Attenuating the toxicity of cisplatin by using selenosulfate with reduced risk of selenium toxicity as compared with selenite

Journal Article · Fri Feb 01 04:00:00 EST 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2007.09.010· OSTI ID:21077906

Dungeng, Peng; Hongjuan, Lu; Qingliang, Liu ^[1]

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1. University of Science and Technology of China, Hefei 230052, Anhui (China)

It has been reported that high doses of sodium selenite can reduce side effects of cisplatin (CDDP) without compromising its antitumor activity, thus substantially enhancing the cure rate in tumor-bearing mice. However, the toxicity of selenite at high doses should be a concern. The present study revealed that selenosulfate had much lower toxicity, but possessed equal efficacy in selenium (Se) utilization, as compared with selenite at similar doses when used for the intervention of CDDP. In addition, Se accumulation in whole blood and kidney of mice treated with selenosulfate was highly correlated with the survival rate of mice treated with CDDP (both r > 0.96 and both p < 0.05), suggesting that whole blood Se is a potential clinical biomarker to predict host tolerance to CDDP. In either Se-deficient or -sufficient mice bearing solid tumors of hepatoma 22 (H22), selenosulfate did not disturb the therapeutic effect of CDDP on tumors but effectively attenuated the toxicity of CDDP. Furthermore, in a highly malignant cancer model, with Se-sufficient mice bearing ascitic H22 cells, 8 or 10 mg/kg CDDP alone only achieved a null or 25% cure rate, whereas coadministration of selenosulfate with the above two doses of CDDP achieved cure rates of 87.5% or 75%. These results together argue for consideration of selenosulfate as an agent to enhance the therapeutic efficacy of CDDP.

• OSTI ID: 21077906
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 226; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL MARKERS
BLOOD
DOSES
HEALTH HAZARDS
HEPATOMAS
KIDNEYS
MICE
SELENITES
SELENIUM
SIDE EFFECTS
SODIUM
TOXICITY