Curcumin alleviates dry/heat stress-induced acute kidney injury by reducing the formation of neutrophil extracellular traps in rats.

Abstract

Exposure to extreme heat is associated with acute kidney injury (AKI), and neutrophil extracellular traps (NETs) may contribute to the pathogenesis of AKI under heat stress (HS). Curcumin has demonstrated protective effects on renal function. However, the precise role of NETs and the underlying mechanism by which curcumin confers protection against HS-induced AKI remain unclear. An AKI rat model was established under dry/heat conditions for 1.5 h, followed by recovery periods of 2 h and 24 h at room temperature, respectively. Rats were pretreated with curcumin at doses of 50 or 100 mg/kg prior to HS exposure. Renal injury was assessed by measuring serum creatinine (CREA) and urea nitrogen (UREA) levels, H&E staining, and Tunel assays. Immunofluorescence and ELISA kits were used to quantify NETs levels and inflammation both in vitro and in vivo. The results confirmed that neutrophil infiltration and NETs formation correlated with kidney tissue damage following HS in a dry/heat environment. Treatment with curcumin attenuated HS-induced tubular injury, hemorrhage, and necrosis, and reduced serum UREA and CREA levels. Furthermore, renal levels of inflammatory factors including interleukin (IL)-1β and tumor necrosis factor (TNF)-α, hydrogen peroxide (HO), myeloperoxidase (MPO) and NETs were significantly decreased after curcumin treatment. In vitro experiments showed that curcumin can inhibit neutrophil activation and suppressed NETs formation by blocking reactive oxygen species (ROS) and MPO production. In summary, curcumin ameliorates dry/heat stress-induced AKI in rats by reducing NETs formation. Moreover, inhibition of NETs may represent a potential therapeutic strategy for mitigating AKI following HS.