Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue

Akgun,Feride  Sinem; Sirin,Duygu  Yasar; Yilmaz,Ibrahim; Karaarslan,Numan; Ozbek,Hanefi; Simsek,Abdullah  Talha; Kaya,Yasin  Emre; Kaplan,Necati; Akyuva,Yener; Caliskan,Tezcan; Ates,Ozkan

doi:10.3892/etm.2019.7576

Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue

Authors:
- Feride Sinem Akgun
- Duygu Yasar Sirin
- Ibrahim Yilmaz
- Numan Karaarslan
- Hanefi Ozbek
- Abdullah Talha Simsek
- Yasin Emre Kaya
- Necati Kaplan
- Yener Akyuva
- Tezcan Caliskan
- Ozkan Ates
View Affiliations

Affiliations: Department of Emergency Medicine, School of Medicine, Istanbul Maltepe University, Istanbul 34843, Turkey, Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Namik Kemal University, Tekirdag 59100, Turkey , Department of Medical Pharmacology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey, Department of Neurosurgery, School of Medicine, Namik Kemal University, Tekirdag 59100, Turkey, Department of Orthopedics and Traumatology, School of Medicine, Abant Izzet Baysal University, Bolu 14000, Turkey, Department of Neurosurgery, Corlu Reyap Hospital, Istanbul Rumeli University, Tekirdag 59680, Turkey, Department of Neurosurgery, Gaziosmanpasa Taksim Training and Research Hospital, Istanbul 34433, Turkey, Department of Neurosurgery, Istanbul Koc University Hospital, Istanbul Koc University, Istanbul 34010, Turkey
Published online on: May 13, 2019 https://doi.org/10.3892/etm.2019.7576
Pages: 216-224
Copyright: © Akgun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to evaluate the effects of dipyrone, an indispensable analgesic, anti‑pyretic and anti‑spasmodic used in emergency departments, on nucleus pulposus and annulus fibrosus cells in vitro. After surgical biopsy, primary cell cultures were prepared from intact intervertebral disc tissues. Dipyrone was administered to the cultures in the experimental groups except for the control group. The data obtained were statistically evaluated. The proliferation was identified to be suppressed via MTT analysis. The gene expression profile of the intervertebral disc cells in the dipyrone‑treated groups was significantly changed. The expression of chondroadherin, cartilage oligo matrix protein, interleukin‑1β and metalloproteinase (MMP)‑19 genes were decreased, but MMP‑13 and MMP‑7 genes expressions were increased, as determined via reverse transcription‑quantitative PCR. AO/PI staining revealed that no apoptotic or other type of cell death was detectable after administration of dipyrone does not mean that the drug is innocuous. The occurrence of cellular senescence and/or the halt of cell proliferation may also be important mechanisms underlying the adverse inhibitory effects of dipyrone. Therefore, prior to administering dipyrone in clinical practice, all possible adverse effects of this drug should be considered.

View Figures

View References

1	Yilmaz I and Ulugol A: The effect of nitric oxide synthase inhibitors on the development of analgesic tolerance to dipyrone in mice. Int J Neurosci. 119:755–764. 2009. View Article : Google Scholar : PubMed/NCBI
2	Garcia S, Canoniero M, Lopes G and Soriano AO: Metamizole use among Hispanics in Miami: Report of a survey conducted in a primary care setting. South Med J. 99:924–926. 2006. View Article : Google Scholar : PubMed/NCBI
3	Dilmen OK, Akcil EF, Tunali Y, Karabulut ES, Bahar M, Altindas F, Vehid H and Yentur E: Postoperative analgesia for supratentorial craniotomy. Clin Neurol Neurosurg. 146:90–95. 2016. View Article : Google Scholar : PubMed/NCBI
4	Claros OR, Silva CH, Consolmagno H, Sakai AT, Freddy R and Fugita OE: Current practices in the management of patients with ureteral calculi in the emergency room of a university hospital. Clinics (Sao Paulo). 67:415–418. 2012. View Article : Google Scholar : PubMed/NCBI
5	Florentino IF, daSilva DP, Martins JL, da Silva TS, Santos FC, Tonussi CR, Vasconcelos GA, Vaz BG, Lião LM, Menegatti R and Costa EA: Pharmacological and toxicological evaluations of the new pyrazole compound (LQFM-021) as potential analgesic and anti-inflammatory agents. Inflammopharmacology. 24:265–275. 2016. View Article : Google Scholar : PubMed/NCBI
6	Sirin DY and Karaarslan N: Evaluation of the effects of pregabalin on chondrocyte proliferation and CHAD, HIF-1α, and COL2A1 gene expression. Arch Med Sci. 14:1340–1347. 2018. View Article : Google Scholar : PubMed/NCBI
7	Karaarslan N, Yilmaz I, Sirin DY, Ozbek H, Kaplan N, Kaya YE, Akyuva Y, Gurbuz MS, Oznam K and Ates O: Does pregabalin used in the treatment of neuropathic pain damage intervertebral disc tissue? Exp Ther Med. 16:1259–1265. 2018.PubMed/NCBI
8	Pompeia C, Boaventura MF and Curi R: Antiapoptotic effect of dipyroneon HL-60, Jurkat and Raji cell lines submitted to UV irradiation, arachidonic acid and cycloheximide treatments. Int Immunopharmacol. 1:2173–2182. 2001. View Article : Google Scholar : PubMed/NCBI
9	Akyuva Y, Karaarslan N, Yilmaz I, Ozbek H, Sirin DY, Gurbuz MS, Kaya YE, Kaplan N and Ates O: How scaffolds, which are polymeric drug delivery systems allowing controlled release, can be tested in human primary nucleus pulposus and annulus fibrosus cell cultures? Merit Res J Med Med Sci. 5:477–487. 2017.
10	Silav G, Ergün H, Dolgun H, Sancak T, Sargon MF and Egemen N: Dipyrone attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. J Neurosurg Sci. 61:380–387. 2017.PubMed/NCBI
11	Zhang Y, Wang X, Baranov SV, Zhu S, Huang Z, Fellows-Mayle W, Jiang J, Day AL, Kristal BS and Friedlander RM: Dipyrone inhibits neuronal cell death and diminishes hypoxic/ischemic brain injury. Neurosurgery. 69:942–956. 2011. View Article : Google Scholar : PubMed/NCBI
12	Grossman R, Ram Z, Perel A, Yusim Y, Zaslansky R and Berkenstadt H: Control of postoperative pain after awake craniotomy with local intradermal analgesia and metamizol. Isr Med Assoc J. 9:380–382. 2007.PubMed/NCBI
13	Donaubauer HH, Kief H, Kramer M, Krief K, Mayer D and Schütz E: Investigations on the carcinogenicity of dipyrone in rats. Toxicol App Pharmacol. 81:443–451. 1985. View Article : Google Scholar
14	Kramer M: Chronic toxicity of pyrazolones: The problem of nitrosation. Br J Clin Pharmacol. 10 (Suppl 2):S313–S317. 1980. View Article : Google Scholar
15	Maj S and Lis Y: The incidence of metamizole sodium-induced agranulocytosis Poland. J Int Med Res. 30:488–495. 2002. View Article : Google Scholar : PubMed/NCBI
16	Giorgi M, Aupanun S, Lee HK, Poapolathep A, Rychshanova R, Vullo C, Faillace V and Laus F: Pharmacokinetic profiles of the active metamizole metabolites in healthy horses. J Vet Pharmacol Ther. 40:165–171. 2017. View Article : Google Scholar : PubMed/NCBI
17	Schütter AF, Tünsmeyer J and Kästner SB: Influence of metamizole on 1) minimal alveolar concentration of sevoflurane in dogs and 2) on thermal and mechanical nociception in conscious dogs. Vet Anaesth Analg. 43:215–226. 2016. View Article : Google Scholar : PubMed/NCBI
18	Yaşar Şirin D, Yılmaz İ, İsyar M, Öznam K and Mahiroğulları M: Does leukocyte-poor or leukocyte-rich platelet-rich plasma applied with biopolymers have superiority to conventional platelet-rich plasma applications on chondrocyte proliferation? Eklem Hastalik Cerrahisi. 28:142–151. 2017. View Article : Google Scholar : PubMed/NCBI
19	Bundscherer AC, Malsy M, Gruber MA, Graf BM and Sinner B: Acetaminophen and metamizole induce apoptosis in HT 29 and SW 480 colon carcinoma cell lines in vitro. Anticancer Res. 38:745–751. 2018.PubMed/NCBI
20	Malsy M, Graf B and Bundscherer A: Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1. BMC Pharmacol Toxicol. 18:772017. View Article : Google Scholar : PubMed/NCBI
21	Guzelant AY, Isyar M, Yilmaz İ, Sirin DY, Cakmak S and Mahirogullari M: Are chondrocytes damaged when rheumatologic inflammation is suppressed? Drug Chem Toxicol. 40:13–23. 2017. View Article : Google Scholar : PubMed/NCBI
22	Arkhipchuk VV, Goncharuk VV, Chernykh VP, Maloshtan LN and Gritsenko IS: Use of a complex approach for assessment of metamizole sodium and acetylsalicylic acid toxicity, genotoxicity and cytotoxicity. J Appl Toxicol. 24:401–407. 2004. View Article : Google Scholar : PubMed/NCBI
23	Rutges J, Creemers LB, Dhert W, Milz S, Sakai D, Mochida J, Alini M and Grad S: Variations in gene and protein expression in human nucleus pulposus in comparison with annulus fibrosus and cartilage cells: potential associations with aging and degeneration. Osteoarthritis Cartilage. 18:416–423. 2010. View Article : Google Scholar : PubMed/NCBI
24	van den Akker GG, Surtel DA, Cremers A, Richardson SM, Hoyland JA, van Rhijn LW, Voncken JW and Welting TJ: Novel immortal cell lines support cellular heterogeneity in the human annulus fibrosus. PLoS One. 11:01444972016. View Article : Google Scholar
25	Zhang YG, Guo X, Sun Z, Jia G, Xu P and Wang S: Gene expression profiles of disc tissues and peripheral blood mononuclear cells from patients with degenerative discs. J Bone Miner Metab. 28:209–219. 2010. View Article : Google Scholar : PubMed/NCBI
26	Goode AP, Marshall SW, Kraus VB, Renner JB, Stürmer T, Carey TS, Irwin DE and Jordan JM: Association between serum and urine biomarkers and lumbar spine individual radiographic features: The johnston county osteoarthritis project. Osteoarthritis Cartilage. 20:1286–1293. 2012. View Article : Google Scholar : PubMed/NCBI
27	Yilmaz I, Gokay NS, Bircan R, Saracoglu GV, Dervisoglu S and Gokce A: How different methodologies of harvesting and analysing the samples affect the test results in determining joint mediators. Arthritis. 2013:6319592013. View Article : Google Scholar : PubMed/NCBI
28	Gokay NS, Yilmaz I, Komur B, Demiroz AS, Gokce A, Dervisoglu S and Gokay BV: A Comparison of the effects of neuronal nitric oxide synthase and inducible nitric oxide synthase inhibition on cartilage damage. Biomed Res Int. 2016:78573452016. View Article : Google Scholar : PubMed/NCBI
29	Goupille P, Jayson MI, Valat JP and Freemont AJ: Matrix metalloproteinases: The clue to intervertebral disc degeneration? Spine (Phila Pa 1976). 23:1612–1626. 1998. View Article : Google Scholar : PubMed/NCBI
30	Yurube T, Takada T, Suzuki T, Kakutani K, Maeno K, Doita M, Kurosaka M and Nishida K: Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration. Arthritis Res Ther. 14:R512012. View Article : Google Scholar : PubMed/NCBI
31	Weiler C, Nerlich AG, Zipperer J, Bachmeier BE and Boos N: 2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J. 11:308–320. 2002. View Article : Google Scholar : PubMed/NCBI
32	Roberts S, Caterson B, Menage J, Evans EH, Jaffray DC and Eisenstein SM: Matrix metalloproteinases and aggrecanase: Their role in disorders of the human intervertebral disc. Spine (Phila Pa 1976). 25:3005–3013. 2000. View Article : Google Scholar : PubMed/NCBI
33	Sedlacek R, Mauch S, Kolb B, Schätzlein C, Eibel H, Peter HH, Schmitt J and Krawinkel U: Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis. Immunobiology. 198:408–423. 1998. View Article : Google Scholar : PubMed/NCBI
34	NCBI, . Matrix metallopeptidase 19 [Homo sapiens (human)]. https://www.ncbi.nlm.nih.gov/gene/4327March 3–2018
35	Gruber HE, Ingram JA and Hanley EN Jr: Immunolocalization of MMP-19 in the human intervertebral disc: Implications for disc aging and degeneration. Biotech Histochem. 80:157–162. 2005. View Article : Google Scholar : PubMed/NCBI
36	Nishida Y, D'Souza AL, Thonar EJ and Knudson W: Stimulation of hyaluronan metabolism by interleukin-1alpha in human articular cartilage. Arthritis Rheum. 43:1315–1326. 2000. View Article : Google Scholar : PubMed/NCBI
37	Hu B, Xu C, Tian Y, Shi C, Zhang Y, Deng L, Zhou H, Cao P, Chen H and Yuan W: Inflammatory microRNA-194 and −515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration. Oncotarget. 8:49303–49317. 2017.PubMed/NCBI
38	Lv FJ, Peng Y, Lim FL, Sun Y, Lv M, Zhou L, Wang H, Zheng Z, Cheung KMC and Leung VYL: Matrix metalloproteinase 12 is an indicator of intervertebral disc degeneration co-expressed with fibrotic markers. Osteoarthritis Cartilage. 24:1826–1836. 2016. View Article : Google Scholar : PubMed/NCBI