Calcium Dobesilate in Prevention and Treatment of Diabetic Retinopathy

Abstract

Diabetic retinopathy is a leading cause of adult vision loss and blindness. Angioprotective drugs are one of possibilities, which can be used in treatment of diabetic retinopathy. Nearly all of them are very efficient antioxidants or reactive oxygen and nitrogen species (RONS) scavengers. They often contain phenolic groups. Most of them are glycosides of plant origin with aglycones of flavonoid structure, i.e. aglycones are polyhydroxylated derivatives of 2phenyl-4H-chromen-2-one or 2-phenyl-4H-1-benzopyran-4-one. Quercetin, which is the aglycone of many glycosides including rutoside, can serve as a typical example. Other glycosides, such as a saponoside escine (Reparil®) isolated from seeds of horse chestnut Aesculus hippocastaneum, have triterpenic aglycones. (In fact, escin is a mixture of several related compounds. The particular structure on the Figure I express escin I that is a mixture of two geometric isomers. They differ in E or Z configuration of 2-methylbut-2-enoyl, which is attached to originally hydroxyl oxygen in position 21 of the triterpenoid scaffold.) (Kim et al., 2004, Carrasco  Vidrio, 2007). Flavonoid glycosides have poor bioavailability that is due to their low lipophilicity. This problem has been solved by etherification of phenolic groups of flavonoid aglycones with hydroxyalkyl such as hydroxyethyl groups (troxerutin) in past (Agolini  Cavallini, 1987, Wadworth  Faulds, 1992) Troxerutin was demonstrated to attenuate neovascularization in retinopathy in streptozocin-induced diabetic rats (Chung et al., 2005). More recently, increased bioavailability of flavonoid glycosides is reached by micronisation without changing their chemical structures. Preparations such as Detralex® or Daflon® contain standardized and micronized flavonoid fraction characterized by its content of diosmin, which is their main active constituent. Their activity in the treatment of diabetic retinopathy was clearly demonstrated (Lacombe et al., 1989). There is nearly only one exception among these quite complex compounds: calcium dobesilate (Danium ®, Doxium ®, Dexium®), which is a very simple synthetic molecule: calcium 2,5dihydroxybenzenesulfonate (see Figure 1)