Analysis by the Carr-Purcell-Meiboom-Gill sequence of the influence of P388 leukemia and of cis-diamminedichloroplatinum(II) nephrotoxicity on water compartmentalization in kidneys and spleens of mice.

Abstract

The multiexponential behavior of the decay curves obtained in vitro by a Carr-Purcell-Meiboom-Gill (CPMG) sequence from spleens and kidneys of mice is analyzed. The mice were inoculated with the acute lymphocytic P388 leukemic cells and treated with the anticancer drug cis-diamminedichloroplatinum(II), cis-Pt. Kidneys and spleens of control animals display four relaxation components. The two longest ones were assigned, in the kidneys, in decreasing order of their relaxation time value, to intracellular and extracellular water, respectively. In spleens, the reversed assignment resulted. The two shortest ones are assigned to different tightly bound hydration water compartments, the fastest relaxing one being more greatly influenced by the unobservable crystalline water. No significant systemic effect on the intra- and extracellular water relaxation times could be observed in the kidneys under P388 leukemia inoculation, despite an apparent increase in the intracellular water content. In contrast, drug administration results in the apparent decrease in or even disappearance of the extracellular water component, with an increase in both relaxation time and apparent fraction of the intracellular water. These effects correlate well with changes in the usual nephrotoxicity parameters and are explained in terms of the well-known cell damage in kidneys under cis-platinum administration. A systemic effect under P388 leukemia disease is observed for the spleen, resulting again in the disappearance of the extracellular water component. The latter is related to splenomegaly due to invasion of the organ by leukemic cells during disease development.