Numan KARAARSLAN, Duygu YASAR SİRİN, Aykut DEMİRKİRAN, Derya BAYKIZ, İbrahim YİLMAZ, Ozkan ATES

Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?

Aim: Nimodipine is used to prevent cerebrovascular-originated ischemic neurological deficits, yet its effects on nucleus pulposus (NP) cells or annulus fibrosus (AF) cells weren’t studied. This study aimed to examine nimodipine’s effects on vitality and proliferation of chondroadherin (CHAD), type II collagen (COL2A1), and hypoxia-inducible factor 1 alpha (HIF 1α) gene expression in human primary NP/AF cells.Material and Methods: NP/AF cell cultures obtained from 6 patients who underwent microdiscectomy were treated with 100 µMolar nimodipine and analyzed at 0, 24, and 48 h. Data were evaluated using one-way ANOVA and post-hoc Tukey HSD with 95% confidence interval.Results: We observed suppressed cell proliferation and increased necrosis in nimodipine-treated NP/AF cell cultures, especially degenerated tissue. COL2A1 gene expression wasn’t detected in any experimental groups. CHAD and HIF 1α expression had timedependent decreases in control. CHAD and HIF 1α expression were found to decrease at 24h, but increased at 48h in degenerated tissue. In nimodipine-applied intact tissues, CHAD expression was stable at 24h but 1.62 times higher than control at 48h. HIF 1α levels were lower than control.Conclusion: In nimodipine-treated degenerated AF/NP cultures, CHAD and HIF 1α expressions had time-dependent decreases. However, after complete RT-PCR data evaluation, no correlation between nimodipine application and gene expression occurred.

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Product information of nimodipine. http://www.bayerresources. com.au/resources/uploads/pi/file9406.pdf Accessed date 31.03.2018
Monzani D, Genovese E, Pini LA, Di Berardino F, Alicandri Ciufelli M, Galeazzi GM, et al. Nimodipine in otolaryngology: from past evidence to clinical perspectives. Acta Otorhinolaryngol Ital 2015;35(3):135-45.
Wang F, Yin YH, Jia F, Jiang JY. Antagonism of R-type calcium channels significantly improves cerebral blood flow after subarachnoid hemorrhage in rats. J Neurotrauma 2010;27(9):1723-32.
Shen H, Liang P, Qiu S, Zhang B, Wang Y, Lv P. The role of Na(+), K(+)-ATPase in the hypoxic vasoconstriction in isolated rat basilar artery. Vascul Pharmacol 2016;81:53-60.
Zhou YT, Yu LS, Zeng S, Huang YW, Xu HM, Zhou Q. Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management. Ther Clin Risk Manag 2014;10:17-26.
Lasner TM, Weil RJ, Riina HA, King JT Jr, Zager EL, Raps EC, et al. Cigarette smoking-induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg 1997;87(3):381-4.
Cohn A, Ehlke S. Association of Current and Lifetime DSM-IV Drug use Disorder Diagnoses to 6-Month Changes in Smoking Behavior in Risky Drinking Smokers: A Pilot Study. Subst Use Misuse 2017;52(13):1784-94.
Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromently B. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol 2011;54(4):773-94.
Goodwin WH. The use of forensic DNA analysis in humanitarian forensic action: The development of a set of international standards. Forensic Sci Int 2017;278:221-7.
Inrig JK, Molina C, D’Silva K, Kim C, Van Buren P, Allen JD, et al. Effect of low versus high dialysate sodium concentration on blood pressure and endothelial-derived vasoregulators during hemodialysis: a randomized crossover study. Am J Kidney Dis 2015;65(3):464-73.
Gumustas SA, Yilmaz I, Isyar M, Sirin DY, Batmaz AG, Gonultas A, et al. Is it possible to expedite ressearches for effects of pharmacological agents on primary cell culture which is obtained from high grade fibular osteosarcoma? J Clin Exp Oncol 2016;5(6):1-8.
Guzelant AY, Isyar M, Yilmaz I, Sirin DY, Cakmak S, Mahirogullari M. Are chondrocytes damaged when rheumatologic inflammation is suppressed? Drug Chem Toxicol 2017;40(1):13-23.
Karaarslan N, Yilmaz I, Isyar M, Ozbek H, Akyuva Y, Sirin DY, et al. Do Nitric Oxide Synthases Enzyme Inhibitors Affect Chondrocyte Activity? Merit Res J Med Med Sci 2017;5(12):635-45.
Oznam K, Sirin DY, Yilmaz I, Kaya YE, Isyar M, Gumustas SA, et al. Iopromide-and gadopentetic acid-derived preparates used in MR arthrography may be harmful to chondrocytes. J Orthop Surg Res 2017;2(1):98.
Sirin DY, Karaarslan N. Evaluation of the effects of pregabalin on chondrocyte proliferation and CHAD, HIF-1α, and COL2A1 gene expression. Arch Med Sci 2018.
Finsterer J, Scorza FA. Effects of antiepileptic drugs on mitochondrial functions, morphology, kinetics, biogenesis, and survival. Epilepsy Res 2017;136:5-11.
Kruse AC, Weiss DR, Rossi M, Hu J, Hu K, Eitel K, et al. Muscarinic receptors as model targets and antitargets for structure$based ligand discovery. Mol Pharmacol 2013;84(4):528-40.
Karaarslan N, Yilmaz I, Ozbek H, Sirin Yasar D, Kaplan N, Akyuva Y, et al. Are specific gene expressions of extracellular matrix and nucleus pulposus affected by primary cell cultures prepared from intact or degenerative intervertebral disc tissues? Turk Neurosurg 2018;22.
Hanley EN Jr DR, McCulloch JA. Surgical Indication and Techniques International Society for the Study of the Lumbar Spine: The Lumbar SpineThe Lumbar Spine 2nd edition. Philadelphia PA: WB Saunders. 1996; p. 492-524.
Feng G, Jin X, Hu J, Ma H, Gupte MJ, Liu H, et al. Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype. Biomaterials 2011;32(32):8182-9.
Zhou X, Tao Y, Liang C, Zhang Y, Li H, Chen Q. BMP3 alone and together with TGF-β promote the differentiation of human mesenchymal stem cells into a nucleus pulposus-like phenotype. Int J Mol Sci 2015;16(9):20344-59.
Rosenzweig DH, Tremblay Gravel J, Bisson D, Ouellet JA, Weber MH, Haglund L. Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications. Eur Cell Mater 2017;33:240-51.
Ehlicke F, Freimark D, Heil B, Dorresteijn A, Czermak P. Intervertebral disc regeneration: influence of growth factors on differentiation of human mesenchymal stem cells (hMSC). Int J Artif Organs 2010;33(4):244-52.
Subramani K, Ghrew M. Severe myocardial depression following intravenous nimodipine for aneurysmal subarachnoid haemorrhage. Intensive Care Med 2004;30(7):1498-9.
Porchet F, Chiolero R, de Tribolet N. Hypotensive effect of nimodipine during treatment for aneurysmal subarachnoid haemorrhage, Acta Neurochir (Wien) 1995;137(1-2): 62-9.
Livonia MI. Nimodipine capsule package insert. Major Pharmaceutical. (2015). http://medlibrary.org/lib/rx/meds/ nimodipine-1/page/4/2018/01/01. accessed date 18.03.2018
Albanna W, Weiss M, Conzen C, Clusmann H, Schneider T, Reinsch M, et al. Systemic and Cerebral Concentration of Nimodipine During Established and Experimental Vasospasm Treatment. World Neurosurg 2017;102:459-65.
Ben Fredj N, Grange J, Sadoul R, Richard S, Goldberg Y, Boyer V. Depolarization-induced translocation of the RNA-binding protein Sam68 to the dendrites of hippocampal neurons. J Cell Sci 2004;117(Pt 7):1079-90.
Wang GH, Liu Y, Wu XB, Lu Y, Liu J, Qin YR, et al. Neuroprotective effects of human umbilical cord-derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis. Cytotherapy 2016;18(1):53-64.
Stein G, Srivastava MK, Merker HJ, Neubert D. Effects of calcium channel blockers on the development of early rat post implantation embryos in culture. Arch Toxicol 1990;64(8):623- 38.
Behroozi-Lak T, Zarei L, Moloody-Tapeh M, Farhad N, Mohammadi R. Protective effects of intraperitoneal administration of nimodipine on ischemia-reperfusion injury in ovaries: Histological and biochemical assessments in a rat model. J Pediatr Surg 2017;52(4):602-8.
St-Onge M, Dubé PA, Gosselin S, Guimont C, Godwin J, Archambault PM, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol (Phila) 2014;52(9):926-44.
Navarro-Gonzalez MF, Grayson TH, Meaney KR, Cribbs LL, Hill CE. Non-L-type voltage-dependent calcium channels control vascular tone of the rat basilar artery. Clin Exp Pharmacol Physiol 2009;36(1):55-66.
Gumustas SA, Yilmaz I, Isyar M, Sirin DY, Batmaz AG, Ugras AA, et al. Assessing the negative impact of phenyl alkanoic acid derivative, a frequently prescribed drug for the suppression of pain and inflammation, on the differentiation and proliferation of chondrocytes. J Orthop Surg Res 2016;11(1):70.
Kraus P, Lufkin T. Bovine annulus fibrosus cell lines isolated from intervertebral discs. Genom Data 2016;10:83-4.
van den Akker GG, Surtel DA, Cremers A, Rodrigues-Pinto R, Richardson SM,Hoyland JA, et al. Novel immortal human cell lines reveal subpopulations in the nucleus pulposus. Arthritis Res Ther 2014;16(3):R135.
Oh CD, Im HJ, Suh J, Chee A, An H, Chen D. Rho-Associated Kinase Inhibitor Immortalizes Rat Nucleus Pulposus and Annulus Fibrosus Cells: Establishment of Intervertebral Disc Cell Lines With Novel Approaches. Spine (Phila Pa 1976) 2016;41(5):255-61.
Gumustas F, Yilmaz I, Sirin DY, Gumustas SA, Batmaz AG, Isyar M, et al. Chondrocyte proliferation, viability and differentiation is declined following administration of methylphenidate utilized for the treatment of attention$deficit/hyperactivity disorder. Hum Exp Toxicol 2017;36(9):981-92.
Yan Z, Yin L, Wang Z, Ye J, Zhang Z, Li R, et al. A novel organ culture model of mouse intervertebral disc tissues. Cells Tissues Organs 2016;201(1):38-50.
Moreira CD, Carvalho SM, Mansur HS, Pereira MM. Thermogelling chitosan-collagen-bioactive glass nanoparticle hybrids as potential injectable systems for tissue engineering. Mater Sci Eng C Mater Biol Appl 2016; 58:1207-16.
Zhu JJ, Xu YQ, He JH, Yu HP, Huang CJ, Gao JM, et al. Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish. J Appl Toxicol 2014;34(2):139-48.