Beneficial Effect Of Astaxanthin On Early Acute Kidney Injury In Severely-burned Rats

ObjectiveIn the early stage after severe burn injury,burn patients usually have to face a high risk of multiple organ injuries,and kidney is one of the most easily-damaged organs.The incidence of early acute kidney injury(AKI)in severe burn adults is high and closely related to prognosis.Therefore,it is of great significance to make an early diagnosis and a timely intervention for improving the prognosis and reducing the mortality of severe burn patients.Utilizing a classical rat burn model,this study intended to explore the details of the development of acute kidney injury after burn injury and the corresponding mechanism,to find the best time window for intervention.It also tried to evaluate the value of astaxanthin(ATX)as a potential intervention application,and to explore detailed mechanisms.MethodsIn this study,classic severe burn rat model was built by hot water bath according to previous report,which tried to mimic the physiological condition after burn injury.And we observed and evaluated the progression of the development of burn-induced acute kidney injury and the time-related changes of potential injury mechanism,such as oxidative stress,apoptosis,local inflammation,with involvement of histological assessment,blood test,immunohistochemistry staining,qRT-PCR,western blot,etc..In addition,in the present study,with the help of histological and molecular biological methods,we explored and made clear the protective effect of ATX(with low,mediun and high dosage)on early acute kidney injury following severe burn,as well as related details of regulation.Furthermore,the signaling mechanism involved in ATX effect was also investigated in this study,with information from previous studies and our prior research.ResultsIn this study,we observed a time-related elevation of tubular damage score in rat’s kidney after burn injury,accompanying with similar increase of serum creatinine(Cr)and NGAL levels,all of which indicated the development of AKI.Oxidative stress,apoptosis and local inflammation involved in the development of early AKI post burn,and varied with time going.The changes in histological structure,function and injury mechanism were more obvious at 48 h post burn,which might be the best time-window for research and treatment.ATX administration could dose-relatively and significantly lower the elevation of tubular damage score,serum Cr and NGAL levels was lowered.Besides,ATX could also attenuate the increase of oxidation-reduction potential(ORP)and MDA,and recover decreased activity of endogenous antioxidant enzyme---superoxide dismutase(SOD)and catalase(CAT).Meanwhile,ATX application could ameliorate the renal apoptosis and down-regulate the phosphorylation or expression of signaling proteins involved in mitochondrial apoptotic pathway(Akt/Bad/Cytochrome C/cleaved caspase 9/3).The burn induced aggregation of MPO,IL-1β,IL-6 could be decreased by ATX,as well as the expression of TLR4 and phosphorylation of downstream IKK、IκB、NF-κB.Conclusions(1)In the early stage post burn(within 3 d),the renal tissue of severely-burned rats showed obvious histological injury,as well as functional deterioration,both of which indicated the occurrence of acute kidney injury.And this progression was related to the development of increased oxidative stress,cell apoptosis and local inflammation secondary to burn insults.(2)ATX administration could significantly attenuate histological injury and functional deterioration in severely-burned rats,and this dose-related protective effect could be attributed to its ability to ameliorate burn induced oxidative stress elevation,aggravated cell apoptosis and tissue inflammation.(3)The protective effect of ATX may be based on its regulation on mitochondrial-related apoptosis signaling and inflammation-related TLR4/NF-κB pathway.