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.

Casticin induces apoptosis and G0/G1 cell cycle arrest in gallbladder cancer cells

“…AKT is a key downstream effector of PI3K and is down-regulated in various cancers, including osteosarcoma and prostate cancer [31]. Previous studies have demonstrated that Akt inactivation might inhibit the expression of proteins associated with events that mediate the cancer development and progression, including apoptosis and cell cycle progression [29, 32, 33]. In our study, the results of the western blot analysis demonstrated that casticin significantly decreased p-Akt expression and that this effect was accompanied by an increase in p27.…”

Molecular mechanisms of trauma-induced acute kidney injury: Inflammatory and metabolic insights from animal models

“…More recently, several studies have examined this p38 pathway even further while simultaneously elucidating additional molecular mechanisms. For example, Guo et al showed that serum creatinine levels tripled after 40%TBSA scald injury in rats, which was reduced with the anti-oxidant astaxanthin [110]. This anti-oxidant partially blocked lipid peroxidation (MDA) and restored levels of SOD and catalase, while preventing apoptosis.…”

Research Progress of Astaxanthin on Contrast agent induced acute kidney injury

“…effect 34,35 . Studies have shown that the protective effects of astaxanthin against many kidney diseases is related to antiapoptosis 3,4,36 . Considering the crucial role of oxidative stress in inducing pathological changes of IR and the antioxidant properties of ATX, ATX might alleviate tubular necrosis/ apoptosis and inflammation via scavenging free radical 19 .…”

“…Many studies have proven that astaxanthin has a preventive effect on various kidney diseases [1][2][3][4][5] . Oxidative stress and apoptosis are common pathophysiological features of contrast agent induced acute kidney injury (CI-AKI), hence ATX may have a potential therapeutic role in this condition.…”