Protective Effects Of Astaxanthin On Renal Ischemia - Reperfusion Injury In Mice

Kidney transplantation presents the one of the gold standard therapies for end-stage renal diseases. Given the storage of organs from decreased donors available for transplantation, transplants using so-called “marginal” organs have increased despite their reduced viability and increased immunogenicity compared with living donor renal allografts [1, 2]. Ischemia/reperfusion(IR), an inevitable consequence of kidney transplantation, is one of the major contributors to the development of primary injury, and delayed graft function in kidney transplantation, leading to worse long-term function [3, 4].Although the mechanisms by which organ damage occurs in IR-induced renal injury are incompletely understood, it has been suggested that oxidative injury following IR most likely contributed to the pathogenesis of IR [5]. During the ischemia phase, ischemia-induced hypoxia could induce ATP depletion and hypoxanthine accumulation. After reintroduction of blood flow, reactive oxygen species(ROS) are generated [6], leading to tubular apoptosis/necrosis and local inflammation [7]. As a result of oxidative and inflammatory injury caused by IR, tubular epithelial cells might undergo profound functional alterations including losing tight junctions and epithelial-to-mesenchymal transition(EMT) [8, 9]. Previous reports have demonstrated that deficiency of anti-oxidant could exacerbate IR injury and anti-oxidants such as superoxide dismutase, catalase, or vitamin E had beneficial effects for IR injury [10, 11], supporting oxidative stress as a major contributor in the development of IR-induced injury.Astaxanthin(ATX) is a carotenoid pigment naturally existing in seafood, such as salmon, shells of crabs and shrimps, as well as a wide variety of plants and algae [12]. The United States FDA approved ATX as a feed additive for the aquaculture industry in 1987 and approved its use as a dietary supplement in 1999 [13]. The molecular structure of ATX is similar to that of β-carotene(Fig.S.1), which gives ATX anti-oxidant capacity [14]. ATX exhibits free radical scavenging activity and protect against lipid peroxidation and oxidative damage to cell membranes, cells, and tissues, suggesting ATX as a powerful biological anti-oxidant [15]. Unlike carotenoids, ATX has oxygenated groups on each ring structure(Fig.S.1), making ATX highly polar and dramatically enhancing its membrane function to protect against degenerative conditions. This makes ATX a significantly greater anti-oxidant than β-carotene [16]. Previous studies on animal models have shown protective effects of ATX in IR-induced liver [17], brain [18, 19], or cardiovascular [20] injury by reducing oxidant-induced damage. However, the protective effect of ATX against IR-induced renal injury still remains unknown.Objective:To explore the protective effects of astaxanthin(ATX) for ischemia-reperfusion induced renal injury in mice.Methods:Male ICR mice were randomly divided into 4 groups: sham group(Sham), Sham group treated with ATX(Sham + ATX), ischemia-reperfusion group(IR), ischemia-reperfusion group treated with ATX(IR+ ATX). ATX(5 mg/kg/d) or olive oil was administrated via oral gavage for 2 weeks. Renal ischemia-reperfusion injury was induced by clipping the left kidney for 50 minutes. Blood serum and kidney tissue specimens were collected 24 hours after IR procedure. Blood urea nitrogen(BUN) and serum creatinine(Cr) were detected to evaluate renal function. Superoxide dismutase(SOD) and lipid peroxidation product propylene glycol(MDA) were testified to evaluate oxidative stress in kidney. Renal histopathological grading was used to evaluate renal histology between each experimental group.Results:ATX preserved renal function in IR+ATX group compared with IR group reflected by significantly decreased level of BUN and Cr(P < 0.05). Compared with the IR group, the level of SOD increased significantly(P < 0.05) while the level of MDA decreased significantly(P < 0.05) in IR+ATX group. Renal histopathological score in IR+ATX group reduced significantly compared with IR group(P < 0.05).Conclusion:ATX is effective in preserving renal function and histology via antioxidant activity.