocardial complications induced by hypothyroidism in rats: effects of metformin and alpha lipoic acid

Hypothyroidism has adverse effects on heart metabolism and functions including reduced heart rate, cardiac output and cardiac contractility. The therapeutic effects of alpha lipoic acid (LA) and metformin (MET) against hypothyroidism-induced myocardial complications were assessed in the current study. Rats were divided into control, propylthiouracil (PTU)-induced hypothyroidism model, hypothyroidism model treated with LA and/or MET. Serum thyroid hormones (T3, T4 and TSH) were measured. Lipid peroxidation (MDA), nitric oxide (NO), reduced glutathione (GSH), nuclear factor erythroid 2–related factor 2 (NrF2), B-cell lymphoma 2 (BCL2), nuclear factor kappa B (NF-κB), serotonin (5-HT), norepinephrine (NE) and dopamine (DA), acetylcholinesterase (AChE), monoamine oxidase (MAO) and Na⁺,K⁺,ATPase were measured in the cardiac tissue. The histopathological changes were also assessed. PTU significantly decreased T₃ and T₄ and significantly increased TSH. A significant increase in MDA, GSH, NrF₂, BCL₂, NF-κB, 5-HT, NE, DA, AChE, MAO and Na⁺,K⁺,ATPase and a significant decrease in NO were observed in the cardiac tissue of hypothyroidism model. This was associated with histopathological changes. LA alone or with MET restored T₃ and TSH and improved almost all the biochemical changes except the decreased NO and the increased DA. MET restored T_3, T₄ and TSH and the biochemical changes induced in the cardiac tissue. MET ameliorated the histopathological changes that were still observed with LA alone or with MET. The present findings indicate that MET had cardioprotective effect against hypothyroidism and its myocardial complications. This effect was less prominent with LA alone or in combination with MET.