ACTA MEDICA PORTUGUnSA 1984; 5: 115-117 ORIGINAL PLACENTAL ALDOSE REDUCTASE INHIBITION BY SILYBIN (preliminary communication) JOAO SANTOS, LOURDES BARREIRA A. MIRA, ANA MARIA FREIRE, MARIA AZEVEDO, CARLOS MANSO Instituto de Quimica Fisiologica. Faculdade de Medicina de Lisboa. Lisboa. Portugal SUMMARY Silybin, a flavonoid obtained from Silymarin is a powerful inhibitor of aldose reductase. It is suggested that it might be beneficial in the therapy and prevention of diabetic complications. RESUMO Inibiçäo da aldose reductase placentária pela silibina. A silibina, urn flavonoide obtido a partir da silirnarina é urn potente inibidor da aldose reductase. Suge re-se que seria interessante experimentar a sua accão terapêutica e preventiva nas cornplicacOes da Diabetes rnellitus. INTRODUCTION Aldose reductase (alditol-NADP oxidoreductase, EC 1.1.1.21) is an enzyme of the polyol pathway, the other being sorbitol dehydrogenase (L-iditol-NAD oxidoreductase, EC 1.1.1.14) which transforms sorbitol in fructose:” 2 aldose reductase sorbitol dehvdrogenasc glucose ~ sorbitol ~ fructose Aldose reductase is not specific for glucose, and accepts as a substract any ose possessing an aldehyde group.3’ ~ Mo re recently it has been demonstrated that aldose reductase is one of the isoenzymes of aldehyde reductase.5 The polyol pathway is especially active in the testis, pla centa, brain, nerve, kidney, lens, pancreatic islets, and is practically absent in other tissues.6 In the red blood cell sor bitol accumulates during incubation with elevated concen trations of glucose, and it has been suggested that the deter mination of sorbitol in the erythrocyte might serve as an in dex of diabetic compensation.7’ 8 The intracellular accumulation of sorbitol in different tissues which possess aldose reductase was held responsible for the development of cataracts, retinopathy, peripheral neuropathy and macrovascular complications.4’ 6 The organs which do not depend on insulin for the trans port of glucose are the most seriously affected, since intra cellular non phosphorylated glucose is metabolized into sor bitol,9 whereas insulin controls free glucose concentration in the other cells, through the activation of its phosphorylat ion. ~ ~‘ In the presence of hyperglycemia, glucose is deviat ed to sorbitol synthesis in the first group of organs. The ac cumulation of sorbitol is responsible for the entry of excess water in the cells and subsequent damage of the tissues.’2 Several inhibitors of aldose reductase have been utilized as an attempt to stop this damage. Sorbinil and Airestatin are powerful inhibitors, but their use in diabetic patients is difficult since they are very toxic.13’ 14, 18 Silybin is a flavonoid which has been employed in the treatment of intoxications due to mushrooms of the Ama nita phalloides type 15, 16 and in the toxic syndrome due to ingestion of rapeseed oil.’7 It is practically nontoxic and may be employed continually for long periods. In the present paper we demonstrate the Silybin is an inhibitor of placental aldose reductase. NADPH NADP NAD NADH 1,lT ~ePN/ Figure 1: Eisenthal plot for determination of Km using DL-glyceraldehyde as substract. Received: December 12, 1983 115