Kim Jung-Yeon, Leem Jaechan, Hong Hyo-Lim
Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea.
Department of Internal Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea.
Antioxidants (Basel). 2020 Jul 4;9(7):585. doi: 10.3390/antiox9070585.
Inflammation and oxidative stress plays an essential role in the pathophysiology of sepsis-associated acute kidney injury (AKI). SPA0355, a thiourea analogue, has been shown to display beneficial effects against a variety of inflammatory diseases arising from its anti-inflammatory and anti-oxidant properties. However, the potential protective effects of SPA0355 against lipopolysaccharide (LPS)-induced AKI have not been explored. The aim of this study was to evaluate the effects of SPA0355 on LPS-induced AKI and investigate its underlying mechanisms. We found that renal dysfunction and histological abnormalities after LPS injection were significantly ameliorated by SPA0355. The compound also reduced renal expression of tubular injury markers. Mechanistically, SPA0355 significantly suppressed plasma and tissue levels of inflammatory cytokines and immune cell infiltration with inhibition of nuclear factor kappa-B p65 signaling. In addition, elevated levels of 4-hydroxynonenal and malondialdehyde after LPS injection were significantly decreased by SPA0355. The compound also regulated expression of pro-oxidant and antioxidant enzymes after LPS injection. Moreover, SPA0355 attenuated LPS-induced tubular cell apoptosis via inhibition of p53 signaling pathway. Altogether, these results suggest that SPA0355 protects against LPS-induced AKI through suppressing inflammation, oxidative stress, and tubular cell apoptosis and might be a potential preventive option for the disease.
炎症和氧化应激在脓毒症相关性急性肾损伤（AKI）的病理生理学中起着至关重要的作用。硫脲类似物SPA0355已被证明因其抗炎和抗氧化特性，对多种炎症性疾病具有有益作用。然而，SPA0355对脂多糖（LPS）诱导的AKI的潜在保护作用尚未得到探索。本研究的目的是评估SPA0355对LPS诱导的AKI的影响，并探究其潜在机制。我们发现，注射LPS后出现的肾功能障碍和组织学异常通过SPA0355得到了显著改善。该化合物还降低了肾小管损伤标志物的肾脏表达。从机制上讲，SPA0355通过抑制核因子κB p65信号通路，显著抑制了炎症细胞因子的血浆和组织水平以及免疫细胞浸润。此外，注射LPS后升高的4-羟基壬烯醛和丙二醛水平通过SPA0355显著降低。该化合物还调节了注射LPS后促氧化剂和抗氧化酶的表达。此外，SPA0355通过抑制p53信号通路减轻了LPS诱导的肾小管细胞凋亡。总之，这些结果表明，SPA通过抑制炎症、氧化应激和肾小管细胞凋亡来保护机体免受LPS诱导的AKI，可能是该疾病一种潜在的预防选择。
