Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products.

Abstract Advanced glycation end products( AGEs) not only inhibit DNA synthesisbut also play a role in diabetic retinopathyby evoking apoptosis and inflammation in retinal pericytesvia interaction with a receptor for AGE (RAGE). Similarly, sulforaphane, which is a naturally occurring isothiocyanate that is found in widely consumed cruciferous vegetables, protects against oxidative stress–induced tissue damage. Therefore, we hypothesized that sulforaphanecould inhibit AGE-induced pericytesinjury through its antioxidative properties. Advanced glycation end productstimulated superoxide generation as well as RAGE gene and protein expression in bovine-cultured retinal pericytes, and these effects were prevented by the treatment with sulforaphane. Antibodies directed against RAGE also blocked AGE-evoked reactive oxygen species generation in pericytes. Sulforaphaneand antibodies directed against RAGE significantly inhibited the AGE-induced decrease in DNA synthesis, apoptotic cell death, and up-regulation of monocyte chemoattractant protein 1 messenger RNA levels in pericytes. For the first time, the present study demonstrates that sulforaphanecould inhibit DNA synthesis, apoptotic cell death, and inflammatory reactions in AGE-exposed pericytes, partly by suppressing RAGE expression via its antioxidative properties. Blockade of the AGE-RAGE axis in pericytesby sulforaphanemight be a novel therapeutic target for the treatment of diabetic retinopathy.