Nuclear Technology Development Center (CDTN), Biological Science Institute - Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Department of Morphology, Biological Science Institute - Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Clin Sci (Lond). 2020 Dec 11;134(23):3093-3106. doi: 10.1042/CS20201022.
Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin-Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.
急性肾损伤(AKI)包括迅速发展的肾衰竭,与高死亡率相关。肾素-血管紧张素系统(RAS)在 AKI 中起着关键作用,因为过度活跃的 RAS 轴在疾病进展中产生主要的有害影响。在这种意义上,血管紧张素转换酶 2(ACE2)将血管紧张素 II(Ang II)转化为血管紧张素-(1-7)(Ang-(1-7))对于预防更差的临床结局非常重要。先前的研究报告了口服地拉佐嗪(DIZE),一种 ACE2 激活剂,在肾脏疾病模型中的有益作用。在本研究中,我们旨在评估 DIZE 在庆大霉素(GM)诱导的大鼠实验性 AKI 中的治疗效果。我们的研究结果表明,DIZE 通过增加 Ang-(1-7)和 ACE2 活性,降低 TNF-α,改善了肾功能和组织损伤。这些结果证实了 ACE2 激活作为治疗 AKI 的一种策略的潜力。