Alpha-lipoic acid treatment improves adverse cardiac remodelling in the diabetic heart – The role of cardiac hydrogen sulfide-synthesizing enzymes

• Published in: Biochemical pharmacology 2022-09, Vol.203, p.115179-115179, Article 115179
• Main Authors: Dugbartey, George J., Wonje, Quinsker L., Alornyo, Karl K., Adams, Ismaila, Diaba, Deborah E.
• Format: Article
• Language: English
• Subjects: Alpha-lipoic acid (ALA); Diabetic cardiomyopathy (DCM); H2S-synthesizing enzymes; Hydrogen sulfide (H2S); Type 2 diabetes mellitus (T2DM)
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2022.115179

[Display omitted] Alpha-lipoic acid (ALA) is a licensed drug for the treatment of diabetic neuropathy. We recently reported that it also improves diabetic cardiomyopathy (DCM) in type 2 diabetes mellitus (T2DM). In this study, we present evidence supporting our hypothesis that the cardioprotective effect of ALA is via upregulation of cardiac hydrogen sulfide (H2S)-synthesizing enzymes. Following 12 h of overnight fasting, T2DM was induced in 23 out of 30 male Sprague-Dawley rats by intraperitoneal administration of nicotinamide (110 mg/kg) followed by streptozotocin (55 mg/kg) while the rest served as healthy control (HC). T2DM rats then received either oral administration of ALA (60 mg/kg/day; n = 7) or 40 mg/kg/day DL-propargylglycine (PAG, an endogenous H2S inhibitor; n = 7) intraperitoneally for 6 weeks after which all rats were sacrificed and samples collected for analysis. Untreated T2DM rats served as diabetic control (DCM; n = 9). T2DM resulted in weight loss, islet destruction, reduced pancreatic β-cell function and hyperglycemia. Histologically, DCM rats showed significant myocardial damage evidenced by myocardial degeneration, cardiomyocyte vacuolation and apoptosis, cardiac fibrosis and inflammation, which positively correlated with elevated levels of cardiac damage markers compared to HC rats (p