Xi Yan, Chi Zhongchao, Tao Xufeng, Zhai Xiaohan, Zhao Zirui, Ren Jiaqi, Yang Shilei, Dong Deshi
Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Pharmacy, Third People's Hospital of Dalian, Dalian, China.
Environ Toxicol. 2023 May;38(5):1153-1161. doi: 10.1002/tox.23755. Epub 2023 Feb 22.
Clinical application of doxorubicin is limited because of its potential side effects. The present study examined whether naringin had protective actions on doxorubicin-induced liver injury. Male BALB/c mice and alpha mouse liver 12 (AML-12) cells were used in this paper. The results showed that AML-12 cells treated with naringin significantly reduced cell injury, reactive oxygen species release and apoptosis level; Moreover, naringin notably alleviated liver injury by decreasing aspartate transaminase, alanine transaminase and malondialdehyde, and increasing superoxide dismutase, glutathione and catalase levels. Mechanism researches indicated that naringin increased the expression levels of sirtuin 1 (SIRT1), and inhibited the downstream inflammatory, apoptotic and oxidative stress signaling pathways. Further validation was obtained by knocking down SIRT1 in vitro, which proved the effects of naringin on doxorubicin-induced liver injury. Therefore, naringin is a valuable lead compound for preventing doxorubicin-induced liver damage by reducing oxidative stress, inflammation, and apoptosis via up-regulation of SIRT1.
由于阿霉素存在潜在副作用，其临床应用受到限制。本研究检测了柚皮苷对阿霉素诱导的肝损伤是否具有保护作用。本文使用了雄性BALB/c小鼠和α小鼠肝脏12（AML-12）细胞。结果显示，用柚皮苷处理的AML-12细胞显著降低了细胞损伤、活性氧释放和凋亡水平；此外，柚皮苷通过降低天冬氨酸转氨酶、丙氨酸转氨酶和丙二醛水平，并提高超氧化物歧化酶、谷胱甘肽和过氧化氢酶水平，显著减轻了肝损伤。机制研究表明，柚皮苷增加了沉默调节蛋白1（SIRT1）的表达水平，并抑制了下游炎症、凋亡和氧化应激信号通路。通过体外敲低SIRT1获得了进一步验证，这证明了柚皮苷对阿霉素诱导的肝损伤的作用。因此，柚皮苷是一种有价值的先导化合物，可通过上调SIRT1来减轻氧化应激、炎症和凋亡，从而预防阿霉素诱导的肝损伤。
