Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 569, Issue 3, Pages 171-179Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2007.05.054
Keywords
diabetic complication; protocatechualdehyde; advanced glycation end product; Receptor for advanced glycation end products; TGF-beta; lens opacity
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Advanced glycation end products and transforming growth factor-l (TGF-beta) have been implicated in the development of diabetic complications such as cataract. The diverse metabolic effects of protocatechualdehyde (PCA, 3, 4-dihydroxybenzaldehyde) include the inhibition of aldose reductase and oxidation, two processes that are involved in the development of complications in diabetic patients. Here, the potential therapeutic effects of PCA in the treatment of diabetic complications were studied by determining this compound's ability to inhibit the formation of advanced glycation end products-bovine serum albumin (BSA) and the expression of receptor for advanced glycation end products and TGF-beta 1 in human lens epithelial cells cultured under diabetic conditions. In addition, the ability of PCA to suppress lens opacification in streptozotocindiabetic rats was analyzed. PCA significantly reduced advanced glycation end products-BSA formation in vitro and was more effective than aminoguanidine. In human lens epithelial cells, PCA significantly inhibited the induction of receptor for advanced glycation end products protein and mRNA expression by the receptor for advanced glycation end products-specific ligand S100b. Moreover, PCA inhibited high glucose- or S100b-induced TGF-beta 1 protein and mRNA expression as well as nuclear accumulation of phosphorylated Smad2/3. In streptozotocin-induced diabetic cataract in rats, oral administration of PCA (25 mg/kg body weight) for 8 weeks significantly ameliorated the development of lens opacity (cataract) with effect on glycemic control. These results suggest that PCA is of therapeutic interest with respect to the prevention of diabetic complications such as diabetic cataract. 0 2007 Elsevier B.V. All rights reserved.
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