title: Astaxanthin attenuates early acute kidney injury following severe burns in rats by ameliorating oxidative stress and mitochondrial-related apoptosis.
abstract: Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is a strong antioxidant and exhibits other biological effects that have been well studied in various traumatic injuries and diseases. Hence, we attempted to explore the potential protection of ATX against early post burn AKI and its possible mechanisms of action. The classic severe burn rat model was utilized for the histological and biochemical assessments of the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal tubular injury and the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were improved. Furthermore, relief of oxidative stress and tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX administration increased Akt and Bad phosphorylation and further down-regulated the expression of other downstream pro-apoptotic proteins (cytochrome c and caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002. Moreover, the protective effect of ATX presents a dose-dependent enhancement. The data above suggested that ATX protects against early AKI following severe burns in rats, which was attributed to its ability to ameliorate oxidative stress and inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as the Akt/Bad/Caspases signalling cascade.
authors: Department of Burns, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China. 11318225@zju.edu.cn.
authors: Song-Xue
authors: SX
authors: Guo
authors: Department of Burns, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China. zhlei288@zju.edu.cn.
authors: Han-Lei
authors: HL
authors: Zhou
authors: Department of Plastic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310000, Zhejiang, China. 21418262@zju.edu.cn.
authors: Chun-Lan
authors: CL
authors: Huang
authors: Department of Burns, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China. 2314053@zju.edu.cn.
authors: Chuan-Gang
authors: CG
authors: You
authors: Department of Plastic Surgery, Binjiang Branch, Second Affiliated Hospital, School of Medicine, Zhejiang University, 1511 Jianghong Road, Hangzhou 310000, Zhejiang, China. 21218125@zju.edu.cn.
authors: Quan
authors: Q
authors: Fang
authors: Department of Burns, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China. wuzhiqiujin@zju.edu.cn.
authors: Pan
authors: P
authors: Wu
authors: Department of Burns, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China. wangxingang8157@zju.edu.cn.
authors: Xin-Gang
authors: XG
authors: Wang
authors: Department of Burns, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China. zrssk@zju.edu.cn.
authors: Chun-Mao
authors: CM
authors: Han
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000209:Acute-Phase Proteins; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000097:blood; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D024341:Xanthophylls / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000209:Acute-Phase Proteins; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D004791:Enzyme Inhibitors; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D024341:Xanthophylls; C005948:astaxanthine; D003404:Creatinine; D058539:Phosphatidylinositol 3-Kinase