Hydroxycitric acid inhibits kidney stone through crystallization regulation and reduction of hyperoxalate-induced lipotoxicity

Abstract

Kidney stone is a urinary system disease with a high incidence, and effective stone drugs are limited. Hydroxycitric acid (HCA), mainly found in Garcinia cambogia and Hibiscus sabdariffa, can reduce body weight and calcium salt deposition. In this study, we explored the molecular mechanisms of HCA inhibition of renal calcium oxalate (CaOx) deposition and nephrotoxicity in an oxalate-induced cell model and rat model. HCA could effectively inhibit CaOx crystal deposition and reduce crystal adhesion and oxidative damage. Further cellular transcriptomic analysis and in vitro results showed that HCA could stably bind peroxisome proliferator-activated receptor α (PPARα), thus promoting the expression of downstream oxidative stress molecules and inhibiting calcium ion release and mitochondrial dysfunction, thus reducing oxalate-induced renal lipid peroxidation damage. HCA, a drug with the ability to modulate lipid metabolism and inhibit CaOx formation, may be a therapeutic option for the treatment of oxalate nephropathies.

Keywords

• Kidney stone
• Lipotoxicity
• Oxidative damage
• Hydroxycitric acid
• PPARα