INHIBITION OF ADVANCED PROTEIN GLYCATION BY 8-QUINOLINECARBOXYLIC HYDRAZIDE

Glycation of proteins is believed to be involved in the pathogenesis o f diabetic complications, and thus the development of potent inhibitor s of protein glycation is highly desirable. We tested the inhibitory e ffects of 12 hydrazide compounds against protein glycation and compare d them with the effects of aminoguanidine (AG), a well-known inhibitor . When bovine serum albumin (BSA) was incubated with 100 mmol/l mannos e for 10 days at 37 degrees C in the presence and absence of hydrazide compounds or AG at 1 mmol/l, only p-anisic hydrazide inhibited Amador i product formation. On the other hand, 8 hydrazides as well as AG inh ibited the formation of advanced glycation end products (AGEs). 8-Quin olinecarboxylic hydrazide (8-QCH), the most potent hydrazide, was more effective than AG. Neither 8-QCH nor AG affected the spontaneous decr ease in Amadori products of preglycated BSA in the absence of sugar, b ut suppressed the spontaneous increase in AGEs from preglycated BSA, w ith higher potency of 8-QCH relative to AG. The results indicate that 8-QCH is a more potent inhibitor of AGE formation than AG and suggest that the inhibition mechanisms of 8-QCH and AG resemble each other.