FAİZE ELİF BAHADIR, Murat SANCAR, Gazi Giray TARHAN, Emre KOÇAK, Zeynep BUDANCAMANAK, Seda KARAASLAN, Elif DEMİRCİ RVANCIOĞLU DE, MERAL YÜKSEL, FERİHA ERCAN, YAŞAR İNCİ ALİCAN

Sıçanlarda yanık ile uyarılan uzak organ hasarı ve minosiklinin etkisi

Amaç: Bu çalışma, oral uygulanan minosiklinin -yarı sentetikikinci kuşak tetrasiklin– sıçanlarda yanık ile uyarılan karaciğer veböbrek hasarı üzerine anti-inflamatuvar potansiyelini incelemeyiamaçlamıştır.Gereç ve Yöntem: Çalışmada dişi Sprague-Dawley sıçanlar(250-300 g; n=7-8/grup) kullanıldı. Yanık ve taklit grupları, sırasıile 90 0C ve 25 0C’lik su banyosunda 10 saniye tutuldu. Minosiklin(20 mg/kg; günde iki kez; orogastrik yolla) yanık sonrası 24saat süreyle uygulandı. Dekapitasyon sonrası, biyokimyasalölçümler için gövde kanı toplandı. Histopatolojik incelemeve malondialdehit (MDA), glutatyon ve kemiluminisans (CL)ölçümleri için karaciğer ve böbrekler çıkarıldı.Bulgular: Minosiklin tedavisi yanık grubuna ait serum alaninaminotransferaz, aspartat aminotransferaz, kan üre azotu vekreatinin düzeylerine anlamlı bir etki göstermedi. Yanık grubundaartmış serum toplam oksidan durum (P<0.001) minosiklin ile geridöndürüldü (P<0.001) ve karaciğer mikroskopik hasar skoru hafifazalma (P<0.01) gösterdi. Minosiklin yanık grubunda artmış dokuMDA ve glutatyon düzeyleri üzerine anlamlı etki göstermedi ancakartmış luminol CL düzeylerini geri döndürdü (P<0.001, karaciğerve P<0.01, böbrek).Sonuç: Sıçanlara yanık sonrası 24 saat minosiklin tedavisikaraciğer ve böbrekte oksidan oluşumunu azaltmada etkinbulunmuştur; ancak bu dokuları oksidan hasara karşı hafif derecedekoruyucu bir etki göstermiştir.

Anahtar Kelimeler:

Böbrek, Karaciğer, Minosiklin, Sıçan, Yanık

Burn-induced distant organ injury in rats and the effect of minocycline

Objectives: This study aimed to examine the anti-inflammatorypotential of orally-administered minocycline, a semi-syntheticsecond-generation tetracycline, on burn-induced liver and kidneydamage in rats.Materials and Methods: Female Sprague-Dawley rats (250-300 g; n=7-8/group) were used. Burn and sham groups wereexposed to 90 0C and 25 0C water bath for 10 s, respectively.Minocycline (20 mg/kg; twice daily; orogastrically) wasadministered for 24 h post-burn. After decapitation, trunk bloodwas collected for biochemical assays. Liver and kidneys wereexcised for histopathological evaluation and malondialdehyde(MDA), glutathione and chemiluminescence (CL) assays.Results: Minocycline treatment did not exert a significant effecton serum alanine aminotransferase, aspartate aminotransferase,blood urea nitrogen, and creatinine levels of the burn group.Increased serum total oxidant status of the burn group was reversed(P<0.001) and liver microscopic lesion score showed a slightreduction (P<0.01) by minocycline. Minocycline did not cause asignificant effect on increased tissue MDA and glutathione levelsof the burn group but reversed the elevated luminol CL levels(P<0.001, for liver and P<0.01, for kidney, respectively).Conclusion: Minocycline treatment to rats for 24 h post-burnwas found to be effective to reduce oxidant production in the liverand kidney; however, it showed slight protection on these tissuesagainst oxidant damage.

Keywords:

Burn, Kidney, Liver, Minocycline, Rat,

PDF

___

Parihar A, Parihar MS, Milner S, Bhat S. Oxidative stress and anti-oxidative mobilization in burn injury. Burns 2008;34:6- 17. doi: 10.1016/j.burns.2007.04.009
Magnotti LJ, Xu DZ, Lu Q, Deitch EA. Gut-derived mesenteric lymph: a link between burn and lung injury. Arch Surg 1999;134:1333-41.
Moore FA. The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg 1999;178:449-53.
Sabeh F, Baxter CR, Norton SJ. Skin burn injury and oxidative stress in liver and lung tissues of rabbit models. Eur J Clin Chem Clin Biochem 1995;33:323-8.
Youn YK, Suh GJ, Jung SE, Oh SK, Demling R. Recombinant human growth hormone decreases lung and liver tissue lipid peroxidation and increases antioxidant activity after thermal injury in rats. J Burn Care Rehabil 1998;19:542-8.
Youn Y-K, LaLonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg 1992;25:249-65.
Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson’s disease. Curr Pharm Des 2004;10:679–86.
Koistinaho M, Malm TM, Kettunen MI, Goldsteins G, Starckx S, Kauppinen RA, et al. Minocycline protects against permanent cerebral ischemia in wild type but not in matrix metalloprotease-9-deficient mice. J Cereb Blood Flow Metab 2005;25:460–7. doi: 10.1038/sj.jcbfm.9600040
Lee SM, Yune TY, Kim SJ, Park DW, Lee YK, Kim YC, et al. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma 2003;20:1017–27. doi: 10.1089/089771503770195867
Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 2000;6:797–801. doi: 10.1038/77528
Padi SS, Kulkarni SK. Minocycline prevents the development of neuropathic pain, but not acute pain: possible antiinflammatory and antioxidant mechanisms. Eur J Pharmacol 2008;601:79-87. doi: 10.1016/j.ejphar.2008.10.018
Singh LP, Mishra A, Saha D, Swarnakar S. Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress. World J Gastroenterol 2011;17:3310-21. doi: 10.3748/wjg.v17.i28.3310
Pruzanski W, Greenwald RA, Street IO, La-leberte F, Stefanski E, Vadas P. Inhibition of enzymatic activity of phospholipase A2 by minocycline and doxycycline. Biochem Pharmacol 1992;44:1165–70.
Esterly NB, Koransky JS, Furey NL, Trevisan M. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol 1984;120:1308–13.
Gabler WL, Tsukuda N. The influence of divalent cations and doxycycline on iodoacetamide-inhibitable leukocyte adherence. Res Commun Chem Pathol Pharmacol 1991;74:131–40.
Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem 2005;94:819–27. doi.10.1111/j.1471-4159.2005.03219.x
Chang Y-W, Waxman SG. Minocycline attenuates mechanical allodynia and central sensitization following peripheral second-degree burn injury. J Pain 2010;11:1146- 54. doi. 10.1016/j.jpain.2010.02.010
Oktar BK, Yüksel M, Alican İ. The effect of alpha-melanocyte stimulating hormone on burn-induced oxidant production by rat peritoneal neutrophils. MMJ 2003;16:7-11.
Li Y, li T, Qi H, Yuan F. Minocycline protects against hepatic ischemia/reperfusion injury in a rat model. Biomed Rep 2015;3:19-24. doi: 10.3892/br.2014.381
Leite LM, Carvalho AG, Ferreira PL, Pessoa IX, Gonçalves DO, Lopes Ade A, et al. Anti-inflammatory properties of doxycycline and minocycline in experimental models: an in vivo and in vitro comparative study. Inflammopharmacol 2011;19:99-110. doi: 10.1007/s10787-011-0077-5
Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9.
Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11. doi: 10.1016/j.clinbiochem.2005.08.008
Aykaç G, Uysal M, Yalçın AS, Koçak-Toker N, Sivas A, Öz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione peroxidase and glutathione transferase in rat. Toxicology 1985:46:71–6.
Casini A, Ferrali M, Pompella AS, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am J Pathol 1986: 123: 520–31.
Haklar G, Ulukaya-Durakbaşa C, Yüksel M, Dağlı T, Yalçın AS. Oxygen radicals and nitric oxide in rat mesenteric ischemia-reperfusion: modulation by l-arginine and N-nitro- L-arginine methyl ester. Clin Exp Pharmacol Physiol 1998;25:908–12.
Rodriguez JL, Miller CG, Garner WL, Till GO, Guerrero P, Moore NP, et al. Correlation of the local and systemic cytokine response with clinical outcome following thermal injury. J Trauma 1993;34:684-94.
Hansbrough JF, Wikstrom T, Braide M, Tenenhaus M, Rennekampff OH, Kiessig V, et al. Neutrophil activation and tissue neutrophil sequestration in a rat model of thermal injury. J Surg Res 1996;61:17-22. doi: 10.1006/jsre.1996.0074
Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000;405:458-62.
Alexander JW, Boyce ST, Babcock GF, Gianotti L, Peck MD, Dunn DL, et al. The process of microbial translocation. Ann Surg 1990;212:496-510.
Dobke MK, Simoni J, Ninnemann TJ, Garrett J, Harnar TJ. Endotoxemia after burn injury: Effect of early excision on circulating endotoxin levels. J Burn Care Rehabil 1989;10:107-11.
Youn YK, Lalonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg 1995;16:30-6.
Nieman GF, Zerler BR. A role for the anti-inflammatory properties of tetracyclines in the prevention of acute lung injury. Curr Med Chem 2001;8:317-25.
Zhu S, Stavrosvskaya IG, Drozda M, Kim BY, Ona V, Li M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 2002;41:74-8. doi: 10.1038/417074a
Ryan ME, Greenwald RA, Golub LM. Potential of tetracyclines to modify cartilage breakdown in osteoarthritis. Curr Opin Rheumatol 1996;8:238–47.
Cazalis J, Tanabe S, Gagnon G, Sorsa T, Grenier D. Tetracyclines amd chemically modified tetracycline-3 (CMT-3) modultae cytokine secretion by lipopolysaccharidestimulated whole blood. Inflammation 2009;32:130-7. doi: 10.1007/s10753-009-9111-9
Parenti A, Indorato B, Paccosi S. Minocycline affects human neutrophil respiratory burst and transendothelial migration. Inflamm Res 2017;66:107-9. doi: 10.1007/s00011-016- 0999-x
Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem 2005;94: 819-27. doi: 10.1111/j.1471-4159.2005.03219.x
Pruzanski W, Greenwald RA, Street IO, La-leberte F, Stefanski E, Vadas P. Inhibition of enzymatic activity of phospholipase A2 by minocycline and doxycycline. Biochem Pharmacol 1992;44:1165-70.
Gabler WL, Tsukuda N. The influence of divalent cations and doxycycline on iodoacetamide-inhibitable leukocyte adherence. Res Commun Chem Pathol Pharmacol 1991;74: 131-40.
Thong YH, Ferrante A. Inhibition of mitogen-induced human lymphocyte proliferative responses by tetracycline analogues. Clin Exp Immunol 1979;35:443-6.
Davies GR, Simmond NJ, Stevens TRJ, Sheaf MT, Bnavala N, Laurensen IF, et al. Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut 1994;35:179-85.