Xiong Ying, Shang Bingzhen, Xu Siying, Zhao Ran, Gou He, Wang Chun
a Department of Cell Biology, Basic Medical College, Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Ministry of Education of China (Province-Ministry Co-Construct) , Liaoning University of Traditional Chinese Medicine , Shenyang , China ;
b Northeastern Yucai Foreign Language School , Shenyang , China ;
Ren Fail. 2016 Sep;38(8):1240-8. doi: 10.1080/0886022X.2016.1209380. Epub 2016 Jul 19.
Drug-induced renal injury is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-zhong-yi-qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in Asia as an alternative treatment to reduce the side effects of chemotherapy and also improve cancer survival. However, the mechanism is unknown. This study is designed to investigate the protective effect of BZYQD on 5-FU-induced renal injury in mice.
Mice were divided into four groups: the control, 5-FU, 5-FU + low, and high BZYQD group. Mice in the three latter groups were administered 5-FU (100 mg/kg/day, intraperitoneally) for six days, and in the 5-FU + low and high BZYQD groups were given BZYQD (1 or 2 g raw herb/kg/day, intragastrically) beginning four days before 5-FU and continuing until the termination of the experiment. The right kidney fixed in formalin for histological examination and the left was homogenized to measure the levels of apoptosis-related proteins and activities of oxidative stress-related biomarkers. Blood samples were collected for measuring renal function-related biochemical indices.
Renal morphology injury, increased urea nitrogen and creatinine concentration, and decreased SOD, CAT, and GSH-Px were all observed in 5-FU-administrated mice. However, BZYQD almost reversed the morphological injury as well as renal function-related indices and antioxidant enzyme activity.
These results suggest that BZYQD inhibits 5-FU-induced renal injury, possibly through the reduction of apoptosis and necrosis in renal tubular epithelial cells via the antioxidant mechanism. Henceforth, BZYQD may be a potential antioxidant against drug-induced oxidative stress.
药物性肾损伤是5-氟尿嘧啶（5-FU）治疗的一种严重毒性副作用。补中益气汤（BZYQD）是一种中药水提取物，在亚洲被广泛用作减少化疗副作用并提高癌症生存率的替代疗法。然而，其机制尚不清楚。本研究旨在探讨BZYQD对5-FU诱导的小鼠肾损伤的保护作用。
将小鼠分为四组：对照组、5-FU组、5-FU+低剂量BZYQD组和5-FU+高剂量BZYQD组。后三组小鼠连续6天腹腔注射5-FU（100mg/kg/天），5-FU+低剂量和高剂量BZYQD组在5-FU给药前4天开始灌胃给予BZYQD（1或2g生药/kg/天），并持续至实验结束。取右肾用福尔马林固定用于组织学检查，取左肾匀浆以测定凋亡相关蛋白水平和氧化应激相关生物标志物的活性。采集血样以测定肾功能相关生化指标。
在给予5-FU的小鼠中均观察到肾形态学损伤、尿素氮和肌酐浓度升高以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）活性降低。然而，BZYQD几乎逆转了形态学损伤以及肾功能相关指标和抗氧化酶活性。
这些结果表明，BZYQD可能通过抗氧化机制减少肾小管上皮细胞的凋亡和坏死，从而抑制5-FU诱导的肾损伤。因此，BZYQD可能是一种潜在的抗药物诱导氧化应激的抗氧化剂。
