Effect of protocatechualdehyde on receptor for advanced glycation end products and TGF-beta1 expression in human lens epithelial cells cultured under diabetic conditions and on lens opacity in streptozotocin-diabetic rats.

Abstract

Advanced glycation end products and transforming growth factor-beta (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-beta1 in human lens epithelial cells cultured under diabetic conditions. In addition, the ability of PCA to suppress lens opacification in streptozotocin-diabetic 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-beta1 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.

• Authors: Young Sook Kim, Nan Hee Kim, Sang Won Lee, Yun Mi Lee, Dae Sik Jang, Jin Sook Kim
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 569 Issue 3 Pg. 171-9 (Aug 27 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17597607 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzaldehydes
• Catechols
• Glycation End Products, Advanced
• RNA, Messenger
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Transforming Growth Factor beta1
• advanced glycation end products-bovine serum albumin
• Serum Albumin, Bovine
• protocatechualdehyde
• Streptozocin

Topics

• Administration, Oral
• Animals
• Benzaldehydes (pharmacology)
• Blotting, Western
• Cataract (prevention & control)
• Catechols (pharmacology)
• Cell Line, Transformed
• Diabetes Mellitus, Experimental (complications)
• Gene Expression Regulation (drug effects)
• Glycation End Products, Advanced (antagonists & inhibitors, metabolism)
• Humans
• Lens, Crystalline (cytology, drug effects)
• RNA, Messenger (drug effects, metabolism)
• Rats
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (drug effects, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Salvia miltiorrhiza (chemistry)
• Serum Albumin, Bovine (antagonists & inhibitors, metabolism)
• Streptozocin
• Transforming Growth Factor beta1 (drug effects, metabolism)