Effect of astaxanthin intervention on contrast-induced acute kidney injury in experimental rats

Abstract

Objective To explore the protective effect and mechanism of astaxanthin (AST) on the acute kidney injury induced by iohexol in rats. Method Thirty rats were randomly divided into five groups: control group (Ctrl); iohexol group (CM); astaxanthin group (AST, 100 mg/kg), low astaxanthin dose group (LAST+CM, 50 mg/kg) and high astaxanthin dose group (HAST+CM, 100 mg/kg), 6 in each group. The rats in AST, LAST+CM, HAST+CM groups were administrated with AST by oral gavages using an intubation needle for 10 consecutive days. The rats in Ctrl and CM groups rats in Ctrl, CM groups were given with dissolvant instead in equal volume. Except for the Ctrl and AST groups, on day 8, rats were given indomethacin, L-NAME and iohexol in their femoral vein under chloral hydrate anesthesia to build a contrast induced-nephropathy (CIN) model. At the end of the experiment (72 h after CIN induction), all rats were sacrificed. The Scr level, BUN level, renal histology, renal tissue activities in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Glutathione (GSH) and level of malondialdehyde (MDA) were performed. Apoptosis of renal cells was detected by Bcl-2, Bax and Caspase-3 p17 with Western blot. Results Compared with Ctrl group, the levels of Scr, BUN were significantly increased in CM group (all P <0.01); while compared with CM group, the indicators were decreased in treatment groups (P <0.01). Renal tubular structure damage, medulla congestion, loss of brush border, vacuolar degeneration, apoptosis and proteinaceous casts were observed in the CM group, and the renal injury scores were higher compared with Ctrl group (P <0.05), however, administrated with AST could significantly improve the changes (P <0.05). Oxidative stress indicators showed that MDA level were increased while SOD, GPx, GSH activities were significantly decreased at CM group (all P <0.05), and the indicators above were ameliorated in treatment groups (all P <0.05). Western blot showed that the expression of Bcl-2 was down-regulated while the Bax, Caspase 3 p17 was up-regulated respectively at CM group (P <0.05), while the HAST+CM group could prevent the changes. Conclusions Iohexol can results in oxidative stress increased in kidney, which activate Caspase-3 p17 signal path, down-regulated Bcl-2 expression, up-regulated Bax expression respectively, and lead to cell apoptosis. AST can ameliorate the changes, especially with high AST dose, which suggest that the possible protection mechanism is by ameliorating oxidative stress and inhibiting apoptosis pathways. Key words: Acute renal injury; Oxidative stress; Cell apoptosis; Astaxanthin