Wu Tsai-Kun, Wei Chyou-Wei, Pan Ying-Ru, Cherng Shur-Hueih, Chang Wei-Jung, Wang Hsueh-Fang, Yu Yung-Luen
The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, Taiwan, R.O.C.
Deparment of Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
Mol Med Rep. 2015 Oct;12(4):6086-92. doi: 10.3892/mmr.2015.4167. Epub 2015 Aug 3.
Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AA‑induced cytotoxicity is associated with increases in oxidative stress and caspase‑3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspase‑dependent and ‑independent pathways. It is desirable to identify means of inhibiting AA‑induced renal damage; therefore, the present study applied an anti‑oxidative nutrient, vitamin C, to test whether it can be employed to reduce AA‑induced cell cytotoxicity. The results showed that vitamin C decreased AA‑induced H2O2 levels, caspase‑3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AA‑induced increases of the H2O2 ratio resulted in renal tubular cell death via caspase‑dependent and ‑independent pathways, and that vitamin C can decrease AA‑induced increases in H2O2 levels and caspase‑3 activity to attenuate AA‑induced cell cytotoxicity.
马兜铃酸(AA)是包括细辛和马兜铃在内的中药材的一种成分,长期以来一直用于传统中药。最近的研究发现,AA具有细胞毒性作用,可导致肾病。这些研究表明,AA诱导的细胞毒性与氧化应激增加和半胱天冬酶-3激活有关。本研究进一步证明,AA主要提高H2O2比率,导致氧化应激增加。此外,结果表明,AA可通过半胱天冬酶依赖性和非依赖性途径诱导细胞死亡。确定抑制AA诱导的肾损伤的方法是可取的;因此,本研究应用了一种抗氧化营养素维生素C,以测试它是否可用于降低AA诱导的细胞毒性。结果表明,维生素C降低了AA诱导的肾小管细胞中H2O2水平、半胱天冬酶-3活性和细胞毒性。总之,本研究首次证明,AA诱导的H2O2比率增加通过半胱天冬酶依赖性和非依赖性途径导致肾小管细胞死亡,并且维生素C可以降低AA诱导的H2O2水平和半胱天冬酶-3活性增加,以减轻AA诱导的细胞毒性。