Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity.
Cisplatin is a highly effective anti-cancer chemotherapeutic agent; however, its clinical use is severely limited by serious side effects, of which nephrotoxicity is the most important. In this study, we investigated whether Qiong-Yu-Gao (QYG), a popular traditional Chinese medicinal formula described 840 years ago, exhibits protective effects against cisplatin-induced renal toxicity. Using a mouse model of cisplatin-induced renal dysfunction, we observed that pretreatment with QYG attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels, ameliorated renal tubular lesions, reduced apoptosis, and accelerated tubular cell regeneration. Cisplatin-mediated elevations in tumor necrosis factor alpha (TNF-α) mRNA, interleukin-1 beta (IL-1β) mRNA, and cyclooxygenase-2 (COX-2) protein in the kidney were also significantly suppressed by QYG treatment. Furthermore, QYG reduced platinum accumulation in the kidney by decreasing the expression of copper transporter 1 and organic cation transporter 2. An in vivo study using implanted Lewis lung cancer cells revealed that concurrent administration of QYG and cisplatin did not alter the anti-tumor activity of cisplatin. Our findings suggest that the traditional Chinese medicinal formula QYG inhibits cisplatin toxicity by several mechanisms that act simultaneously, without compromising its therapeutic efficacy. Therefore, QYG may be useful in the clinic as a protective agent to prevent cisplatin-induced nephrotoxicity.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Zhi-Ying
ZY
Teng
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Xiao-Lan
XL
Cheng
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Xue-Ting
XT
Cai
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Yang
Y
Yang
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Xiao-Yan
XY
Sun
Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China.
Jin-Di
JD
Xu
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Wu-Guang
WG
Lu
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Jiao
J
Chen
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Chun-Ping
CP
Hu
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Qian
Q
Zhou
Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Xiao-Ning
XN
Wang
Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China.
Song-Lin
SL
Li
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
Peng
P
Cao
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000096:biosynthesis; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004365:Drugs, Chinese Herbal; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D002945:Cisplatin