Abstract
Oleuropein (Ole) has been claimed to mitigate cisplatin (CP)-induced acute injury in kidney and liver of mice. In vitro reactivity of hydrated CP species with Ole, and an Ole metabolite, hydroxytyrosol (HT), is of great interest as the preliminary step for gathering in vivo information on the possible physiological role of the Ole/HT-cis-diammineplatinum(II) (Ole/HT-cis-DAP) conjugate. Reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry using a linear ion trap instrument (RPLC/ESI-MS) and tandem mass (MS/MS) measurements, both in positive and negative ion mode, revealed the molecular identity of platinum-based conjugates. The Ole-cis-DAP conjugate (i.e., C25 H36 N2 O13 PtII ) features two cis-ammine non-leaving ligands and a bidentate catechol ligand moiety belonging to Ole; the coordination of the central Pt(II) is square-planar with non-equivalent bond angles compared with the ideal arrangement of 90°. HT, the free Ole metabolite excreted in human urine, acts as bidentate O,O-donor ligand of cis-DAP as well. The first evidence, together with structural information, is provided about the in vitro formation of a conjugate between cis-DAP and Ole or its urinary metabolite HT. Presuming that such conjugates are also generated in vivo, the mechanisms by which they might contribute to reduce CP toxicity remain to be elucidated.
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