Effects of Supplementation with a Selective COX-2 Inhibitor and Vitamin C on Glomerular TGF-β, COX-2, and Antioxidant Activity in Rats with Passive Heymann Nephritis |
Yeon Soon Jung, M.D.1, Hark Rim, M.D.1, Won Moon, M.D.1, Jongwon Choi, Ph.D.2 and Mee Young Sol, M.D.3 |
Departments of Internal Medicine1 Kosin University College of Medicine, Gospel Hospital, Department of Pharmacology2 College of Pharmacy, Kyungsung University, Department of Pathology3 School of Medicine, Pusan National University Hospital, Busan, Korea |
기초연구 : Effects of Supplementation with a Selective COX-2 Inhibitor and Vitamin C on Glomerular TGF-β, COX-2, and Antioxidant Activity in Rats with Passive Heymann Nephritis |
Yeon Soon Jung, M.D.1, Hark Rim, M.D.1, Won Moon, M.D.1, Jongwon Choi, Ph.D.2 and Mee Young Sol, M.D.3 |
Departments of Internal Medicine1, Kosin University College of Medicine, Gospel Hospital, Department of Pharmacology2, College of Pharmacy, Kyungsung University, Department of Pathology3, School of Medicine, Pusan National University Hospital, Busan, Kore |
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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-β, 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-β, 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-β 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-β. |
Key Words:
Membranous nephropathy, Antioxidants, Transforming growth factor-β, Cyclooxygenase 2 |
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