Inhibition of advanced protein glycation by 8-quinolinecarboxylic hydrazide.
Glycation of proteins is belived to be involved in the pathogenesis of diabetic complications, and thus the development of potent inhibitors of protein glycation is highly desirable. We tested the inhibitory effects of 12 hydrazide compounds against protein glycation and compared them with the effects of aminoguanidine (AG), a well-known inhibitor. When bovine serum albumin (BSA) was incubated with 100 mmol/l mannose 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 Amadori product formation. On the other hand, 8 hydrazides as well as AG inhibited the formation of advanced glycation end products (AGEs). 8-Quinolinecarboxylic hydrazide (8-QCH), the most potent hydrazide, was more effective than AG. Neither 8-QCH nor AG affected the spontaneous decrease in Amadori products of preglycated BSA in the absence of sugar, but suppressed the spontaneous increase in AGEs from preglycated BSA, with 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.
Miwa
I
I
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Tsugawa
T
T
Koyasu
K
K
Terada
Y
Y
D006023:Glycoproteins / Q000138:chemical synthesis*; D006146:Guanidines / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013268:Stimulation, Chemical
D006023:Glycoproteins; D006146:Guanidines; D012710:Serum Albumin, Bovine; C004479:pimagedine