2,5‐Dihydroxyacetophenone attenuates acute kidney injury induced by intra‐abdominal infection in rats

Abstract Aims As one of the most serious complications of sepsis, acute kidney injury (AKI) is pathologically associated with excessive inflammation. 2,5‐Dihydroxyacetophenone (DHAP) is isolated from Radix rehmanniae praeparata and exhibit potent anti‐inflammatory property. This research aimed at determining the role of DHAP in sepsis‐associated AKI (SA‐AKI) and the underlying mechanism. Methods Plasma creatinine (Cre), blood urea nitrogen (BUN), tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels of SA‐AKI patients were detected to evaluate their clinical characteristics. SA‐AKI rat models were established by using caecum ligation puncture (CLP) surgery. CLP‐induced rats were administered via oral gavage with 20 or 40 mg DHAP after 2 h of CLP surgery. Subsequently, survival rates, serum indexes, histopathological changes, inflammatory factors, renal function indexes and extracellular regulated protein kinases (ERK) and nuclear factor‐κB (NF‐κB) signalling pathways were detected. Results SA‐AKI patients exhibited markedly higher levels of plasma Cre, BUN, TNF‐α and IL‐1β than healthy people. Compared with sham rats, CLP‐induced septic rats showed significantly decreased survival rate, increased serum lactate dehydrogenase activity and serum lactate level, obvious renal histopathological injury, upregulated TNF‐α, IL‐1β and TGF‐β1 levels, elevated serum creatinine, BUN and serum cystatin C concentrations, serum neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1 levels and reduced renal artery blood flow. All the above CLP‐induced changes in septic rats were mitigated after DHAP administration. Additionally, CLP‐induced elevation in phosphorylated‐ERK1/2 and nuclear NF‐κB p65 protein levels was inhibited by DHAP treatment. Conclusion DHAP hinders SA‐AKI progression in rat models by inhibiting ERK and NF‐κB signalling pathways. image