Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, 11571, Egypt.
Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Int Immunopharmacol. 2023 Oct;123:110777. doi: 10.1016/j.intimp.2023.110777. Epub 2023 Aug 9.
Folic acid (FA)-induced acute renal injury (AKI) is a commonly and highly reproducible model used to study AKI. The current study aims to evaluate the possible protective effects of sulforaphane (SFN) against FA-induced renal damage and explore the underlying molecular mechanism.
The animals were divided into four groups (6 rats/group) as follows: normal group (received vehicle, p.o.), FA group (received 250 mg/kg, i.p.), SFN low dose group (received 15 mg/kg, p.o. plus FA 250 mg/kg, i.p.), SFN high dose group (30 mg/kg, p.o. plus FA 250 mg/kg, i.p.). At the end of the experiment, serum samples and kidney tissues were obtained to perform biochemical, molecular, and histopathological investigations.
The present study showed that FA-caused AKI was confirmed by a significant elevation of kidney function biomarkers serum levels accompanied by an observation of histopathologic changes. Interestingly, SFN-administration significantly improved kidney function, reduced oxidative stress markers; MDA, NADPH oxidase, MPO, iNOS with up-regulation of GSH, GCLM, GPX4, SOD, NQO1, HO-1 and Nrf2 levels. SFN also downregulated proinflammatory markers. The results also demonstrated the anti-apoptotic effect of SFN through its ability to increase the antiapoptotic Bcl-2 protein and to decrease caspase-3. Moreover, SFN significantly decreased the relative expression of JNK, ERK-1/2, IRF3, and p38MAPK as compared to the FA-nephrotoxic group.
The present study revealed that SFN possess an antioxidant, anti-inflammatory and antiapoptotic activity by modulating caspase-3, Bcl-2, ERK1/2, JNK, GCLM, NQO1, GPX4, Nrf2, HO-1 and P38 signaling pathways in a dose dependent manner which provides a potential therapeutic strategy for preventing FA-induced AKI.
叶酸（FA）诱导的急性肾损伤（AKI）是一种常用且可高度重现的 AKI 模型。本研究旨在评估萝卜硫素（SFN）对 FA 诱导的肾损伤的可能保护作用，并探讨其潜在的分子机制。
将动物分为四组（每组 6 只大鼠）：正常组（给予载体，口服）、FA 组（给予 250mg/kg，腹腔注射）、SFN 低剂量组（给予 15mg/kg，口服加 FA 250mg/kg，腹腔注射）、SFN 高剂量组（30mg/kg，口服加 FA 250mg/kg，腹腔注射）。实验结束时，采集血清样本和肾组织进行生化、分子和组织病理学研究。
本研究表明，FA 引起的 AKI 是通过显著升高血清肾功标志物水平并观察到组织病理学变化来证实的。有趣的是，SFN 给药可显著改善肾功能，降低氧化应激标志物 MDA、NADPH 氧化酶、MPO、iNOS，同时上调 GSH、GCLM、GPX4、SOD、NQO1、HO-1 和 Nrf2 水平。SFN 还下调了促炎标志物。研究结果还表明，SFN 通过增加抗凋亡蛋白 Bcl-2 和减少 caspase-3 发挥抗凋亡作用。此外，与 FA 肾毒性组相比，SFN 显著降低了 JNK、ERK-1/2、IRF3 和 p38MAPK 的相对表达。
本研究表明，SFN 通过调节 caspase-3、Bcl-2、ERK1/2、JNK、GCLM、NQO1、GPX4、Nrf2、HO-1 和 P38 信号通路，具有抗氧化、抗炎和抗凋亡活性，这种作用呈剂量依赖性，为预防 FA 诱导的 AKI 提供了一种潜在的治疗策略。
