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 / 대한신장학회지

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.