Chronotoxicity of nedaplatin in rats

Chronobiol Int. 2004 Jul;21(4-5):601-11. doi: 10.1081/cbi-120039814.

Abstract

Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00h than 08:00h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity*
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Chronotherapy
  • Circadian Rhythm / physiology*
  • Creatinine / metabolism
  • Kidney Cortex / drug effects
  • Kidney Cortex / metabolism
  • Leukocyte Count
  • Male
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / toxicity*
  • Photoperiod
  • Rats
  • Rats, Sprague-Dawley
  • Weight Gain / drug effects

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • nedaplatin
  • Creatinine