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Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity.

Abstract：

:Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p<0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Li J,Sun K,Ni L,Wang X,Wang D,Zhang J

doi

10.1016/j.taap.2011.11.020

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

376-83

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(11)00456-X

journal_volume

258

pub_type

杂志文章

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