Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro

Abstract

Acute kidney injury is a fatal disease characterized by a rapid deterioration of kidney function. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a natural product extracted from Capsicum. The aim of this study was to explore the protective effect of capsaicin on inflammation, apoptosis, and mitochondrial dysfunction in an in vitro model of acute kidney injury. Lipopolysaccharide (LPS)-induced acute kidney injury model was established in HK-2 cells to investigate the protective effect of capsaicin. Cell viability was assessed using CCK-8 assay, and protein expression was detected using western blot and immunofluorescence assay. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential were analyzed by flow cytometry. Cell apoptosis was detected by propidium iodide staining. The results showed that capsaicin ameliorated LPS-induced cytotoxicity in vitro and attenuated the release of interleukin (IL)-1β and IL-18. Intriguingly, genipin abolished the protective effect of capsaicin. Molecularly, capsaicin activated transient receptor potential cation channel subfamily V member 1 –mitochondrial uncoupling protein 2 axis and inhibited caspase-1-mediated pyroptosis. In addition, capsaicin alleviated LPS-induced ROS production and mitochondrial membrane potential disruption and inhibited apoptosis. These findings suggest that capsaicin shows a protective effect in in vitro acute kidney injury model.

Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease

“…There is accruing evidence indicating that capsaicin administration may prevent AKI onset in various models of kidney damage. In particular, in an in vitro model of AKI [48], capsaicin ameliorated cytotoxicity induced by lipopolysaccharides, reducing the release of specific interleukins (i.e., IL-1β and IL-18) and reactive oxygen species (ROS). Specifically, such an effect has been attributed to the activation of the TRPV1 channel and mitochondrial uncoupling protein-2 (TRPV1/UCP2) axis, triggering a protective effect against inflammation, pyroptosis, apoptosis, and mitochondrial dysfunction.…”