Sıçanlarda yanık ile uyarılan uzak organ hasarı ve minosiklinin etkisi

Abstract

Amaç: Bu çalışma, oral uygulanan minosiklinin -yarı sentetik

ikinci kuşak tetrasiklin– sıçanlarda yanık ile uyarılan karaciğer ve

böbrek hasarı üzerine anti-inflamatuvar potansiyelini incelemeyi

amaçlamıştır.

Gereç ve Yöntem: Çalışmada dişi Sprague-Dawley sıçanlar

(250-300 g; n=7-8/grup) kullanıldı. Yanık ve taklit grupları, sırası

ile 90 0C ve 25 0C’lik su banyosunda 10 saniye tutuldu. Minosiklin

(20 mg/kg; günde iki kez; orogastrik yolla) yanık sonrası 24

saat süreyle uygulandı. Dekapitasyon sonrası, biyokimyasal

ölçümler için gövde kanı toplandı. Histopatolojik inceleme

ve malondialdehit (MDA), glutatyon ve kemiluminisans (CL)

ölçümleri için karaciğer ve böbrekler çıkarıldı.

Bulgular: Minosiklin tedavisi yanık grubuna ait serum alanin

aminotransferaz, aspartat aminotransferaz, kan üre azotu ve

kreatinin düzeylerine anlamlı bir etki göstermedi. Yanık grubunda

artmış serum toplam oksidan durum (P<0.001) minosiklin ile geri

döndürüldü (P<0.001) ve karaciğer mikroskopik hasar skoru hafif

azalma (P<0.01) gösterdi. Minosiklin yanık grubunda artmış doku

MDA ve glutatyon düzeyleri üzerine anlamlı etki göstermedi ancak

artmış luminol CL düzeylerini geri döndürdü (P<0.001, karaciğer

ve P<0.01, böbrek).

Sonuç: Sıçanlara yanık sonrası 24 saat minosiklin tedavisi

karaciğer ve böbrekte oksidan oluşumunu azaltmada etkin

bulunmuştur; ancak bu dokuları oksidan hasara karşı hafif derecede

koruyucu bir etki göstermiştir.

Keywords

• Böbrek,Karaciğer,Minosiklin,Sıçan,Yanık

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

Abstract

Objectives: This study aimed to examine the anti-inflammatory

potential of orally-administered minocycline, a semi-synthetic

second-generation tetracycline, on burn-induced liver and kidney

damage in rats.

Materials and Methods: Female Sprague-Dawley rats (250-

300 g; n=7-8/group) were used. Burn and sham groups were

exposed to 90 0C and 25 0C water bath for 10 s, respectively.

Minocycline (20 mg/kg; twice daily; orogastrically) was

administered for 24 h post-burn. After decapitation, trunk blood

was collected for biochemical assays. Liver and kidneys were

excised for histopathological evaluation and malondialdehyde

(MDA), glutathione and chemiluminescence (CL) assays.

Results: Minocycline treatment did not exert a significant effect

on 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 slight

reduction (P<0.01) by minocycline. Minocycline did not cause a

significant effect on increased tissue MDA and glutathione levels

of 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-burn

was found to be effective to reduce oxidant production in the liver

and kidney; however, it showed slight protection on these tissues

against oxidant damage.

Keywords

• Burn,Kidney,Liver,Minocycline,Rat

References

1. 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
2. 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.
3. Moore FA. The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg 1999;178:449-53.
4. 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.
5. 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.
6. Youn Y-K, LaLonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg 1992;25:249-65.
7. Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson’s disease. Curr Pharm Des 2004;10:679–86.
8. 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

9. 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
10. 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
11. 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
12. 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
13. 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.
14. Esterly NB, Koransky JS, Furey NL, Trevisan M. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol 1984;120:1308–13.
15. 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.
16. 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
17. 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
18. 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.
19. 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
20. 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
21. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9.
22. 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
23. 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.
24. 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.
25. 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.
26. 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.
27. 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
28. 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.
29. 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.
30. 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.
31. Youn YK, Lalonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg 1995;16:30-6.
32. 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.
33. 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
34. Ryan ME, Greenwald RA, Golub LM. Potential of tetracyclines to modify cartilage breakdown in osteoarthritis. Curr Opin Rheumatol 1996;8:238–47.
35. 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
36. 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
37. 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
38. 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.
39. 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.
40. Thong YH, Ferrante A. Inhibition of mitogen-induced human lymphocyte proliferative responses by tetracycline analogues. Clin Exp Immunol 1979;35:443-6.
41. 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.