The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

Open access


The influences of NSAIDs (Nonsteroidal Anti-inflammatory Drugs) – non-selective metamizole and selectively-acting tolfenamic acid were estimated on morphology, ultrastructure, and cytophysiological activity of canine (Ca) and equine (Eq) adipose-derived mesenchymal stem cells (ASCs). The lowest concentration of metamizole (0.01 mg/mL) stimulated the viability and cytophysiological activity of Ca ASCs and did not affect cell morphology. Stimulated cells possessed a proper, fibroblastic shape, with large, eccentrically located nuclei. Similar effects to those observed in Ca ASCs were found in Eq cells treated with both drugs. Cells cultivated with the intermediate (0.1 mg/mL) doses of NSAIDs displayed proper cell morphology, whereas cells cultivated in intermediate dose (0.1 mg/mL) became more flattened. The highest concentrations (1 mg/mL) of both drugs resulted in a cytotoxic effect in Ca and Eq ASCs. Based on these results, we conclude that stimulation of Ca and Eq ASCs with metamizole as well as Eq ASCs with tolfenamic acid can lead to positive effects only when the lowest drug concentrations are applied. This study indicates a different cellular response of canine and equine ASCs treated with metamizole and tolfenamic acid. The obtained data might be potentially useful in the study of functionalized veterinary biomaterials.

Biancone L, Bruno S, Deregibus MC, Tetta C, Camussi G (2012) Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant 27: 3037-3042.

Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, Gingerich DA, Harman R (2007) Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multi-center, controlled trial. Vet Ther 8: 272-284.

Caron JP, Genovese RL (2003) Principles and practices of joint disease treatment. In: Diagnostics and Management of Lameness in the Horse. 2nd ed., Missouri Elsevier Saunders 746-763.

Chang JK, Wang GJ, Tsai ST, Ho ML (2005) Nonsteroidal anti-inflammatory drug effects on osteoblastic cell cycle, cytotoxicity, and cell death. Connect Tissue Res 46: 200-210.

Chang JK, Li CJ, Wu SC, Yeh CH, Chen CH, Fu YC, Wang GJ, Ho ML (2007) Effects of anti-inflammatory drugs on proliferation, cytotoxicity and osteogenesis in bone marrow mesenchymal stem cells. Biochem Pharmacol 9: 1371-1382.

Chang JK, Wu SC, Wang GJ, Cho MH, Ho ML (2006) Effects of non-steroidal anti-inflammatory drugs on cell proliferation and death in cultured epiphyseal-articular chondrocytes of fetal rats. Toxicology 228: 111-123.

Chang JK, Li CJ, Liao HJ, Wang CK, Wang GJ, Ho ML (2009) Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. Toxicology 258:148-156.

Cipollone F, Prontera C, Pini B, Marini M, Fazia M, De Cesare D, Iezzi A, Ucchino S, Boccoli G, Saba V, Chiarelli F, Cuccurullo F, Mezzetti A (2001) Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation 104: 1921-927.

Crofford LJ (2013) Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 49: 15-9

Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M (2009) Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology 136: 978-989.

Grzesiak J, Marycz K, Czogala J, Wrzeszcz K, Nicpon J (2011) Comparison of behavior, morphology and morphometry of equine and canine adipose derived mesenchymal stem cells in culture. Int J Morph1 29: 012-1017.

Ho ML, Chang JK, Chuang LY, Hsu HK, Wang GJ (1999) Effects of nonsteroidal anti-inflammatory drugs and pros-taglandins on osteoblastic functions. Biochem Pharmacol 58: 983-990.

Holt DJ, Grainger DW (2011) Multinucleated giant cells from fibroblast cultures. Biomaterials 32: 3977-3987.

Kalinski K, Marycz K, Czogala J, Serwa E, Janeczek W (2012) An application of scanning electron microscopy combined with roentgen microanalysis (SEM-EDS) in canine urolithiasis. J Electron Microsc (Tokyo) 61: 47-55

Kania M, Mikolajewska D, Marycz K, Kobielarz M (2009) Effect of diet of mechanical properities of horse's hair. Acta Bioeng 11: 53-57

Krzak-Ros J, Marycz K, Donesz-Sikorska A, Smieszek A, Grzesiak J (2013) Evaluation of the cellular response to hybrid materials (SiO2/TiO2), depending on the used precursors in the sol-gel method. Przem Chem 92: 1101

Lou E, Fujisawa S, Barlas A, Romin Y, Manova-Todorova K, Moore MA, Subramanian S (2012) Tunneling Nanotubes: A new paradigm for studying intercellular communication and therapeutics in cancer. Comun Integr Biol 5: 399-403

Marycz K, Grzesiak J, Wrzeszcz K, Golonka P (2012a) Adipose stem cell combined with plasma-based implant bone tissue differentiation in vitro and in horse with a phalanx digitalis distalis fracture: case report. Vet Med 57: 610-617

Marycz K, Krzak-Ros J, Smieszek A, Grzesiak J, Donesz-Sikorska A (2013) Effect of oxide materials synthesized with sol-gel method on adhesion of mesenchymal stem cells. Przem Chem 92: 1000

Marycz K, Toker NY, Grzesiak J, Wrzeszcz K, Golonka P (2012b) The Therapeutic Effect of Autogenic Adipose Derived Stem Cells Combined with Autogenic Platelet Rich Plasma in Tendons Disorders in Horses in vitro and in vivo research. J Anim Vet Ad 11: 4324-4331.

Marycz K, Toker NY, Smieszek A, Nicpon J (2014) The morphology and proliferation rate of canine and equine adipose derived mesenchymal stem cells cultured with flunixin meglumine-in vitro. Kafkas Univ Vet Fak 20: 201-207

Marycz K, Smieszek A, Grzesiak J, Donesz-Sikorska A, Krzak-Ros J (2013) Application of bone marrow and adipose-derived mesenchymal stem cells for testing the biocompatibility of metal-based biomaterials functionalized with ascorbic acid. Biomed Mater 8

Marycz K, Krzak-Ros J, Donesz-Sikorska A, Smieszek A (2014) The morphology, proliferation rate, and population doubling time factor of adipose-derived mesenchymal stem cells cultured on to non-aqueous SiO2, TiO2, and hybrid sol-gel-derived oxide coatings. Biomed Mater Res 102: 4017-4026

Müller M, Raabe O, Addicks K, Wenisch S, Arnhold S (2011) Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells. Cell Biol Int 35: 235-248

Qi Y, Feng G, Yan W (2012) Mesenchymal stem cell-based treatment for cartilage defects in osteoarthritis. Mol Biol Rep 39: 5683-5689.

Ratajczak MZ (2011) The emerging role of microvesicles in cellular therapies for organ/tissue regeneration. Nephrol Dial Transplant 26: 1453-1456.

Svendsen CN (2013) Back to the future: how human induced pluripotent stem cells will transform regenerative medicine. Hum Mol Genet22: R32-R38.

Urban MK (2000) COX-2 specific inhibitors offer improved advantages over traditional NSAIDs. Orthopedics 23: 761-774.

Wang Y, Chen X, Zhu W, Zhang H, Hu S, Cong X (2006) Growth inhibition of mesenchymal stem cells by aspirin: involvement of the WNT/beta-catenin signal pathway. Clin Exp Pharmacol Physiol 33: 696-701

Witek-Krowiak A, Podstawczyk D, Chojnacka K, Dawiec A, Marycz K (2013) Modelling and optimization of chromium III biosorption on soybean meal. Cent Eur J Chem 11: 1505-1517.

Polish Journal of Veterinary Sciences

The Journal of Committee of Veterinary Sciences of Polish Academy of Sciences and University of Warmia and Mazury in Olsztyn

Journal Information

IMPACT FACTOR 2016: 0.697
5-year IMPACT FACTOR: 0.773

CiteScore 2016: 0.73

SCImago Journal Rank (SJR) 2016: 0.315
Source Normalized Impact per Paper (SNIP) 2016: 0.486


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 204 122 7
PDF Downloads 153 113 8