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Effects of Rebamipide in a Model of Experimental Diabetes and on the Synthesis of Transforming Growth Factor-b and Fibronectin, and Lipid Peroxidation Induced by High Glucose in Cultured Mesangial Cells

Authors
 HUNJOO HA  ;  SANG H. LEE  ;  K. HWAN KIM 
Citation
 JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, Vol.281(3) : 1457-1462, 1997 
Journal Title
 JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 
ISSN
 0022-3565 
Issue Date
1997
MeSH
Alanine/analogs & derivatives* ; Alanine/pharmacology ; Animals ; Cells, Cultured ; Diabetes Mellitus, Experimental/drug therapy ; Enzyme Inhibitors/pharmacology* ; Fibronectins/biosynthesis ; Fibronectins/drug effects* ; Glucose/pharmacology* ; Lipid Metabolism* ; Male ; Quinolones/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta/biosynthesis ; Transforming Growth Factor beta/drug effects*
Abstract
Oxidative stress has been proposed as the basis for the pathogenesis of diabetic nephropathy. Rebamipide is a novel antiulcer drug that has, in addition, oxygen radical scavenging activity. Our study examines whether rebamipide could ameliorate the pathophysiology associated with experimental diabetes in vivo, such as microalbuminuria, and to reverse the increased production of transforming growth factor-beta1 and fibronectin in SV-40 transformed murine mesangial cells in culture that were stimulated with high glucose. Chronic administration of rebamipide (100 mg/kg/day, p.o., for 3 wk) to rats, in which diabetes was previously induced by the i.v. injection of streptozotocin 50 mg/kg, reversed hyperglycemia, which would contribute to prevent the increases in urinary excretion rates of albumin and lipid peroxides observed in this experimental model. Rebamipide, at this dose level, did not cause any discernible effect on age-matched control rats. Rebamipide 2 mM was as effective as 20 mM of dimethylthiourea, a known hydroxyl radical scavenger, in inhibiting the increase in lipid peroxides, transforming growth factor-beta1, fibronectin mRNAs and proteins induced by incubation of cultured mesangial cells with high glucose. Our data suggest that rebamipide attenuates high glucose-induced nephropathy, which is attributable, in part, to its antioxidative property and, in part, to its effect on reversing hyperglycemia.
Full Text
http://jpet.aspetjournals.org/content/281/3/1457.long
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/177344
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