INTERACTION OF AZATHIOPRINE AND GLUTATHIONE IN LIVER OF RAT

  • 1 January 1977
    • journal article
    • research article
    • Vol. 200  (3) , 479-486
Abstract
Azathioprine [an immunosuppressive agent] was administered to rats to study its interaction with glutathione in vivo. Glutathione levels were measured sequentially in liver, red blood cells, kidney and small intestine after i.p. injections of azathioprine (6.25-100 .mu.mol/100 g body wt). Five minutes after drug administration, dose-related selective depletion of hepatic glutathione up to 50% of control was observed. By 60 min, 80% depletion of hepatic glutathione was observed. Red cell glutathione depletion was also observed but lagged behind hepatic changes. Five minutes after azathioprine administrations, no change in red cell glutathione was seen with all doses of azathioprine, but a dose-related increase in plasma 6-mercaptopurine and azathioprine was observed. At all azathioprine doses and at all time intervals after drug administration, the hepatic contribution to total glutathione consumption predominated. No change in glutathione levels in kidney or small intestine was observed after azathioprine. Thus, the liver plays a major role in the metabolism of azathioprine through the interaction of the drug with glutathione.

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