Inhibition of cataracts in moderately diabetic rats by aminoguanidine.
The effect of aminoguanidine (AG), an inhibitor of advanced glycation, on the development of cataracts was studied in diabetic rats. Rats were made diabetic with streptozotocin, and based on the level of plasma glucose they were grouped as moderately (< 350 mg dl-1 plasma glucose) and severely (> 350 mg dl-1 plasma glucose) diabetic. One half of the animals in each group received AG (25 mg kg-1 body weight each day), intraperitoneally, starting from the day of streptozotocin injection. Progression of lens opacification was recorded using Fundus and Scheimpflug photography at regular time intervals. On the ninetieth day all the rats were killed and the levels of advanced glycation end products (AGE) was determined by measuring the non-tryptophan fluorescence of the lens soluble and insoluble fractions. Densitometric analysis of Scheimpflug images showed that in diabetic rats lens opacification progressed in a biphasic manner, an initial slow progression for the first 60 days, followed by a steep increase during next 30 days. Moderately and severely diabetic rats developed lens opacities more or less at the same time. AGE fluorescence in the lens soluble fractions increased three-fold and seven-fold in the moderately and severely diabetic rats, respectively; whereas in insoluble fractions there was a 30% and three-fold increase in the moderately and severely diabetic rats, respectively. Although AG treatment inhibited the AGE fluorescence of lens soluble and insoluble fractions by about 56% and 75% in moderately diabetic and by 19% and 52% severely diabetic rats, respectively, the development of cataracts was delayed only in the moderately diabetic rats. These results thus suggest that the effect of AG is indeed inhibition of the formation of AGEs. However, in the severely diabetic rats the beneficial effect of AG is overwhelmed by the excessive accumulation of AGEs.
Swamy-Mruthinti
S
S
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912, USA.
Green
K
K
Abraham
E C
EC
D000818:Animals; D002386:Cataract / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D018450:Disease Progression; D017127:Glycation End Products, Advanced / Q000032:analysis; D006146:Guanidines / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000737:chemistry / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine