In:
Experimental Biology and Medicine, SAGE Publications, Vol. 231, No. 10 ( 2006-11), p. 1638-1645
Abstract:
The anticancer drug cisplatin can cause permanent inner ear damage. We have determined the second-order degradation rate constant, k NU , of cisplatin and its more toxic monohydrated complex (MHC) in the presence of each of the sulfur-containing nucleophiles N-acetyl-l-cysteine, l-cysteine methyl ester, 1,3-dimethyl-2-thiourea, d-methionine, and thiosulfate, compounds that are under evaluation for local administration to prevent cisplatin-induced ototoxicity. MHC was isolated from a hydrolysis solution of cisplatin using liquid chromatography (LC). The degradations were evaluated by measuring the disappearance of MHC and cisplatin at 37°C and pH 7.4 in the presence of each of the nucleophiles using LC and photometric detection. The k NU of MHC and of cisplatin was 0.044 M 1 sec 1 and 0.012 M 1 sec 1 with N-acetyl-l-cysteine, 0.24 M 1 sec 1 and 0.067 M 1 sec 1 with l-cysteine methyl ester, 0.16 M 1 sec 1 and 0.074 M 1 sec 1 with 1,3-dimethyl-2-thiourea, 0.070 M 1 sec 1 and 0.069 M 1 sec 1 with d-methionine, and 3.9 M 1 sec 1 and 0.091 M 1 sec 1 with thiosulfate, respectively. Our results suggest that thiosulfate, as being the strongest nucleophile, is a promising candidate for local application in order to reduce the inner ear content of MHC and cisplatin. However, otoprotection is a multifactorial event, and it remains to be established how important nucleophilicity is for the effectiveness of the protecting agent.
Type of Medium:
Online Resource
ISSN:
1535-3702
,
1535-3699
DOI:
10.1177/153537020623101009
Language:
English
Publisher:
SAGE Publications
Publication Date:
2006
detail.hit.zdb_id:
2020856-X
SSG:
12
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