Unilateral ureteral obstruction (UUO) is an animal rodent model that allows the study of obstructive nephropathy in an accelerated manner. During UUO, tubular damage is induced, and alterations such as oxidative stress, inflammation, lipid metabolism, and mitochondrial impairment favor fibrosis development, leading to chronic kidney disease progression. Sulforaphane (SFN), an isothiocyanate derived from green cruciferous vegetables, might improve mitochondrial functions and lipid metabolism; however, its role in UUO has been poorly explored. Therefore, we aimed to determine the protective effect of SFN related to mitochondria and lipid metabolism in UUO. Our results showed that in UUO SFN decreased renal damage, attributed to increased mitochondrial biogenesis. We showed that SFN augmented peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and nuclear respiratory factor 1 (NRF1). The increase in biogenesis augmented the mitochondrial mass marker voltage-dependent anion channel (VDAC) and improved mitochondrial structure, as well as complex III (CIII), aconitase 2 (ACO2) and citrate synthase activities in UUO. In addition, lipid metabolism was improved, observed by the downregulation of cluster of differentiation 36 (CD36), sterol regulatory-element binding protein 1 (SREBP1), fatty acid synthase (FASN), and diacylglycerol O-acyltransferase 1 (DGAT1), which reduces triglyceride (TG) accumulation. Finally, restoring the mitochondrial structure reduced excessive fission by decreasing the fission protein dynamin-related protein-1 (DRP1). Autophagy flux was further restored by reducing beclin and sequestosome (p62) and increasing B-cell lymphoma 2 (Bcl2) and the ratio of microtubule-associated proteins 1A/1B light chain 3 II and I (LC3II/LC3I). These results reveal that SFN confers protection against UUO-induced kidney injury by targeting mitochondrial biogenesis, which also improves lipid metabolism.

中文翻译：

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萝卜硫素通过减轻线粒体和脂质代谢障碍来保护大鼠免受单侧输尿管梗阻引起的肾损伤

单侧输尿管梗阻 (UUO) 是一种啮齿动物模型，可以加速研究梗阻性肾病。在 UUO 期间，肾小管损伤被诱导，氧化应激、炎症、脂质代谢和线粒体损伤等改变有利于纤维化发展，导致慢性肾脏疾病进展。萝卜硫素 (SFN) 是一种从绿色十字花科蔬菜中提取的异硫氰酸酯，可能会改善线粒体功能和脂质代谢；然而，它在 UUO 中的作用却没有得到很好的探索。因此，我们旨在确定 SFN 对 UUO 中线粒体和脂质代谢的保护作用。我们的研究结果表明，在 UUO SFN 中，肾损伤减少，这归因于线粒体生物合成的增加。我们发现 SFN 增强了过氧化物酶体增殖物激活受体 γ 共激活因子 1α (PGC-1α) 和核呼吸因子 1 (NRF1)。生物发生的增加增强了线粒体质量标记电压依赖性阴离子通道 (VDAC) 并改善了线粒体结构，以及 UUO 中的复合物 III (CIII)、乌头酸酶 2 (ACO2) 和柠檬酸合酶活性。此外，通过分化簇 36 (CD36)、甾醇调节元件结合蛋白 1 (SREBP1)、脂肪酸合酶 (FASN) 和二酰基甘油 O-酰基转移酶 1 (DGAT1) 的下调观察到脂质代谢得到改善。减少甘油三酯（TG）的积累。最后，恢复线粒体结构通过降低裂变蛋白 dynamin-related protein-1 (DRP1) 来减少过度裂变。通过减少 beclin 和 sequestosome (p62) 和增加 B 细胞淋巴瘤 2 (Bcl2) 和微管相关蛋白 1A/1B 轻链 3 II 和 I (LC3II/LC3I) 的比例进一步恢复自噬通量。这些结果表明，SFN 通过靶向线粒体生物发生来保护 UUO 诱导的肾损伤，这也改善了脂质代谢。