Expression of VEGF-A And COX-2 mRNA in non-steroidal anti-inflammatory drugs treated rat primary colonic fibroblast
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) is often used to shorten recovery time after surgery, including after colon anastomosis surgery. Studies showed that NSAIDs might involve in the development of colon anastomotic leakage. However, the effect of NSAIDs in colon anastomosis leakage is still a subject of controversy. Studies indicated that selectivity of COX-2 might have a role in the deleterious effect of NSAIDs in colon anastomosis. Disruption of VEGF-A by NSAIDs also suspected to be the culprit in the development of anastomosis leakage during NSAIDs treatment. This study aimed to investigate the NSAIDs effect toward VEGF-A and COX-2 mRNA in rat primary colonic fibroblast. The in vitro study was conducted using fibroblast isolated from rat colon. The isolated fibroblast was divided into 4 groups of treatment i.e.controlgroup, acetaminophen group, metamizole group, and ketorolacgroup. After 48 h of treatment, the cell was harvested and the RNA was isolated. The expression of VEGF-A and COX-2 mRNA was conducted using semi-quantitative PCR(sq-PCR). Both VEGF-A and COX-2 were not expressed in untreated rat colon fibroblast. However, VEGF-A mRNA washighly expressed in the ketorolacgroup. Interestingly, COX-2 mRNA couldbe seen in the ketorolac and metamizole groups but not in the acetaminophen group. The COX-2 mRNA expression wasthe highest in ketorolac treated rat colon fibroblast. It can be concluded that the effect of various kinds of NSAIDs towards VEGF-A and COX-2 mRNA expression of colon fibroblasts is different. This condition is duetotheir different inhibitory selectivity towards COX-1 and COX2.
References
Garimella V, Cellini C. Postoperative pain control. Clin Colon Surg 2013; 26(3):191-6.
https://doi.org/10.1055/s-0033-1351138
Li Z, Wang W, Wang X, Jiang L, Wang F,Liu Q. A sustained released mixture of vascular endothelial growth factor 165 and fibrin glue strengthens healing of ileal anastomoses in a rabbit model with intraperitoneal infection. Ann Surg Treat Res 2017; 93(3):159-65.
https://doi.org/10.4174/astr.2017.93.3.159
Ji C, Xiong Y, Pan X, Guo X, Li Z, Qian S, et al. Effect of non-steroidal anti-inflammatory drugs on increasing the incidence of colonic anastomosis in rats. Int J Clin Exp Pathol 2015; 8(6):6126-34.
Hakkarainen TW, Steele SR, Bastaworous A, Dellinger EP, Farrokhi E, Farjah F et al. Nonsteroidal anti-inflammatory drugs and the risk for anastomotic failure: a report from Washington State’s Surgical Care and Outcomes Assessment Program (SCOAP). JAMA Surg 2015; 150(3):223-8.
https://doi.org/10.1001/jamasurg.2014.2239
Thalia GE. Studi in vitro pengaruh anti inflamasinon-steroid terhadap proliferasi kultur fibroblast kolontikus [Dissertation]. Yogyakarta: Faculty of Medicine, Universitas Gadjah Mada, 2017.
Syk I, Mirastschijski U, Jeppsson BW, Agren MS. Experimental colonic obstruction increases collagen degradation by matrix metalloproteinases in the bowel wall. Dis Colon Rectum 2003; 46(9):1251-9.
https://doi.org/10.1007/s10350-004-6723-x
Jones MK, Wang H, Peskar BM, Levin E, Itani RM, Sarfeh IJ, et al. Inhibition of angiogenesis by non-steroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 1999; 5(24):1418–23.
Eming S, Krieg T. Molecular mechanisms of VEGF-A action during tissue repair. J Investig Dermatol Symp Proc 2006; 11(1):79-86.
https://doi.org/10.1038/sj.jidsymp.5650016
Pages G, Pouyssegur J. Transcriptional regulation of the vascular endothelial growth factor gene? a concert of activating factors. Cardiovasc Res 2005; 65(3):564-73.
https://doi.org/10.1016/j.cardiores.2004.09.032
Minchenko A, Bauer T, Salceda S, Caro J. Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab invest 1994; 71(3):374-9.
Crofford LJ. COX-1 and COX-2 tissue expression: implications and predictions. J Rheumatol Suppl 1997; 49:15-9.
Tanaka A, Araki H, Hase S, Komoike Y, Takeuchi K. Upregulation of COX-2 by inhibition of COX-1 in the rat: a key to NSAID-induced gastric injury. Aliment Pharmacol Ther 2002; 16(Suppl 2):90-101.
https://doi.org/10.1046/j.1365-2036.16.s2.22.x
Singh S, Graff LA, Bernstein CN. Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Am J Gastroenterol 2009; 104(5):1298-313.
https://doi.org/10.1038/ajg.2009.15
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 2008; 22(2):383-90.
https://doi.org/10.1096/fj.07-8506com
Campos C, de Gregorio R, García-Nieto R, Gago F, Ortiz P, Alemany S. Regulation of cyclooxygenase activity by metamizole. Eur J Pharmaco 2008; 378(3):339-47.
https://doi.oeg/10.1016/s0014-2999(99)00477-x
Warner DT, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclooxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysis. Proc Natl Acad Sci USA 1999; 96(13):7563-8.
