Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), a potentially fatal syndrome characterized by a rapid decline in kidney function. Excess production of superoxide contributes to the injury. We hypothesized that oral administration of a high dose of vitamin B12 (B12 - cyanocobalamin), which possesses a superoxide scavenging function, would protect kidneys against IRI and provide a safe means of treatment. Following unilateral renal IR surgery, C57BL/6J wild type (WT) mice were administered B12 via drinking water at a dose of 50 mg/L. After 5 days of the treatment, plasma B12 levels increased by 1.2-1.5x, and kidney B12 levels increased by 7-8x. IRI mice treated with B12 showed near normal renal function and morphology. Further, IRI-induced changes in RNA and protein markers of inflammation, fibrosis, apoptosis, and DNA damage response (DDR) were significantly attenuated by at least 50% compared to those in untreated mice. Moreover, the presence of B12 at 0.3 μM in the culture medium of mouse proximal tubular cells subjected to 3 hr of hypoxia followed by 1 hr of reperfusion in vitro showed similar protective effects, including increased cell viability and decreased reactive oxygen species (ROS) level. We conclude that a high dose of B12 protects against perfusion injury both in vivo and in vitro without observable adverse effects in mice and suggest that B12 merits evaluation as a treatment for I/R-mediated AKI in humans.

肾缺血/再灌注损伤（IRI）是急性肾损伤（AKI）的主要原因，急性肾损伤是一种潜在的致命综合征，其特征是肾功能迅速下降。超氧化物的过量产生会造成伤害。我们假设口服具有超氧化物清除功能的高剂量维生素B12（B12-氰钴胺）可以保护肾脏免受IRI感染并提供安全的治疗手段。在单侧肾脏IR手术后，通过饮用水以50 mg / L的剂量对C57BL / 6J野生型（WT）小鼠进行B12给药。治疗5天后，血浆B12水平增加了1.2-1.5倍，肾脏B12水平增加了7-8倍。用B12处理的IRI小鼠显示出接近正常的肾功能和形态。此外，IRI诱导的炎症，纤维化，与未治疗的小鼠相比，细胞凋亡和DNA损伤反应（DDR）显着减弱了至少50％。此外，小鼠近端肾小管细胞的培养基中存在0.3μM的B12，缺氧3小时，然后再灌注1小时体外显示出相似的保护作用，包括增加细胞活力和降低活性氧（ROS）水平。我们得出的结论是，高剂量的B12可以在体内和体外保护小鼠免受灌注损伤，而在小鼠中却没有可观察到的不良影响，并建议将B12作为I / R介导的AKI在人类中的治疗方法值得评估。