Lee Joo-Ho, Lee Hyo-Jung, Lee Hyo-Jeong, Choi Won-Cheol, Yoon Seong-Woo, Ko Seong-Gyu, Ahn Kwang Seok, Choi Seung-Hoon, Ahn Kyoo-Seok, Lieske John C, Kim Sung-Hoon
College of Oriental Medicine, Cancer Preventive Material Development Research Center, Kyunghee University, 1 Hoegi-Dong Dongdaemun-Gu, Seoul 130-701, Republic of Korea.
Phytomedicine. 2009 Mar;16(2-3):188-97. doi: 10.1016/j.phymed.2008.10.009. Epub 2009 Jan 15.
Cisplatin-induced oxidative stress can cause liver and kidney damage, thus limiting therapeutic efficacy. Thus, in the present study, since Rhus verniciflua Stokes (RVS) containing flavonoids has antioxidant effects, we investigated whether it can protect cisplatin-induced toxicity in vitro and in vivo, The in vitro effects of RVS on the cell viability and reactive oxygen species (ROS) production were investigated using cisplatin-treated Madin-Darby Canine kidney (MDCK)-I renal cells. Its in vivo effects were also studied in BALB/c mice inoculated with CT-26 colon adenocarcinoma cells and treated with cisplatin with or without RVS. Liver and renal functions were assessed together with indices of tissue oxidation. RVS prevented cisplatin-induced cytotoxicity and ROS release against MDCK-I cells. RVS alone exerted modest antitumor activity against CT-26 cells. When used concurrently with cisplatin, RVS prevented the increases in serum blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and NO, while reducing liver and kidney tissue MDA content, and increasing catalase, glutathione (GSH), and superoxide dismutase (SOD) activities. Moreover, the antitumor efficacy of cisplatin was not altered by concurrent administration of RVS. These findings demonstrate that RVS prevents cisplatin-induced toxicity in vitro and in vivo via an antioxidant activity without hurting its antitumor effectiveness, suggesting that RVS can be usefully applied to the neoplastic patients as a combined chemopreventive agent with cisplatin.
顺铂诱导的氧化应激可导致肝和肾损伤,从而限制治疗效果。因此,在本研究中,由于含有黄酮类化合物的漆树(RVS)具有抗氧化作用,我们研究了它是否能在体外和体内保护顺铂诱导的毒性。使用顺铂处理的犬肾(MDCK)-I肾细胞研究了RVS对细胞活力和活性氧(ROS)产生的体外影响。还在接种CT-26结肠腺癌细胞并用或不用RVS处理顺铂的BALB/c小鼠中研究了其体内作用。评估肝功能和肾功能以及组织氧化指标。RVS可预防顺铂诱导的对MDCK-I细胞的细胞毒性和ROS释放。单独使用RVS对CT-26细胞具有适度的抗肿瘤活性。当与顺铂同时使用时,RVS可预防血清血尿素氮(BUN)、肌酐、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和NO的升高,同时降低肝和肾组织丙二醛(MDA)含量,并增加过氧化氢酶、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)活性。此外,同时给予RVS不会改变顺铂的抗肿瘤疗效。这些发现表明,RVS通过抗氧化活性在体外和体内预防顺铂诱导的毒性,而不会损害其抗肿瘤效果,这表明RVS可作为与顺铂联合的化学预防剂有效地应用于肿瘤患者。