Abstract
Climate change has resulted in a marked increase in heat extremes that carry a severe risk for morbidity and mortality. Kidney is sensitive to heat stimulation, and acute kidney injury (AKI) is the early event. In this study, we investigated the adverse effects of heat extremes and their underlying mechanism. A total of 16 wild-type C57BL/6N mice were randomly divided into groups of control (exposed to 22 ± 0.5 °C) and heat (exposed to 39.5 ± 0.5 °C until the core body temperature reached the maximum). First, extreme heat exposure induced AKI evidenced by kidney dysfunction and morphological impairment. In addition, heat exposure suppressed expression of molecules for mitochondrial energetics and fatty acid beta-oxidation and disturbed the balance of oxidative stress in the kidney. Moreover, heat exposure enhanced the protein levels in the upstream signaling pathway for NLRP3 inflammasome formation, followed by NLRP3 inflammasome activation and inflammatory cytokine production. These findings demonstrated that acute extreme heat exposure may induce AKI through the NLRP3 inflammasome formation and activation.