Z Gastroenterol 2011; 49 - A5
DOI: 10.1055/s-0031-1278436

Changes in element homeostasis during cisplatin treatment in different organs

A Blázovics 1, M Albert 2, A Sebetény 3, K Szentmihályi 4
  • 1Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
  • 2VetMed Labor Kft., Budapest, Hungary
  • 3London Research Institute, Clare Hall Laboratories, United Kingdom
  • 4Institute of Material and Environmental Chemistry Chemical Research Center Hungarian Academy of Sciences, Budapest, Hungary

Introduction: Cisplatin is a platinum complex widely used as an active anticancer agent in testicular, ovarian and bladder carcinomas, head and neck squamous cell carcinoma, and non-small cell lung cancers. Pt complexes are well-known DNA-alkylating agents and their interaction with proteins may be part of a series of molecular events. Pt compounds can modulate signal transduction routes and induce apoptotic responses. Pt complexes have serious side effects and resistance phenomena.

Aims: Cisplatin is significantly metabolized in the liver and excreted through the kidney but the kidney is also the primary site of Pt accumulation, therefore we were interested in how metal ion homeostasis changes during cisplatin treatment.

Methods: Ten rats were treated with 1% methyl cellulose. Ten animals were injected once i/p with cisplatin (0.65mg/100g body weight) in vehicle. For plasma digestion, 5ml 65% HNO3 and 2ml H2O2. 10ml 65% HNO3 and 5ml H2O2 were applied for liver and kidney samples. The Spectro Genesis ICP-OES equipment was applied with axial plasma observation for measuring element content. Induced free radical reaction measurements were carried out with a Berthold Lumat 9501 luminometer. Sample aliquots were measured in H2O2/.OH-microperoxidase-luminol system.

Results and discussion: Cisplatin treatment decreased K concentration significantly in plasma and increased B, Co, Cr, Fe, Mg, Mn, Ni and Sb concentrations (P<0.05). The presence of Pb in plasma could also be definitely seen. As, Li and V concentrations in all samples were under detection limit. Cisplatin treatment increased Fe concentration significantly in liver and Pt appeared in the organ. It may cause the increase of free radical reactions. At the same time, cisplatin blocked the normal accumulation of Cu and Zn in the kidney and increased Pb, Pt and Sb concentrations. Cisplatin enhanced the free radical level not only in the kidney, but in plasma and liver. Lower Cu and Zn concentrations in the kidney show that the supplement of these elements are vital, because they minimize kidney insufficiency and increase the antioxidant defense system in organs. Support: ETT002/02