Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organisms that exerts many biological effects in trauma and disease. ATX is also suggested to have anti-inflammatory activity. Hence, we attempted to explore the role of ATX in protecting against early postburn AKI via its anti-inflammatory effects and the related mechanisms. A severely burned model was established for histological and biochemical assessments based on adult male rats. We found that oxidative stress-induced tissue inflammation participated in the development of early AKI after burn injury and that the MyD88-dependent TLR4/NF-κB pathway was activated to regulate renal inflammation. The TLR4 and NF-κB inhibitors TAK242 and PDTC showed similar effects in attenuating burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in the kidneys was downregulated, while the TLR4/MyD88/NF-κB axis was inhibited in a dose-related manner. TAK242 and PDTC could enhance the anti-inflammatory effect of high-dose ATX, whereas lipopolysaccharide (LPS) reversed its action. Furthermore, the expression of heme oxygenase (HO)-1 was upregulated by ATX in a dose-related manner. Collectively, the above data suggest that ATX protects against renal inflammation in a dose-related manner by regulating the TLR4/MyD88/NF-κB axis and HO-1 and ultimately prevents early AKI following severe burns.

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Background: Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically-burned patients. Renal inflammation plays a vital role in the progression of early AKI. Astaxanthin (ATX) is a strong antioxidant widely-distributed in marine organisms, exhibiting diverse biological effects in trauma and diseases. The anti-inflammatory property of ATX is also suggested. Hence, we attempted to explore the anti-inflammation-based protection of ATX against early AKI post-burn and related mechanisms. Methods: A severely-burned rat model was established in this study. The changes of renal structure and function were determined by hematoxylin-eosin staining and blood test. The oxidative status in kidneys was detected by commercial kits and quantitative real time PCR. Furthermore, immunofluorescence staining, quantitative real‐time, and western blot were performed on renal tissues of burned rats to explore the underlying effects and mechanisms of ATX on burn-induced AKI with the help of inflammation inducer and several signal inhibitors.Results: We found oxidative stress-induced tissue inflammation participated in the development of early AKI after burn paralleling with the deterioration of histological damage and function in kidneys, and MyD88-dependent TLR4/NF-kB pathway was activated to regulate renal inflammation. TLR4 and NF-kB inhibitor-TAK242 and PDTC showed similar effects to attenuate burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in kidneys was downregulated, while TLR4/MyD88/NF-kB axis was inhibited dose-relatedly. Lipopolysaccharide (LPS) could reverse the anti-inflammatory effect of high-dose ATX, whereas TAK242 and PDTC antagonized its action. Furthermore, the expression of heme oxygenase(HO)-1 was also dose-relatedly upregulated by ATX. Conclusions: Collectively, the data above suggests ATX dose-relatedly protects against renal inflammation through regulating TLR4/MyD88/NF-kB axis and HO-1, and finally prevent early AKI following severe burns.