Changes in Alkaline Phosphatase of Kidney Following Renal Damage with Alloxan

Abstract

Subcut. injns. of a 5% aqueous soln. of alloxan in dosages of 25-600 mg./kg. of white rat produced diabetes and kidney damage. Rats were killed at times varying between 6 and 48 hrs. after injn. and heart''s blood withdrawn immediately for glucose detns. Portions of one kidney were used for chemical analysis of alkaline phosphatase by a modification of the King and Armstrong method. Frozen sections and paraffin sections made from kidney tissue fixed in acetone and absolute alcohol were studied for alkaline phosphatase by Gomori''s method and the azo-dye method of Menten, et al. Kidney tissue fixed in Zenker''s soln. was used for routine sections. Alloxan dosage of 100 mg. or less/kg. produced no symptoms. A dosage of 200-300 mg. gave few symptoms and no decrease in alkaline phosphatase. Twenty-four hrs. after an injn. of 400 mg./kg., the rats were acutely ill and many died. The renal phosphatase was appreciably decreased. Rats receiving 500-600 mg. did not live beyond 28 hrs. and the excised kidney showed a 50% or greater fall in the enzyme. The reduction in renal phosphatase found on chemical analysis paralleled the decrease found histochemically. Lowering of blood sugar by insulin in hyperglycemic rats was not associated with any improvement in renal phosphatase. It is suggested that the damage produced by alloxan is referable to disturbance of certain tissue enzymes.