PROTECTION OF COENZYME Q-10 AGAINST CONTRAST-INDUCED ACUTE KIDNEY INJURY IN DIABETIC RATS

ABSTRACT Background: Diabetes Mellitus (DM) is an important risk factor for Contrast- induced acute kidney injury (CI-AKI). DM and CI-AKI results in oxidative damage and inflammation that can be reduce with treatment of coenzyme Q-10 (CoQ10). The aim of this study was to investigate the therapeutic potential of CoQ10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats submitted to the CI-AKI model. Methods: Wistar rats, male, randomized into four groups: Citrate- control animals, received citrate buffer (streptozotocin vehicle, 0.4 ml); Tween- control animals of CoQ10 treatment, received 1% Tween 80 (CoQ10 vehicle, 0.5 ml); DM- animals that received streptozotocin (60 mg/kg); DM+IC: DM animals, treated with iodinated contrast (IC, 6 ml/kg); DM+IC+CoQ10: DM animals treated with CoQ10 (10 mg/kg) and that received with IC (6 ml/kg). The protocols lasted 4 weeks. Were evaluated the renal function by inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis. Results: DM animals showed reduced renal function which was reflected with an increase of serum creatinine and significant reduced of inulin clearance, as well as a reduction on RBF, increased RVR and redox imbalance with a higher urinary peroxides, nitrate lipid peroxidation levels and depletion of thiols in renal tissue. IC treatment exacerbated theses changes in DM + IC. CoQ10 administration ameliorates renal function, prevented hemodynamic changes, neutralize oxidative damage and progression of the histologic damage in the DM+IC+CoQ10 group. Conclusion: This study demonstrated a renoprotection of CoQ10 in an experimental model of risk factor of DM for CI-AKI. CoQ10 presented an antioxidant effect on the CI-AKI in diabetic rats, by improving function and renal hemodynamics, preserving morphology and reducing oxidative stress. KEYWORDS: Diabetes Mellitus; Nephrotoxicity; Iodinated Contrast; Coenzyme Q-10.摘要 背景：糖尿病（Diabetes Mellitus, DM）是对比剂诱导急性肾损伤（Contrast-induced acute kidney injury, CI-AKI）的重要危险因素。糖尿病与CI-AKI可引发氧化损伤与炎症反应，而辅酶Q10（coenzyme Q-10, CoQ10）可通过干预缓解此类损伤。本研究旨在探讨辅酶Q10对构建CI-AKI模型的糖尿病大鼠肾功能、肾血流动力学、氧化应激状态及肾组织病理学的治疗潜力。 方法：将雄性Wistar大鼠随机分为四组，具体分组及干预如下：①枸橼酸盐对照组：给予枸橼酸盐缓冲液（链脲佐菌素溶剂，0.4 ml）；②吐温80对照组：给予1%吐温80溶液（CoQ10溶剂，0.5 ml）；③糖尿病组：给予链脲佐菌素（60 mg/kg）造模；④DM+IC组：糖尿病大鼠给予碘对比剂（IC，6 ml/kg）；⑤DM+IC+CoQ10组：糖尿病大鼠给予CoQ10（10 mg/kg）后再给予碘对比剂（6 ml/kg）。所有实验周期为4周。本研究通过以下指标开展评估：采用菊粉清除率与血清肌酐水平评价肾功能；通过肾血流量（renal blood flow, RBF）与肾血管阻力（renal vascular resistance, RVR）检测肾血流动力学；检测氧化应激相关标志物，包括尿过氧化物、硝酸盐、脂质过氧化产物、肾组织巯基水平，并进行肾组织病理学分析。 结果：糖尿病组大鼠肾功能出现明显减退，表现为血清肌酐水平升高、菊粉清除率显著降低，同时伴随肾血流量减少、肾血管阻力升高，氧化还原失衡：尿过氧化物与硝酸盐水平升高、脂质过氧化程度加剧，肾组织巯基水平耗竭。碘对比剂干预进一步加重了DM+IC组大鼠的上述病理变化。而DM+IC+CoQ10组大鼠经CoQ10干预后，肾功能得到改善，血流动力学异常得以纠正，氧化损伤被中和，组织病理学损伤进程也得到有效延缓。 结论：本研究证实，在以糖尿病作为CI-AKI危险因素的实验模型中，CoQ10具有明确的肾脏保护作用。CoQ10可通过改善肾功能与肾血流动力学、维持肾脏形态结构完整、减轻氧化应激，对糖尿病大鼠的CI-AKI发挥抗氧化保护效应。 关键词：糖尿病；肾毒性；碘对比剂；辅酶Q10。