Arsenic trioxide (ATO)-induced renal toxicity through oxidative stress and apoptosis restricts the therapeutic action of acute myelogenous leukemia. Crocetin (Crt) possesses antioxidant and antiapoptosis properties, and has certain renal protective effects, but it has not been reported that it has protective effect on renal injury caused by ATO. The current study explored the effects and mechanisms of Crt on kidney damage induced by ATO. Fifty Sprague-Dawley rats were randomly divided into five groups. Adult rats were given Crt concurrently with ATO for 1 week. On the 8th day, rats were killed and blood and kidney tissues were collected. Histopathological changes were measured, and kidney tissues and serum were used to determine renal function and antioxidant enzyme activity. In addition, the protein expression levels of P-PI3K, PI3K, P-AKT, AKT, CytC, Bax, Bcl-2 and Caspase-3 were determined via western blot analysis. Results revealed ATO induced renal morphological alterations and activated serum BUN and CRE. Compared with the control group, ROS, MDA, IL-1β, TNF-α, protein carbonyls (PC), lipid hydroperoxides (LOOH) and arsenic concentration levels were found to be significantly increased and SOD, CAT, GSH-Px, GSH and total sulphydryl groups (TSH) levels were attenuated in the ATO group. Crt markedly reduced oxidative stress in ATO-induced nephrotoxicity. Further, ATO induced apoptosis by significantly enhancing CytC, Bax and Caspase-3 and inhibiting Bcl-2. Administration with Crt markedly improved the expression of apoptosis factor. Moreover, Crt treatment stimulated the expressions of P-PI3K, PI3K, P-AKT, AKT induced by ATO. This study indicates Crt could prevent renal injury caused by ATO through inhibiting oxidative stress, inflammation and apoptosis, and its mechanism may be related to activation of PI3K/Akt signaling pathway.

三氧化二砷（ATO）通过氧化应激和细胞凋亡诱导的肾脏毒性限制了急性粒细胞性白血病的治疗作用。Crocetin（Crt）具有抗氧化和抗凋亡的特性，并具有一定的肾脏保护作用，但尚未见报道对ATO引起的肾脏损伤具有保护作用。目前的研究探索了Crt对ATO引起的肾脏损害的作用和机制。将五十只Sprague-Dawley大鼠随机分为五组。成年大鼠与ATO同时接受Crt治疗1周。在第8天，处死大鼠并收集血液和肾脏组织。测量组织病理学变化，并使用肾脏组织和血清测定肾功能和抗氧化酶活性。此外，P-PI3K，PI3K，P-AKT，AKT，通过蛋白质印迹分析确定CytC，Bax，Bcl-2和Caspase-3。结果显示，ATO引起肾脏形态改变，并激活血清BUN和CRE。与对照组相比，发现ROS，MDA，IL-1β，TNF-α，蛋白羰基（PC），脂质氢过氧化物（LOOH）和砷浓度水平显着升高，并且SOD，CAT，GSH-Px，GSH和在ATO组中总的硫代硫酸酯（TSH）水平降低。Crt显着降低了ATO引起的肾毒性中的氧化应激。此外，ATO通过显着增强CytC，Bax和Caspase-3并抑制Bcl-2诱导凋亡。Crt的给药显着改善了凋亡因子的表达。而且，Crt处理刺激了由ATO诱导的P-PI3K，PI3K，P-AKT，AKT的表达。