Effect of doxycycline and meloxicam on cytokines, brain-derived neurotrophic factor, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and cyclooxygenase-2 in brain | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 12، دوره 23، شماره 10، دی 2020، صفحه 1328-1334 اصل مقاله (532.59 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2020.45193.10527 | ||
| نویسندگان | ||
| Ayşe ER* 1؛ Devran Coskun2؛ emre Bahcivan3؛ Burak DIK1 | ||
| 1Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey | ||
| 2Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Siirt University, Siirt, Turkey | ||
| 3Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey | ||
| چکیده | ||
| Objective(s): Prevention of inflammation in early stages will be useful in maintaining vitality of the organism. The objective of this study was to evaluate the effects of doxycycline (DOX) or meloxicam (MLX) monotherapy and combination therapy on the levels of inflammatory mediators in the brain tissues of rats with Escherichia coli lipopolysaccharide (LPS)-induced brain inflammation. Materials and Methods: Seventy-eight rats were divided into the following groups: control (n=6), LPS (0.5 µg/10 µl intracranial) (n=18), LPS (0.5 µg/10 µl intracranial)+DOX (40 mg/kg intraperitoneal) (n=18), LPS (0.5 µg/10 µl intracranial)+MLX (2 mg/kg intraperitoneal) (n=18) and LPS (0.5 µg/10 µl intracranial)+DOX (40 mg/kg intraperitoneal)+MLX (2 mg/kg intraperitoneal) (n=18) groups. Brain tissues were harvested from all rats in the control group and from six rats each in the four experimental groups at 1, 3 and 6 hr under anaesthesia. The levels of tumor necrosis factor α (TNFα), interleukin 4 (IL-4), IL-6, IL-10, IL-17, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 3 (TIMP-3) and cyclooxygenase 2 (COX-2) in the brain tissues were measured using ELISA kits with ELISA device. Results: LPS administration increased proinflammatory cytokines (TNF, IL-6, IL-17), and MMP-3 levels and decreased anti-inflammatory cytokines (IL-10, IL-4), and BDNF levels. The lowest TNFα levels were detected in the LPS+MLX group (P<0.05). All the drug treatment groups showed decreased IL-17 and COX-2 levels compared to the LPS groups. Conclusion: DOX or MLX monotherapy exerts neuroprotective effects against brain inflammation by decreasing proinflammatory cytokine levels and by increasing anti-inflammatory cytokines levels. | ||
| کلیدواژهها | ||
| Brain؛ Doxycycline؛ Inflammation؛ Meloxicam؛ Neuroprotective | ||
| مراجع | ||
|
1. Catorce MN, Gevorkian G. LPS-induced murine neuroinflammation model: main features and suitability for pre-clinical assessment of nutraceuticals. Curr Neuropharmacol 2016; 14: 155-164. 2. Yazar E, Bulbul A, Avci GE, Er A, Uney K, Elmas M, et al. Effects of enrofloxacin, flunixin meglumine and dexamethasone on disseminated intravascular coagulation, cytokine levels and adenosine deaminase activity in endotoxaemia in rats. Acta Vet Hung 2010; 58: 357-367. 3. Zheng X, Liang Y, Kang A, Ma SJ, Xing L, Zhou YY, et al. Peripheral immunomodulation with ginsenoside Rg1 ameliorates neuroinflammation-induced behavioral deficits in rats. Neuroscience 2014; 256: 210-222. 4. Lee EJ, Ko HM, Jeong YH, Park EM, Kim HS. β-Lapachone suppresses neuroinflammation by modulating the expression of cytokines and matrix metalloproteinases in activated microglia. J Neuroinflammation 2015; 12: 133. 5. Waisman A, Hauptmann J, Regen T. The role of IL-17 in CNS diseases. Acta Neuropathol 2015; 129: 625-637. 6. Minciullo PL, Catalano A, Mandraffino G, Casciaro M, Crucitti A, Maltese G, et al. Inflammaging and anti-inflammaging: The role of cytokines in extreme longevity. Arch Immunol Ther Exp (Warsz) 2016; 64: 111-126. 7. Romero LI, Schettini G, Lechan RM, Dinarello CA, Reichlin S. Bacterial lipopolysaccharide induction of IL-6 in rat telencephalic cells is mediated in part by IL-1. Neuroendocrinology 1993; 57: 892-897. 8. Lehmann AK, Halstensen A, Sørnes S, Røkke O, Waage A. High levels of interleukin 10 in serum are associated with fatality in meningococcal disease. Infect Immun 1995; 63: 2109-2112. 9. Granert C, Raud J, Waage A, Lindquist L. Effects of polysaccharide fucoidin on cerebrospinal fluid interleukin-1and tumor necrosis factor alpha in pneumococcal meningitis in the rabbit. Infect Immun 1999; 67: 2071-2074. 10. Offner H, Subramanian S, Parker SM, Afentoulis ME, Vandenbark AA, Hurn PD. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab 2006; 26: 654-665. 11. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. Cyclooxygenase in biology and disease. FASEB J. 1998; 12: 1063-1073. 12. Laube M, Kniess T, Pietzsch J. Development of anti-oxidant COX-2 ınhibitors as radioprotective agents for radiation therapy-A hypothesis-driven review. Antioxidants (Basel) 2016 ;5:14. 13. Kalmar B, Kittel A, Lemmens R, Környei Z, Madarasz E. Cultured astrocytes react to LPS with increased cyclooxygenase activityand phagocytosis. Neurochem Int 2001; 38: 453-461. 14. Hempstead BL. Brain-derived neurotrophic factor: Three ligands, many actions. Trans Am Clin Climatol Assoc 2015; 126: 9-19. 15. Hachisu M, Konishi K, Hosoi M, Tani M, Tomioka H, Inamoto A, et al. Beyond the hypothesis of serum anticholinergic activity in Alzheimer’s disease: Acetylcholine neuronal activity modulates brain-derived neurotrophic factor production and inflammation in the brain. Neurodegener Dis 2015; 15: 182-187. 16. Yang Y, Rosenberg GA. Matrix metalloproteinases as therapeutic targets for stroke. Brain Res. 2015; 1623: 30-38. 17. Yazar E. Chemotherapeutics, In: Yazar E, editor. Veterinary Drug, Istanbul, Nobeltip, 2018. p. 85-224. 18. Bastos LF, de Oliveira AC, Watkins LR, Moraes MF, Coelho MM. Tetracyclines and pain. Naunyn Schmiedebergs Arch Pharmacol 2012; 385: 225-241. 19. Bostanci N, Akgül B, Tsakanika V, Allaker RP, Hughes FJ, McKay IJ. Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with aggregatibacter Actinomycete mcomitans. Cytokine 2011; 56: 656-661. 20. Tras B, Elmas M. Analgesic, antipyretic and anti-inflammatory drugs. In: Yazar E, editör. Veterinary Drug, Istanbul, Nobeltip, 2018. p. 311-334. 21. Desmarais G, Charest G, Fortin D, Bujold R, Mathieu D, Paquette B. Cyclooxygenase-2 inhibitor prevents radiation-enhanced infiltration of F98 glioma cells in brain of Fischer rat. Int J Radiat Biol 2015; 91: 624-633. 22. Yu L, Jiang R, Su Q, Yu H, Yang J. Hippocampal neuronal metal ion imbalance related oxidative stress in a rat model of chronic aluminum exposure and neuroprotection of meloxicam. Behav Brain Funct 2014; 10: 6. 23. Yi C, Zhang Z, Wang W, Zug C, Schluesener HJ, Zhang Z. Doxycycline attenuates peripheral inflammation in rat experimental autoimmune neuritis. Neurochem Res 2011; 36: 1984-1990. 24. Spiess BM, Pot SA, Florin M, Hafezi F. Corneal collagen cross-linking (CXL) for the treatment of melting keratitis in cats and dogs: A pilot study. Vet Ophthalmol. 2014;17:1-11. 25. Takahashi M, Kawaguchi M, Shimada K, Nakashima T, Furuya H. Systemic meloxicam reduces tactile allodynia development after L5 single spinal nerve injury in rats. Reg Anesth Pain Med 2005; 30 :351-355. 26. De Groot CJ, Langeveld CH, Jongenelen CA, Montagne L, Van Der Valk P, Dijkstra CD. Establishment of human adult astrocyte cultures derived from postmortem multiple sclerosis and control brain and spinal cord regions: Immunophenotypical and functional characterization. J Neurosci Res. 1997; 49: 342-354. 27. Ward JL, Harting MT, Cox CS Jr, Mercer DW. Effects of ketamine on endotoxin and traumatic brain injury induced cytokine production in the rat. J Trauma. 2011;70:1471-1479. 28. Espinosa-Oliva AM, de Pablos RM, Herrera AJ. Intracranial injection of LPS in rat as animal model of neuroinflammation. Methods Mol Biol 2013; 1041: 295-305. 29. Capone ML, Tacconelli S, Di Francesco L, Sacchetti A, Sciulli MG, Patrignani P. Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat 2007; 82: 85-94. 30. Liu WC, Ding WL, Gu HY, Chen MF, Hu JJ. Lipopolysaccharide-induced cerebral inflammatory damage and the therapeutic effect of platelet activating factor receptor antagonist. Neurosci Bull 2007; 23: 271-276. 31. Chen G, McCuskey RS, Reichlin S. Blood interleukin-6 and tumor necrosis factor alpha elevation after intracerebroventricular injection of Escherichia coli endotoxin in the rat is determined by two opposing factors: Peripheral induction by LPS transferred from brain to blood and inhibition of peripheral response by a brain-mediated mechanism. Neuroimmunomodulation 2000; 8: 59-69. 32. Mpiga P, Mansour S, Morisset R, Beaulieu R, Ravaoarinoro M. Sustained interleukin-6 and interleukin-8 expression following infectionwith Chlamydia trachomatis serovar L2 in a HeLa/THP-1 cell co-culturemodel. Scand J Immunol 2006; 63: 199-207. 33. de Miranda AS, Lacerda-Queiroz N, de Carvalho Vilela M, Rodrigues DH, Rachid MA, Quevedo J, et al. Anxiety-like behavior and proinflammatory cytokine levels in the brain of C57BL/6 mice infected with Plasmodium berghei (strain ANKA). Neurosci Lett 2011; 491: 202-206. 34. Zhang Z, Yang WZ, Zhu ZZ, Hu QQ, Chen YF, He H, et al. Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced mouse dry eye model. Invest Ophthalmol Vis Sci 2014; 55: 2963-2974. 35. Hassan MH, Ghobara MM. Antifibrotic effect of meloxicam in rat liver: Role of nuclear factor kappa B, proinflammatory cytokines, and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol 2016; 389: 971-983. 36. Barichello T, Generoso JS, Milioli G, Elias SG, Teixeira AL. Pathophysiology of bacterial infection of the central nervous system and its putative role in the pathogenesis of behavioral changes. Braz J Psychiatr 2013; 35: 81-87. 37. Brian JE, Jr Moore SA, Faraci FM. Expression and vascular effects of cyclooxygenase-2 in brain. Stroke 1998; 29: 2600-2606. 38. Cao C, Matsumura K, Ozaki M, Watanabe Y. Lipopolysaccharide injected into the cerebral ventricle evokes fever through induction of cyclooxygenase-2 in brain endothelial cells. J Neurosci 1999; 19: 716-725. 39. Teismann P, Ferger B. Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson’s disease. Synapse 2001; 39: 167-174. 40. Han L, Ren Q. Protective effect of meloxicam against acute radiation-induced brain injury in rats. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014; 30: 375-378. 41. Crawford YG, Gauthier ML, Joubel A, Mantei K, Kozakiewicz K, Afshari CA, et al. Histologically normal human mammary epithelia with silenced p16 (INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell 2004; 5: 263-273. 42. Luo C, Zhang H. The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer. Mediators Inflamm 2017; 2015:5126048. 43. Eimerbrink MJ, White JD, Pendry RJ, Hodges SL, Sadler LN, Wiles JD, et al. Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin. Behav Brain Res 2015; 288: 50-53. 44. Mello BS, Monte AS, McIntyre RS, Soczynska JK, Custodio CS, Cordeiro RC, et al. Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration. J Psychiatr Res 2013; 47: 1521-1529. 45. Lai AY, Todd KG. Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines. Glia 2006; 53 :809-816. 46. Bruschi F, Pinto B. The significance of matrix metalloproteinases in parasitic infections involving the central nervous system. Pathogens 2013; 2: 105-129. 47. Mandal, M, Mandal, A, Das, S, Chakraborti T, Sajal C. Clinical implications of matrix metalloproteinases. Mol Cell Biochem 2003;252: 305-29. , 48. Giraudon P, Buart S, Bernard A, Belin MF. Cytokines secreted by glial cells infected with HTLV-I modulate the expression of matrix metalloproteinases (MMPs) and their natural inhibitör (TIMPs): possible involvement in neurodegenerative processes. Mol Psychiatry 1997; 2: 107-110. 49. Zou X, Wu Z, Huang J, Liu P, Qin X, Chen L, et al. The role of matrix metalloproteinase-3 in the doxycycline attenuation of intracranial venous hypertension-induced angiogene. Neurosurgery 2018; 83: 1317-1327. 50. Cho Y, Son HJ, Kim EM, Choi JH, Kim ST, Ji IJ, et al. Doxycycline is neuroprotective against nigral dopaminergic degeneration by a dual mechanism involving MMP-3. Neurotox Res 2009; 16: 361-371. 51. Lazzarini M, Martin S, Mitkovski M, Vozari RR, Stühmer W, Bel ED. Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model. Glia 2013; 61: 1084-1100. | ||
|
آمار تعداد مشاهده مقاله: 940 تعداد دریافت فایل اصل مقاله: 558 |
||