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  • Title: 2,5-Dihydroxyacetophenone attenuates acute kidney injury induced by intra-abdominal infection in rats.
    Author: Han T, Jiang Y, Ge W, Lu Y, Liu R, Sun Z.
    Journal: Nephrology (Carlton); 2024 Oct; 29(10):636-644. PubMed ID: 39054771.
    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.
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