Rhus verniciflua Stokes prevents cisplatin-induced cytotoxicity and reactive oxygen species production in MDCK-I renal cells and intact mice.
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.
Lee
Joo-Ho
JH
College of Oriental Medicine, Cancer Preventive Material Development Research Center, Kyunghee University, 1 Hoegi-Dong Dongdaemun-Gu, Seoul 130-701, Republic of Korea.
Lee
Hyo-Jung
HJ
Lee
Hyo-Jeong
HJ
Choi
Won-Cheol
WC
Yoon
Seong-Woo
SW
Ko
Seong-Gyu
SG
Ahn
Kwang Seok
KS
Choi
Seung-Hoon
SH
Ahn
Kyoo-Seok
KS
Lieske
John C
JC
Kim
Sung-Hoon
SH
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy; D004285:Dogs; D004798:Enzymes / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D029045:Rhus
D000970:Antineoplastic Agents; D000975:Antioxidants; D004798:Enzymes; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D002945:Cisplatin