Korean J Nephrol.  2009 Sep;28(5):397-409.

Effects of Supplementation with a Selective COX-2 Inhibitor and Vitamin C on Glomerular TGF-beta, COX-2, and Antioxidant Activity in Rats with Passive Heymann Nephritis

• Jung YS
• Rim H
• Moon W
• Choi J
• Sol MY

Abstract

PURPOSE
In the passive Heymann nephritis (PHN) rat model of membranous nephropathy, complement induces glomerular epithelial cell injury and proteinuria, which is partially mediated by reactive oxygen species (ROS), TGF-beta, and COX-2. In the current study, we determined the effect of a selective COX-2 inhibitor (celecoxib) and vitamin C on the enzyme system associated with ROS, TGF-beta, and COX-2 in PHN.
METHODS
Four groups of rats with PHN were dosed with polyethylene glycol vehicle (P; n=4), celecoxib (COXi; n=8), vitamin C (VC; n=8), or celecoxib and vitamin C (COXi+VC; n=8) from days 7-21. Each group was then divided into 2 subgroups reflecting the day of the experiment (day-14 and -21 subgroups).
RESULTS
The urine protein was significantly reduced in the VC and COXi+VC groups (subgroup day- 14) compared to the P group (p<0.05). The glomerular TGF-beta expression was reduced in the COXi+ VC group (subgroup day-21) compared to the P group (p<0.05). Glomerular COX-2 expression was increased in the COXi, VC, and COXi+VC groups compared to the P group (p<0.05). The COXi, VC, and COXi+VC groups (subgroup day-21) had decreased activity of lipid peroxide and xanthine oxidase and increased activity of xanthine dehydrogenase, superoxide dismutase, GSH-Px, and catalase. This antioxidant activity was highest in the COXi+VC group (p<0.05).
CONCLUSION
Selective COX-2 inhibitors possess antioxidant effects. The combination of a COX-2 inhibitor and vitamin C was more effective than COX-2 inhibitor or vitamin C alone in increasing antioxidant activity and decreasing TGF-beta.

Keyword

Membranous nephropathy; Antioxidants; Transforming growth factor-beta; Cyclooxygenase 2

MeSH Terms

Animals
Antioxidants
Ascorbic Acid
Catalase
Complement System Proteins
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Epithelial Cells
Glomerulonephritis, Membranous
Polyethylene Glycols
Proteinuria
Pyrazoles
Rats
Reactive Oxygen Species
Sulfonamides
Superoxide Dismutase
Transforming Growth Factor beta
Vitamins
Xanthine Dehydrogenase
Xanthine Oxidase
Antioxidants
Ascorbic Acid
Catalase
Complement System Proteins
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Polyethylene Glycols
Pyrazoles
Reactive Oxygen Species
Sulfonamides
Superoxide Dismutase
Transforming Growth Factor beta
Vitamins
Xanthine Dehydrogenase
Xanthine Oxidase