Inhibition of diabetes-associated complications by nucleophilic compounds.
Mono- and diaminoguanidine inhibited ambient glucose-induced glycosylated end product formation of albumin and collagen 125I-labeled albumin covalent binding in vitro. Diaminoguanidine was a stronger inhibitor than monoaminoguanidine. These compounds also inhibited rat eye lens aldose reductase activity in vitro noncompetitively with respect to NADPH with Ki = 30.6 mM for monoaminoguanidine and Ki = 12.5 mM for diaminoguanidine. When administered daily for 98 days at a dose of 25 mg/kg body wt i.p., both compounds lowered eye lens sorbitol and aldose reductase activity in normoglycemic and alloxan-induced diabetic rats. Again, diaminoguanidine was a better inhibitor. Daily long-term administration of mono- and diaminoguanidine (25 mg/kg body wt i.p.) inhibited and prevented experimental diabetes-induced lens opacity in rats, respectively. It appears that diaminoguanidine has a better therapeutic potential in controlling diabetic complications.
Kumari
K
K
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
Umar
S
S
Bansal
V
V
Sahib
M K
MK
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003094:Collagen / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism; D000093423:Glycated Serum Albumin
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006146:Guanidines; D012709:Serum Albumin; C022814:glycosylated collagen; C070130:diaminoguanidine; D013012:Sorbitol; D003094:Collagen; D000449:Aldehyde Reductase; C004479:pimagedine; D000093423:Glycated Serum Albumin