Jump to main content
Jump to site search

Issue 3, 2014
Previous Article Next Article

Chemoprotection by D-methionine against cisplatin-induced side-effects: insight from in vitro studies using human plasma

Author affiliations

Abstract

Animal studies have shown that the nephrotoxicity and ototoxicity of the anti-cancer drug cisplatin (CP) can be ameliorated by the co-administration with D-methionine. The molecular mechanisms of this activity, however, are not well understood. Since CP is intravenously administered, the underlying chemistry may involve the interaction of CP-derived Pt-species with D-methionine in the bloodstream. Our previous studies have shown that the chemoprotective agents N-acetyl-L-cysteine and sodium thiosulfate modulate the metabolism of CP in human plasma in vitro, albeit in a different manner. Using a metallomics approach, we show that the incubation of human plasma with D-methionine and CP (molar ratio of 20 : 1) leads to the formation of a Pt–D-methionine complex independent of the order of addition. These results were corroborated by analogous experiments that were carried out using PBS-buffer instead of plasma. In addition, CP and D-methionine were added simultaneously to PBS-buffer and samples were analyzed at certain time intervals by the same metallomics method and LC-ESI-MS over a ∼21 h time period. Whereas the intermediate [Pt(NH3)Cl(D-methionine)]+ species was detected between 1–4 h, only the terminal [Pt(D-methionine)2]+ complex was present 21 h later. Combined, these studies demonstrate that in plasma and at the 20 : 1 D-methionine : CP molar ratio, an early CP hydrolysis product reacts with D-methionine to form a 1 : 1 complex that is followed by the formation of a 2 : 1 compound at a later time point. The formation of these Pt–D-methionine species may therefore play an important role in the processes by which D-methionine protects mammalian organisms against CP-induced toxicities.

Graphical abstract: Chemoprotection by d-methionine against cisplatin-induced side-effects: insight from in vitro studies using human plasma

Back to tab navigation

Supplementary files

Publication details

The article was received on 31 Aug 2013, accepted on 18 Nov 2013 and first published on 19 Nov 2013


Article type: Paper
DOI: 10.1039/C3MT00238A
Metallomics, 2014,6, 532-541

  •   Request permissions

    Chemoprotection by D-methionine against cisplatin-induced side-effects: insight from in vitro studies using human plasma

    M. Sooriyaarachchi, W. M. White, A. Narendran and J. Gailer, Metallomics, 2014, 6, 532
    DOI: 10.1039/C3MT00238A

Search articles by author

Spotlight

Advertisements