Effects of Celecoxib in Young Rats: Histopathological Changes in Tissues and Alterations of Oxidative Stress/Antioxidant Defense System

다국어 초록 (Multilingual Abstract)

Celecoxib is increasingly being used in children with rheumatologic complaints. Although the particular concerns about the safety of the drug, there are only a small number of published studies in children. This study was performed to investigate the effects of celecoxib on oxidative stress and antioxidant enzyme activities as well as celecoxib-induced changes in liver, kidneys and stomach of young rats. Four weeks-old Wistar albino, female rats were used. Celecoxib was given by gavage for 14 days. Control rats received only vehicle. Blood and organs were taken under pentobarbital anesthesia. Plasma malondialdehyde levels were increased by treatment. Catalase activity was increased, while glutathione peroxidase activity was decreased. Superoxide dismutase and glucose-6-phosphate dehydrogenase activities was not changed by treatment. The reduced glutathione content of kidneys were higher, while there was no significant difference in liver content, as compared with controls. Significant changes were observed in serum parameters of rats treated with celecoxib. Histopathological evaluation of organs was done by an experienced pathologist unaware of the treatment. Results of the present study indicated the alterations of oxidant/antioxidant status and histopathological changes in tissues of young rats treated with celecoxib.

참고문헌 (Reference)

1 Tanaka, A., "Up-regulation of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage" 300 : 754-761, 2002

2 Misra, H. P., "The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase" 25 : 3170-3175, 1972

3 Orhan, H., "The in vitro effects of new non-steroidal antiinflammatory compounds on antioxidant system of human erythrocytes" 51 : 397-402, 1999

4 Wallace, J. L., "The 1994 Merck Frosst. Award. Mechanisms of nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal damage-potential for development of gastrointestinal tract safe NSAIDs" 72 : 1493-1498, 1994

5 Stempak, D., "Single-dose and steady-state pharmacokinetics of celecoxib in children" 72 : 490-497, 2002

6 Satoh, K., "Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method" 90 : 37-43, 1978

7 Rosai, J., "Rosai and Ackerman's Surgical Pathology" Mosby 648-711, 2004

8 Turner, S., "Role of the selective cyclo-oxygenase- 2 (COX-2) inhibitors in children" 89 : ep46-ep49, 2004

9 Gupta, S., "Role of oxidative stress in celecoxib-induced renal damage in wistar rats" 52 : 3092-3098, 2007

10 Yan, B., "Rofecoxib-induced hepatotoxicity: a forgotten complication of the coxibs" 20 : 351-355, 2006

11 Ahmad, S. R., "Renal failure associated with the use of celecoxib and rofecoxib" 25 : 537-544, 2002

12 Brater, D. C., "Renal effects of Cyclooxygenase-2 selective inhibitors" 23 : S15-S20, 2002

13 Provost, J. P., "Plasma triglycerides: an overlooked biomarker of hepatotoxicity in the rat" 12 : 95-101, 2003

14 Paulson, S. K., "Pharmacokinetics, tissue distribution, metabolism, and excretion of celecoxib in rats" 28 : 514-521, 2000

15 Tan, H. H., "Nimesulide- induced hepatotoxicity and fatal hepatic failure" 48 : 582-585, 2007

16 Vane, J. R., "Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs" 23 : 232-235, 1971

17 Ferraz, J. G., "Induction of cyclooxygenase 1 and 2 in the rat stomach during endotoxemia: role in resistance to damage" 113 : 195-204, 1997

18 Vane, J. R., "Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation" 15 : 2046-2050, 1994

19 De Ferreyra, E. C., "Increased glutathione (GSH) content in livers of control and carbon tetrachloride poisoned rats treated with the anticalmodulin drug trifluoperazine (TFP)" 53 : 399-402, 1986

20 Burak Cimen, M. Y., "In vivo effects of meloxicam, celecoxib, and ibuprofen on free radical metabolism in human erythrocytes" 26 : 169-176, 2003

21 Kirkova, M., "In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems. Comparison with non-selective and COX-2 selective NSAIDs" 27 : 99-104, 2007

22 Ozgocmen, S., "In vivo effect of celecoxib and tenoxicam on oxidant/anti-oxidant status of patients with knee osteoarthritis" 35 : 137-143, 2005

23 Hao, C. M., "Hypertension and cyclooxygenase-2 inhibitors: target the renal medulla" 106 : 973-982, 2000

24 Meister, A., "Glutathione and related gammaglutamyl compounds: biosynthesis and utilization" 45 : 559-604, 1976

25 Chakraborty, S., "Exploring effects of different nonsteroidal antiinflammatory drugs on malondialdehyde profile" 63 : 83-88, 2006

26 Sheth, N., "Essentials for starting a pediatric clinical study (4): Clinical pediatric safety planning based on preclinical toxicity studies and pediatric pharmacovigilance guidance" 34 (34): SP327-SP329, 2009

27 Demircan, B., "Effects of indomethacin, celecoxib and meloxicam on glutathione, malondialdehyde and myeloperoxidase in rat gastric tissue" 4 : 383-388, 2005

28 Gambero, A., "Effect of different cyclooxygenase inhibitors on gastric adaptive cytoprotection induced by 20% ethanol" 52 : 425-433, 2007

29 Arai, I., "Effect of NS-398, a new nonsteroidal anti-inflammatory agent, on gastric ulceration and acid secretion in rats" 81 : 259-270, 1993

30 Lie, H. K., "Early experience with the use of celecoxib in a child and adolescent population" 32 : 27-31, 2002

31 Ozaki, N., "Differential regulation of prostacyclin and thromboxane by dexamethasone and celecoxib during oxidative stress in newborn rabbits" 70 : 61-78, 2002

32 Pleban, P. A., "Determination of selenium concentration and glutathione peroxidase activity in plasma and erythrocytes" 28 : 311-316, 1982

33 Morales, E., "Cyclooxygenase-2 inhibitor- associated acute renal failure: case report with rofecoxib and review of the literature" 22 : 1317-1321, 2002

34 Lu, S., "Cyclooxygenase-2 inhibitor celecoxib inhibits promotion of mammary tumorigenesis in rats fed a high fat diet rich in n-6 polyunsaturated fatty acids" 8 : 12-, 2002

35 Zhang, M. Z., "Cyclooxygenase-2 in rat nephron development" 273 : F994-F1002, 1997

36 Ozaki, N. K., "Comparative effects of dexamethasone and celecoxib on growth in newborn rabbits exposed to hyperoxia/normoxia" 49 : 298A-, 2001

37 Kargman, S., "Characterization of Prostaglandin G/H Synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts" 111 : 445-454, 1996

38 Chang, H., "Celecoxib stimulates reparatory burst through pertussis toxin-sensitive Gprotein, a possible signal for beta 2-integrin expression on human neutrophils" 484 : 29-39, 2004

39 Liu, H., "Celecoxib exacerbates hepatic fibrosis and induces hepatocellular necrosis in rats treated with porcine serum" 88 : 63-67, 2009

40 Aebi, H., "Catalase in vitro" 105 : 121-126, 1984

41 Crofford, L. J., "COX-1 and COX-2 tissue expression: implication and prediction" 49 : 15-19, 1997

42 Tietz, N. W., "Biochemical Aspects of Hematology, in Fundamentals of Clinical Chemistry" W.B. Saunders Co 803-805, 1987

43 Yagi, K., "Assay for blood plasma or serum" 105 : 328-331, 1984

44 Papaioannides, D., "Acute renal dysfunction associated with selective COX-2 inhibitor therapy" 33 : 609-611, 2001

45 Foeldvari, I., "A prospective study comparing celecoxib with naproxen in children with juvenile rheumatoid arthritis" 36 : 174-182, 2009

46 Stempak, D., "A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors" 28 : 720-728, 2006