Sodium hydrosulphide restores tumour necrosis factor-α-induced mitochondrial dysfunction and metabolic dysregulation in HL-1 cells.

Tumour necrosis factor (TNF)-α induces cardiac metabolic disorder and mitochondrial dysfunction. Hydrogen sulphide (H₂ S) contains anti-inflammatory and biological effects in cardiomyocytes. This study investigated whether H₂ S modulates TNF-α-dysregulated mitochondrial function and metabolism in cardiomyocytes. HL-1 cells were incubated with TNF-α (25 ng/mL) with or without sodium hydrosulphide (NaHS, 0.1 mmol/L) for 24 hours. Cardiac peroxisome proliferator-activated receptor (PPAR) isoforms, pro-inflammatory cytokines, receptor for advanced glycation end products (RAGE) and fatty acid metabolism were evaluated through Western blotting. The mitochondrial oxygen consumption rate and adenosine triphosphate (ATP) production were investigated using Seahorse XF24 extracellular flux analyzer and bioluminescence assay. Fluorescence intensity using 2', 7'-dichlorodihydrofluorescein diacetate was used to evaluate mitochondrial oxidative stress. NaHS attenuated the impaired basal and maximal respiration, ATP production and ATP synthesis and enhanced mitochondrial oxidative stress in TNF-α-treated HL-1 cells. TNF-α-treated HL-1 cells exhibited lower expression of PPAR-α, PPAR-δ, phosphorylated 5' adenosine monophosphate-activated protein kinase-α2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase-1, PPAR-γ coactivator 1-α and diacylglycerol acyltransferase 1 protein, but higher expression of PPAR-γ, interleukin-6 and RAGE protein than control or combined NaHS and TNF-α-treated HL-1 cells. NaHS modulates the effects of TNF-α on mitochondria and the cardiometabolic system, suggesting its therapeutic potential for inflammation-induced cardiac dysfunction.