Experimental Laboratory of Animal Models, School of Nursing, University of Sao Paulo, Sao Paulo 05403-000, Brazil.
Biomed Res Int. 2020 Nov 17;2020:1830934. doi: 10.1155/2020/1830934. eCollection 2020.
Iodinated contrast (IC) is a leading cause of hospital-based acute kidney injury (AKI). Contrast-induced acute kidney injury (CI-AKI) is a decline in renal function due to iodinated contrast administration and occurs more frequently in individuals with increasingly common risk factors, such as diabetes mellitus (DM). Physical training (PT) can have renoprotective effects on CI-AKI in diabetic nephropathy. The aim of this study was to evaluate the injury in kidneys of diabetic rats submitted to treatment with IC, evaluating the impact of PT on hemodynamics and renal function in addition to oxidative profile in diabetic rats submitted to IC-AKI.
Adult male Wistar rats are randomized into four groups: citrate ( = 7): control group, citrate buffer (streptozotocin-STZ vehicle), intravenous tail (iv), single dose; DM ( = 7): STZ, 60 mg/kg, iv, single dose; DM+IC ( = 7): DM rats treated with IC (sodium meglumine ioxithalamate, 6 mL/kg, intraperitoneal (ip), single dose); DM+IC+PT ( = 7): DM rats treated with IC as mentioned and submitted to physical training. Renal function parameters (inulin clearance, neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, and urinary albumin), hemodynamics (renal blood flow and renal vascular resistance), and oxidative profile (urinary peroxides, urinary TBARS, urinary nitric oxide, and renal tissue thiols) were evaluated.
It was possible to observe a decrease in inulin clearance, renal blood flow, and thiols in renal tissue accompanied by an increase in urinary flow, serum creatinine, urinary albumin, renal vascular resistance, urinary peroxides, urinary nitrate, and TBARS in the DM group compared to the citrate group. The DM+IC group showed a reduction in inulin clearance, and the renal dysfunction was also seen by the increased NGAL. Renal hemodynamics and oxidative profile compared were also worsened in the DM group. PT improved renal function by increasing renal blood flow and thiol levels in renal tissue and reduced renal vascular resistance, metabolites of reactive oxygen, nitrogen species, and lipid peroxidation in the DM+IC+PT group compared to DM+IC.
Our results confirmed that DM induction increases renal vulnerability to the toxicity of IC and an association between DM with IC predisposes to severe AKI with reduced renal function alongside with renal hemodynamic alterations and oxidative mechanism of injury. The PT showed a renoprotective effect in DM animals subjected to damage with IC by modulating renal hemodynamics and oxidative profile, confirming a potential to modify the risk of CI-AKI when diabetes mellitus is present.
碘造影剂（IC）是导致医院获得性急性肾损伤（AKI）的主要原因。造影剂诱导的急性肾损伤（CI-AKI）是由于碘造影剂的给予而导致的肾功能下降，并且在具有越来越多常见危险因素（如糖尿病（DM））的个体中更频繁地发生。身体训练（PT）对糖尿病肾病中的 CI-AKI 具有肾脏保护作用。本研究的目的是评估接受 IC 治疗的糖尿病大鼠肾脏的损伤，评估 PT 对糖尿病大鼠肾脏功能和氧化谱的影响。
成年雄性 Wistar 大鼠随机分为四组：柠檬酸盐（ = 7）：对照组，柠檬酸盐缓冲液（链脲佐菌素-STZ 载体），静脉尾（iv），单次剂量；DM（ = 7）：STZ，60mg/kg，iv，单次剂量；DM+IC（ = 7）：DM 大鼠用 IC（碘海醇，6mL/kg，腹腔内（ip），单次剂量）治疗；DM+IC+PT（ = 7）：DM 大鼠用 IC 治疗，如前所述，并进行身体训练。评估肾功能参数（菊粉清除率、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、血清肌酐和尿白蛋白）、血流动力学（肾血流量和肾血管阻力）和氧化谱（尿过氧化物、尿 TBARS、尿一氧化氮和肾组织硫醇）。
与柠檬酸盐组相比，DM 组的菊粉清除率、肾血流量和肾组织中的硫醇降低，同时尿流量、血清肌酐、尿白蛋白、肾血管阻力、尿过氧化物、尿硝酸盐和 TBARS 增加。DM+IC 组的菊粉清除率降低，肾功能障碍也通过增加 NGAL 观察到。与 DM 组相比，DM+IC 组的肾血流动力学和氧化谱也恶化。与 DM+IC 组相比，PT 通过增加肾血流量和肾组织中的硫醇水平以及降低肾血管阻力、活性氧、氮物种和脂质过氧化代谢物，改善了 DM+IC+PT 组的肾功能。
我们的结果证实，DM 诱导增加了肾脏对 IC 毒性的易感性，并且 DM 与 IC 的联合使糖尿病动物更容易发生严重的 AKI，伴有肾功能障碍以及肾损伤的氧化机制。PT 通过调节肾血流动力学和氧化谱对 DM 动物接受 IC 损伤显示出肾脏保护作用，证实了当存在糖尿病时，有改变 CI-AKI 风险的潜力。
