The pyrimido-pyrimidine derivatives, dipyridamole and RA-642, reduce opacification of crystalline lens in diabetic rats.
We assessed the effect of dipyridamole, RA-642 and mopidamol, on lenticular opacities in a model of experimental diabetic cataracts in rats. All three pyrimido-pyrimidine derivatives caused a statistically significant reduction of opacification in crystalline lens as compared with untreated diabetic animals. The production of superoxide anions (phenazine methosulphate [PMS]-induced nitroblue tetrazolium [NBT] reduction) showed a decrease of 81.6%, 78.9% and 1.8% in lens tissue homogenates from rats treated with dipyridamole, RA-642 and mopidamol, respectively. Dipyridamole and RA-642 produced a statistically significant inhibition (50% and 64.8%, respectively) of lipid peroxidation (ferrous sulphate and ascorbic acid [FeAs]-induced malondialdehyde [MDA] production) as compared with the group of untreated diabetic rats. Mopidamol did not exert any inhibitory effect on lipid peroxidation. There was a statistically significant correlation between opacification of lens and PMS-induced NBT reduction and FeAs-induced MDA production. We conclude that the protective effect of dipyridamole and RA-642 from free radical damage to crystalline lens in the model of experimental diabetes used in this study, is the result of the antioxidant action of these compounds. The effect exerted by mopidamol, however, suggest a possible complementary effect of the pyrimido-pyrimidine derivatives through interaction with other mechanisms (e.g., the sorbitol pathway) implicated in the development of cataracts.
de la Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
Moreno
A
A
Mérida
F
F
García-Campos
J
J
Sánchez de la Cuesta
F
F
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002386:Cataract / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004176:Dipyridamole / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009012:Mopidamol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D001786:Blood Glucose; D002316:Cardiotonic Agents; D011743:Pyrimidines; D013481:Superoxides; D009012:Mopidamol; D008315:Malondialdehyde; C010650:RA 642; D004176:Dipyridamole