Recent studies suggest that mitochondrial bioenergetics and oxidative stress alterations may be common mechanisms involved in the progression of renal damage. However, the evolution of the mitochondrial alterations over time and the possible effects that their prevention could have in the progression of renal damage are not clear. Folic acid (FA)-induced kidney damage is a widely used experimental model to induce acute kidney injury (AKI), which can evolve to chronic kidney disease (CKD). Therefore, it has been extensively applied to study the mechanisms involved in AKI-to-CKD transition. We previously demonstrated that one day after FA administration, N-acetyl-cysteine (NAC) pre-administration prevented the development of AKI induced by FA. Such therapeutic effect was related to mitochondrial preservation. In the present study, we characterized the temporal course of mitochondrial bioenergetics and redox state alterations along the progression of renal damage induced by FA. Mitochondrial function was studied at different time points and showed a sustained impairment in oxidative phosphorylation capacity and a decrease in β-oxidation, decoupling, mitochondrial membrane potential depolarization and a pro-oxidative state, attributed to the reduction in activity of complexes I and III and mitochondrial cristae effacement, thus favoring the transition from AKI to CKD. Furthermore, the mitochondrial protection by NAC administration before AKI prevented not only the long-term deterioration of mitochondrial function at the chronic stage, but also CKD development. Taken together, our results support the idea that the prevention of mitochondrial dysfunction during an AKI event can be a useful strategy to prevent the transition to CKD.

中文翻译：

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线粒体生物能量学的慢性损伤和β-氧化促进叶酸诱导的实验性AKI到CKD的转变。

最近的研究表明，线粒体生物能和氧化应激改变可能是肾脏损害进展的常见机制。然而，线粒体变化随时间的演变以及它们的预防可能对肾脏损害的进展可能尚不清楚。叶酸（FA）引起的肾脏损害是引起急性肾损伤（AKI）的广泛使用的实验模型，急性肾损伤可演变为慢性肾脏疾病（CKD）。因此，它已被广泛应用于研究AKI到CKD过渡的机制。我们先前证明，FA给药后一天，N-乙酰半胱氨酸（NAC）预先给药可防止FA诱导的AKI的发展。这种治疗效果与线粒体的保存有关。在目前的研究中，我们表征了线粒体生物能学的时间过程和氧化还原状态改变沿FA致肾损害的进展。在不同时间点研究了线粒体功能，结果表明氧化磷酸化能力持续受损，β-氧化，去偶联，线粒体膜电位去极化和前氧化态降低，这归因于复合物I和III和线粒体的ista痕消失，因此有利于从AKI到CKD的过渡。此外，在AKI之前通过NAC给予线粒体保护不仅防止了慢性阶段线粒体功能的长期恶化，而且还防止了CKD的发展。在一起