Itaconic Acid and Its Isomers Ameliorate Renal Ischemia-Reperfusion Injury in Rats by Inhibiting NLRP3-Mediated Inflammation.

BACKGROUND: Itaconic acid and its isomers citraconic acid and mesaconic acid are a recently identified class of metabolites with anti-inflammatory and antioxidant effects. This study investigates their roles in ischemia-reperfusion-induced acute kidney injury. METHODS: In this study, a rat model of renal ischemia-reperfusion injury (IRI) was established, and itaconic acid, citraconic acid and mesaconic acid were administered as a preoperative intervention. After the operation, renal injury was evaluated by contrast-enhanced ultrasound, biochemical analyses and histopathological staining. RESULTS: The intervention with itaconic acid and its isomers reduced the production of the inflammatory cytokines interleukin-18 (IL-18) (p < 0.05), inhibited activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome (p < 0.05), and reduced reactive oxygen species levels (p < 0.05). The intervention with itaconic acid and mesaconic acid reduced the production of the inflammatory cytokine interleukin-1β (IL-1β) (p < 0.05). The expression of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) spot protein in the intervention group was significantly lower than that in the renal ischemia-reperfusion injury (IRI) group (p < 0.01). CONCLUSIONS: These findings suggest that itaconic acid, citraconic acid, and mesaconic acid may be potential therapeutic agents for renal ischemia-reperfusion through their anti-inflammatory and antioxidant effects.