The Open Toxicology Journal

2008, 2 : 1-6
Published online 2008 May 23. DOI: 10.2174/1874340400802010001
Publisher ID: TOTOXIJ-2-1

Therapeutic Alliance: Using N-(2,3,4,5,6-Pentahydroxylhex-1-yl)-NDithiocarbamate- L-Isoleucine Disodium to Improve the Toxicity and Survival of Cisplatin Receiving Mice

Yuji Wang , Ming Zhao , Guohui Cui , Chunying Cui , Jingfang Ju and Shiqi Peng
College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, P. R. China; Tel: 86- 10-8391-1528; Fax: 86-10-8391-1528; E-mail: sqpeng@bjmu.edu.cn; College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, P.R. China.

ABSTRACT

To reduce the toxicity of cisplatin N-(2,3,4,5,6-pentahydroxylhex-1-yl)-N-dithiocarbamate-L-isoleucine disodium (GID) based therapeutic alliance is investigated. For the proliferation of HepG2, Hela, MES-SA, HL60 and H1299 cells, 27μM of GID based therapeutic alliance gave comparable inhibition to cisplatin alone. For implanted tumor proliferation in mice, 1.667μmol/kg of GID based therapeutic alliance gave higher inhibition than cisplatin alone. For cisplatin receiving mice, this therapeutic alliance effectively reduces the platinum accumulations in the organs but does not affect the platinum level in the tumor tissue. Comparing to cisplatin alone, this therapeutic alliance not only increases urea and fecal platinum levels but also increases urea excretion. All the observations imply that GID based therapeutic alliance is capable of reducing the toxicity and supporting the anti-tumor potency of cisplatin.

Keywords:

Cisplatin, N-(2,3,4,5,6-Pentahydroxylhex-1-yl)-N-dithiocarbamate-L-isoleucine Disodium, Therapeutic Alliance, Anti-tumor, Toxicity.