Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice

Görkem Kısmalı; Aykut Göktürk Üner; Öğünç Meral; Merve Alpay; Berrin Salmanoğlu; Dilek Ülker Çakır; Funda Kosova; Tevhide Sel

doi:10.33988/auvfd.521040

Research Article

Year 2019, , 351 - 356, 09.09.2019

Görkem Kısmalı Aykut Göktürk Üner Öğünç Meral , Merve Alpay , Berrin Salmanoğlu , Dilek Ülker Çakır Funda Kosova , Tevhide Sel

https://doi.org/10.33988/auvfd.521040

Abstract

References

1. Aggarwal B, Prasad S, Sung B, et al (2013): Prevention and treatment of colorectal cancer by natural agents from mother nature. Curr Colorectal Cancer Rep, 9, 37-56.
2. Alagozlu H, Gorgul A, Bilgihan A, et al (2013): Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis. Clin Res Hepatol Gastroenterol, 37, 80-85.
3. Ashokkumar P, Sudhandiran G (2008): Protective role of luteolin on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis. Biomed Pharmacother, 62, 590-597.
4. Baliga MS, Wang H, Zhuo P, et al (2007): Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage. Biol Trace Elem Res, 115, 227-242.
5. Brigelius-Flohé R, Kipp A (2009): Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta, 1790, 1555-1568.
6. Cerutti P, Ghosh R, Oya Y, et al (1994): The role of the cellular antioxidant defense in oxidant carcinogenesis. Environ Health Perspect, 102, 123-129.
7. Das U (2002): A radical approach to cancer. Med Sci Monit, 4, 79-92.
8. Davies MJ, Fu S, Wang H, et al (1999): Stable markers of oxidant damage to proteins and their application in the study of human disease. Free Radic Biol Med, 11-12, 1151-1163.
9. Del Tacca M, Colucci R, Fornai M, et al (2002): Efficacy and tolerability of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug. Clin Drug Investig, 22, 799-818.
10. Diwadkar-Navsariwala V, Prins GS, Swanson SM, et al (2006): Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model. Proc Natl Acad Sci USA, 103, 8179-8184.
11. Fajardo AM, Piazza GA (2015): Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention. Am J Physiol Gastrointest Liver Physiol, 309, 59-70.
12. Hansen RD, Krath BN, Frederiksen K, et al (2009): GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutat Res, 664, 13-19.
13. Haug U, Poole EM, Xiao L, et al (2012): Glutathione peroxidase tagSNPs: associations with rectal cancer but not with colon cancer. Genes Chromosomes Cancer, 51, 598-605.
14. Heirman I, Ginneberge D, Brigelius-Flohé R, et al (2006): Blocking tumor cell eicosanoid synthesis by GP x 4 impedes tumor growth and malignancy. Free Radic Biol Med, 40, 285-294.
15. Hwang D, Scollard D, Byrne J, et al (1998): Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst, 90, 455-460.
16. Johnson JJ, Mukhtar H (2007): Curcumin for chemoprevention of colon cancer. Cancer Lett, 255, 170-181.
17. Khan AM, Rampal S (2014): Effects of repeated oral administration of pazufloxacin mesylate and meloxicam on the antioxidant status in rabbits. J Am Assoc Lab Anim Sci, 53, 399-403. 18. Kim JH, Hue JJ, Kang BS, et al (2011): Effects of selenium on colon carcinogenesis induced by azoxymethane and dextran sodium sulfate in mouse model with high-iron diet. Lab Anim Res, 27, 9-18.
19. Kochi T, Shimizu M, Shirakami Y, et al (2015): Utility of Apc-mutant rats with a colitis-associated colon carcinogenesis model for chemoprevention studies. Eur J Cancer Prev, 24, 180-187.
20. Kraus S, Naumov I, Arber N (2013): COX-2 active agents in the chemoprevention of colorectal cancer. Recent Results Cancer Res, 191, 95-103.
21. Kuper H, Adami HO, Trichopoulos D (2000): Infections as a major preventable cause of human cancer. J Intern Med, 248, 171-183.
22. Lee SM, Kim N, Son HJ, et al (2016): The effect of sex on the azoxymethane/dextran sulfate sodium-treated mice model of colon cancer. J Cancer Prev, 21, 271-278.
23. Maier TJ, Schilling K, Schmidt R, et al (2004): Cyclooxygenase-2 (COX-2)-dependent and -independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. Biochem Pharmacol, 67, 1469-1478.
24. Meira LB, Bugni JM, Green SL, et al (2008): DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest, 118, 2516-2525.
25. Nakanishi M, Rosenberg DW (2013): Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol, 35, 123-137.
26. O'Banion MK (1999): Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Crit Rev Neurobiol, 13, 45-82.
27. Ohshima H, Bartsch H (1994): Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res, 305, 253-264.
28. Paglia DE, Valentine WN (1967): Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med, 70, 158-169.
29. Pandurangan AK, Ismail S, Saadatdoust Z, et al (2015): Allicin alleviates dextran Sodium sulfate- (DSS-) induced ulcerative colitis in BALB/c mice. Oxid Med Cell Longev, 2015, 1-13.
30. Renuka, Kumar S, Sharma B, et al (2015): n-3 PUFAs: an elixir in prevention of colorectal cancer. Curr Colorectal Cancer Rep, 11, 141-149.
31. Reuter S, Gupta SC, Chaturvedi MM, et al (2010): Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med, 49, 1603-1616.
32. Sohn OS, Ishizaki H, Yang CS, et al (1991): Metabolism of azoxymethane, methylazoxymethanol and N-nitrosodimethylamine by cytochrome P450IIE1. Carcinogenesis, 12, 127-131.
33. Tan BL, Norhaizan ME, Huynh K, et al (2015): Brewers' rice modulates oxidative stress in azoxymethane-mediated colon carcinogenesis in rats. World J Gastroenterol, 21, 8826-8835.
34. Thaker AI, Shaker A, Rao MS, et al (2012): Modeling colitis-associated cancer with azoxymethane (AOM) and dextran sulfate sodium (DSS). J Vis Exp, 67, e4100.
35. Thirupurasundari CJ, Padmini R, Devaraj SN (2009): Effect of berberine on the antioxidant status, ultrastructural modifications and protein bound carbohydrates in azoxymethane-induced colon cancer in rats. Chem Biol Interact, 177, 190-195.
36. Toppo S, Flohé L, Ursini F, et al (2009): Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme. Biochim Biophys Acta, 1790, 1486-1500.
37. Tüzün A, Erdil A, Inal V, et al (2002): Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease. Clin Biochem, 35, 569-572.
38. Wang D, Dubois RN (2006): Prostaglandins and cancer. Gut, 55, 115-122.
39. Watkins DN, Lenzo JC, Segal A, et al (1999): Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer. Eur Respir J, 14, 412-418.
40. Witko-Sarsat V, Gausson V, Nguyen AT, et al (2003): AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for N-acetylcysteine treatment in dialysis patients. Kidney Int, 64, 82-91.
41. Yoshimi K, Tanaka T, Takizawa A, et al (2009): Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat. Cancer Sci, 100, 2022-2027.
42. Yoshioka T, Kawada K, Shimada T, et al (1979): Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol, 135, 372-376.
43. Yu C, Wen XD, Zhang Z, et al (2015): American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice. J Ginseng Res, 39, 14-21.
44. Zhang L, Yu J, Park BH, et al (2000): Role of BAX in the apoptotic response to anticancer agents. Science, 290, 989-992.
45. Zhu H, Li YR (2012): Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood), 237, 474-80.

Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice

Year 2019, , 351 - 356, 09.09.2019

Görkem Kısmalı Aykut Göktürk Üner Öğünç Meral , Merve Alpay , Berrin Salmanoğlu , Dilek Ülker Çakır Funda Kosova , Tevhide Sel

https://doi.org/10.33988/auvfd.521040

Abstract

Natural products and
anti-inflammatory agents including cyclooxygenase-2 (COX-2) inhibitors which is
a type of nonsteroidal anti-inflammatory drugs (NSAIDs) are highly considerable
interest for the prevention of carcinogenesis. The objective of this study is
to evaluate the oxidative status of colitis-associated cancer induced by azoxymethane
(AOM)/dextran sulfate sodium (DSS), and the effects of COX-2 inhibitor in mice.
Totally 40 mice were randomized and divided to four groups. All animals except
control and Cox-2 inhibitor alone group received AOM/DSS to establish
colitis-associated cancer model as reported elsewhere. COX-2 preferential
inhibitor meloxicam was used to minimize side effects such as gastrointestinal
hemorrhage. Meloxicam were used (5mg/kg, intraperitoneal) three times a week
with meloxicam alone and AOM/DSS + meloxicam group. Superoxide dismutase (SOD),
Glutathione peroxidase (GPx), Malondialdehyde (MDA) and Advanced Oxidation
Protein Products (AOPP) which all of them are oxidative stress markers were
measured by spectrophotometrically. The combination treatment of Meloxicam and
AOM/DSS significantly increased (P< 0.05) SOD activities in mice. GPx
activities were found significantly increased (P< 0.05) in Meloxicam and
AOM/DSS combinations or alone. There were no differences between the control
and treatment groups of MDA levels. AOPP levels of Meloxicam and AOM/DSS
combination group were found higher than the other groups. Meloxicam and /or
AOM/DSS treatment not caused lipid peroxidations, but increased the antioxidant
enzymes and Advanced Oxidation Protein Products levels.

Keywords

Azoxymethane, colon cancer, COX-2, dextran sulfate sodium, oxidative stress

References

1. Aggarwal B, Prasad S, Sung B, et al (2013): Prevention and treatment of colorectal cancer by natural agents from mother nature. Curr Colorectal Cancer Rep, 9, 37-56.
2. Alagozlu H, Gorgul A, Bilgihan A, et al (2013): Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis. Clin Res Hepatol Gastroenterol, 37, 80-85.
3. Ashokkumar P, Sudhandiran G (2008): Protective role of luteolin on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis. Biomed Pharmacother, 62, 590-597.
4. Baliga MS, Wang H, Zhuo P, et al (2007): Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage. Biol Trace Elem Res, 115, 227-242.
5. Brigelius-Flohé R, Kipp A (2009): Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta, 1790, 1555-1568.
6. Cerutti P, Ghosh R, Oya Y, et al (1994): The role of the cellular antioxidant defense in oxidant carcinogenesis. Environ Health Perspect, 102, 123-129.
7. Das U (2002): A radical approach to cancer. Med Sci Monit, 4, 79-92.
8. Davies MJ, Fu S, Wang H, et al (1999): Stable markers of oxidant damage to proteins and their application in the study of human disease. Free Radic Biol Med, 11-12, 1151-1163.
9. Del Tacca M, Colucci R, Fornai M, et al (2002): Efficacy and tolerability of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug. Clin Drug Investig, 22, 799-818.
10. Diwadkar-Navsariwala V, Prins GS, Swanson SM, et al (2006): Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model. Proc Natl Acad Sci USA, 103, 8179-8184.
11. Fajardo AM, Piazza GA (2015): Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention. Am J Physiol Gastrointest Liver Physiol, 309, 59-70.
12. Hansen RD, Krath BN, Frederiksen K, et al (2009): GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutat Res, 664, 13-19.
13. Haug U, Poole EM, Xiao L, et al (2012): Glutathione peroxidase tagSNPs: associations with rectal cancer but not with colon cancer. Genes Chromosomes Cancer, 51, 598-605.
14. Heirman I, Ginneberge D, Brigelius-Flohé R, et al (2006): Blocking tumor cell eicosanoid synthesis by GP x 4 impedes tumor growth and malignancy. Free Radic Biol Med, 40, 285-294.
15. Hwang D, Scollard D, Byrne J, et al (1998): Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst, 90, 455-460.
16. Johnson JJ, Mukhtar H (2007): Curcumin for chemoprevention of colon cancer. Cancer Lett, 255, 170-181.
17. Khan AM, Rampal S (2014): Effects of repeated oral administration of pazufloxacin mesylate and meloxicam on the antioxidant status in rabbits. J Am Assoc Lab Anim Sci, 53, 399-403. 18. Kim JH, Hue JJ, Kang BS, et al (2011): Effects of selenium on colon carcinogenesis induced by azoxymethane and dextran sodium sulfate in mouse model with high-iron diet. Lab Anim Res, 27, 9-18.
19. Kochi T, Shimizu M, Shirakami Y, et al (2015): Utility of Apc-mutant rats with a colitis-associated colon carcinogenesis model for chemoprevention studies. Eur J Cancer Prev, 24, 180-187.
20. Kraus S, Naumov I, Arber N (2013): COX-2 active agents in the chemoprevention of colorectal cancer. Recent Results Cancer Res, 191, 95-103.
21. Kuper H, Adami HO, Trichopoulos D (2000): Infections as a major preventable cause of human cancer. J Intern Med, 248, 171-183.
22. Lee SM, Kim N, Son HJ, et al (2016): The effect of sex on the azoxymethane/dextran sulfate sodium-treated mice model of colon cancer. J Cancer Prev, 21, 271-278.
23. Maier TJ, Schilling K, Schmidt R, et al (2004): Cyclooxygenase-2 (COX-2)-dependent and -independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. Biochem Pharmacol, 67, 1469-1478.
24. Meira LB, Bugni JM, Green SL, et al (2008): DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest, 118, 2516-2525.
25. Nakanishi M, Rosenberg DW (2013): Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol, 35, 123-137.
26. O'Banion MK (1999): Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Crit Rev Neurobiol, 13, 45-82.
27. Ohshima H, Bartsch H (1994): Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res, 305, 253-264.
28. Paglia DE, Valentine WN (1967): Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med, 70, 158-169.
29. Pandurangan AK, Ismail S, Saadatdoust Z, et al (2015): Allicin alleviates dextran Sodium sulfate- (DSS-) induced ulcerative colitis in BALB/c mice. Oxid Med Cell Longev, 2015, 1-13.
30. Renuka, Kumar S, Sharma B, et al (2015): n-3 PUFAs: an elixir in prevention of colorectal cancer. Curr Colorectal Cancer Rep, 11, 141-149.
31. Reuter S, Gupta SC, Chaturvedi MM, et al (2010): Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med, 49, 1603-1616.
32. Sohn OS, Ishizaki H, Yang CS, et al (1991): Metabolism of azoxymethane, methylazoxymethanol and N-nitrosodimethylamine by cytochrome P450IIE1. Carcinogenesis, 12, 127-131.
33. Tan BL, Norhaizan ME, Huynh K, et al (2015): Brewers' rice modulates oxidative stress in azoxymethane-mediated colon carcinogenesis in rats. World J Gastroenterol, 21, 8826-8835.
34. Thaker AI, Shaker A, Rao MS, et al (2012): Modeling colitis-associated cancer with azoxymethane (AOM) and dextran sulfate sodium (DSS). J Vis Exp, 67, e4100.
35. Thirupurasundari CJ, Padmini R, Devaraj SN (2009): Effect of berberine on the antioxidant status, ultrastructural modifications and protein bound carbohydrates in azoxymethane-induced colon cancer in rats. Chem Biol Interact, 177, 190-195.
36. Toppo S, Flohé L, Ursini F, et al (2009): Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme. Biochim Biophys Acta, 1790, 1486-1500.
37. Tüzün A, Erdil A, Inal V, et al (2002): Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease. Clin Biochem, 35, 569-572.
38. Wang D, Dubois RN (2006): Prostaglandins and cancer. Gut, 55, 115-122.
39. Watkins DN, Lenzo JC, Segal A, et al (1999): Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer. Eur Respir J, 14, 412-418.
40. Witko-Sarsat V, Gausson V, Nguyen AT, et al (2003): AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for N-acetylcysteine treatment in dialysis patients. Kidney Int, 64, 82-91.
41. Yoshimi K, Tanaka T, Takizawa A, et al (2009): Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat. Cancer Sci, 100, 2022-2027.
42. Yoshioka T, Kawada K, Shimada T, et al (1979): Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol, 135, 372-376.
43. Yu C, Wen XD, Zhang Z, et al (2015): American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice. J Ginseng Res, 39, 14-21.
44. Zhang L, Yu J, Park BH, et al (2000): Role of BAX in the apoptotic response to anticancer agents. Science, 290, 989-992.
45. Zhu H, Li YR (2012): Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood), 237, 474-80.

There are 44 citations in total.

Details

Primary Language	English
Subjects	Veterinary Surgery
Journal Section	Articles
Authors	Görkem Kısmalı 0000-0003-3414-4697 Aykut Göktürk Üner 0000-0002-9242-8279 Öğünç Meral 0000-0001-8813-4991 Merve Alpay 0000-0002-8782-9561 Berrin Salmanoğlu 0000-0003-4344-5782 Dilek Ülker Çakır 0000-0002-8796-6363 Funda Kosova 0000-0001-8070-5067 Tevhide Sel
Publication Date	September 9, 2019
Published in Issue	Year 2019

Cite

APA	Kısmalı, G., Üner, A. G., Meral, Ö., Alpay, M., et al. (2019). Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 66(4), 351-356. https://doi.org/10.33988/auvfd.521040
AMA	Kısmalı G, Üner AG, Meral Ö, Alpay M, Salmanoğlu B, Ülker Çakır D, Kosova F, Sel T. Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice. Ankara Univ Vet Fak Derg. September 2019;66(4):351-356. doi:10.33988/auvfd.521040
Chicago	Kısmalı, Görkem, Aykut Göktürk Üner, Öğünç Meral, Merve Alpay, Berrin Salmanoğlu, Dilek Ülker Çakır, Funda Kosova, and Tevhide Sel. “Oxidative Status of Colitis-Associated Cancer Model Induced by Azoxymethane /Dextran Sulfate Sodium and the Effects of COX-2 Inhibitor in Mice”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 66, no. 4 (September 2019): 351-56. https://doi.org/10.33988/auvfd.521040.
EndNote	Kısmalı G, Üner AG, Meral Ö, Alpay M, Salmanoğlu B, Ülker Çakır D, Kosova F, Sel T (September 1, 2019) Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice. Ankara Üniversitesi Veteriner Fakültesi Dergisi 66 4 351–356.
IEEE	G. Kısmalı, A. G. Üner, Ö. Meral, M. Alpay, B. Salmanoğlu, D. Ülker Çakır, F. Kosova, and T. Sel, “Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice”, Ankara Univ Vet Fak Derg, vol. 66, no. 4, pp. 351–356, 2019, doi: 10.33988/auvfd.521040.
ISNAD	Kısmalı, Görkem et al. “Oxidative Status of Colitis-Associated Cancer Model Induced by Azoxymethane /Dextran Sulfate Sodium and the Effects of COX-2 Inhibitor in Mice”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 66/4 (September 2019), 351-356. https://doi.org/10.33988/auvfd.521040.
JAMA	Kısmalı G, Üner AG, Meral Ö, Alpay M, Salmanoğlu B, Ülker Çakır D, Kosova F, Sel T. Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice. Ankara Univ Vet Fak Derg. 2019;66:351–356.
MLA	Kısmalı, Görkem et al. “Oxidative Status of Colitis-Associated Cancer Model Induced by Azoxymethane /Dextran Sulfate Sodium and the Effects of COX-2 Inhibitor in Mice”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, vol. 66, no. 4, 2019, pp. 351-6, doi:10.33988/auvfd.521040.
Vancouver	Kısmalı G, Üner AG, Meral Ö, Alpay M, Salmanoğlu B, Ülker Çakır D, Kosova F, Sel T. Oxidative status of colitis-associated cancer model induced by azoxymethane /dextran sulfate sodium and the effects of COX-2 inhibitor in mice. Ankara Univ Vet Fak Derg. 2019;66(4):351-6.

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