Accumulation, fractionation, and analysis of platinum in toxicologically affected tissues after cisplatin, oxaliplatin, and carboplatin administration.
Antitumoral Pt-containing drugs present side effects like nephrotoxicity and ototoxicity. Several systematic experiments have been carried out with Wistar rats treated with cisplatin, carboplatin, and oxaliplatin to study Pt-drugs accumulation and elimination, and Pt-biomolecule distribution in the cells and cytosols of ear, kidney, and liver. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis shows a cisplatin accumulation capability between oxaliplatin (the highest) and carboplatin (the lowest). The maximum concentration of Pt in all the organs studied was achieved around the first week after cisplatin treatment. During the first 30 days, the elimination was very fast, decreasing in the subsequent 60 days in all the organs. Analysis of cytosols by liquid chromatography (LC)-ICP-MS showed an analogous behavior. In most samples, the distribution of the three drugs in the cellular and cytosolic fractions was similar for all the tissues. For kidney and ear, approximately 60% and 30%, respectively, of the metal accumulated was present in the cytosol, the cytosolic fractions smaller than 50 KDa being especially important. Cisplatin-biomolecule interaction strength under denaturing conditions was evaluated by LC-ICP-MS and showed a quite strong bond.
Esteban-Fernández
D
D
Department of Analytical Chemistry, University Complutense of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
Verdaguer
J M
JM
Ramírez-Camacho
R
R
Palacios
M A
MA
Gómez-Gómez
M M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000032:analysis / Q000493:pharmacokinetics; D002458:Cell Fractionation; D002945:Cisplatin / Q000032:analysis / Q000493:pharmacokinetics; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D007758:Ear, Inner / Q000737:chemistry / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D009944:Organoplatinum Compounds / Q000032:analysis / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D010984:Platinum / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D016190:Carboplatin; D002945:Cisplatin