Tavşan korneasında yüksek doz metilprednizolonun yanı sıra ozon (O3) tedavisinin hipoksi ile indüklenebilir faktör-1 alfa (HIF-la) ekspresyonu üzerine etkisi
Abstract
Giriş: Bir tavşan
modelinde sistemik olarak kullanılan yüksek doz metilprednizolon (MP)
uygulanmış kornea üzerinde ozon (O3) tedavisinin etkisini araştırmak.
Yöntem: Yirmi dört Yeni Zelanda Beyaz yetişkin erkek
tavşanı rastgele olarak sekiz hayvan içeren üç eşit gruba ayrıldı. Birinci grup
(n = 8) kontrol grubu olarak kullanıldı ve onlara hiçbir şey uygulanmadı, diğer
taraftan steroid grubu olarak adlandırılan diğer 2 grup, üç gün boyunca 20 mg /
kg / gün dozunda IM metilprednizolon enjeksiyonuna tabi tutuldu. Üç günlük MP
uygulamasından sonra, sadece üçüncü grup, 14 seans boyunca rektal insüflasyon
yoluyla 50 ug / mL O3 (20 mL O3) ile tedavi edildi. Üç grubun kornealarının
histopatolojik incelemesi yapıldı ve hipoksiye bağlı faktör-1 a (HIF-la)
ekspresyonu açısından değerlendirildi.
Bulgular: Sistemik olarak
uygulanan yüksek doz MP'nin steroid gruplarında kornea epitelinde erozyon ve
nekroza ve korneal stromada stromal parçalanmaya neden olduğu belirlendi (Grup
2 ve Grup 3). MP + O3 grubunda (Grup 3) histopatolojik bulgular hafifti.
HIF1-a'nın Grup 1 (kontrol grubu), Grup 2 (MP) ve Grup 3 (MP-O3) korneasında
ekspresyonu sırasıyla %17.9 ± 9.6, % 3.1 ± 1.0 ve % 6.4 ± 1.9 olarak ölçüldü.
Sonuç: MP ve MP-O3
tedavisi, her iki müdahale grubunda da tavşan korneasında HIF-la ekspresyonunu
azalttı. Bu iki grup arasında, HIF-la ekspresyonu MP-O3 grubunda sadece MP
grubuna göre nispeten yüksek kaldı.
References
- 1. Beck RW. The optic neuritis treatment trial. Implications for clinical practice. Optic Neuritis Study Group. Arch Ophthalmol 1992;110(3):331-2. https://doi.org/10.1001/archopht.1992.01080150029020
- 2. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3(10):721-32. https://doi.org/10.1038/nrc1187
- 3. Xia X, Kung AL. Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia. Genome Biol 2009;10(10):R113. https://doi.org/10.1186/gb-2009-10-10-r113
- 4. Eckle T, Köhler D, Lehmann R, El Kasmi K, Eltzschig HK. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation 2008;118(2):166-75. https://doi.org/10.1161/CIRCULATIONAHA.107.758516
- 5. Semenza GL. Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta 2011;1813(7):1263-8. https://doi.org/10.1016/j.bbamcr.2010.08.006
- 6. Ong SG, Lee WH, Theodorou L, Kodo K, Lim SY, Shukla DH, et al. HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore. Cardiovasc Res 2014;104(1):24-36. https://doi.org/10.1093/cvr/cvu172
- 7. Kucharz EJ. Hormonal control of collagen metabolism. Part II. Endocrinologie 1988;26(4):229-37. https://www.ncbi.nlm.nih.gov/pubmed/3062759
- 8. Ryu JS, Ko JH, Kim MK, Wee WR, Oh JY. Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway. Sci Rep 2017;7(1):4135. https://doi.org/10.1038/s41598-017-04509-8
- 9. Bourcier T, Forgez P, Borderie V, Scheer S, Rostène W, Laroche L. Regulation of human corneal epithelial cell proliferation and apoptosis by dexamethasone. Invest Ophthalmol Vis Sci 2000;41(13):4133–41. https://www.ncbi.nlm.nih.gov/pubmed/11095606
- 10. Bourcier T, Borderie V, Forgez P, Lombet A, Rostène W, Laroche L. In vitro effects of dexamethasone on human corneal keratocytes. Invest Ophthalmol Vis Sci 1999;40(6):1061-70. https://www.ncbi.nlm.nih.gov/pubmed/10235539
- 11. Yao L, Nie X, Shi S, Song S, Hao X, Li S, et al. Reciprocal regulation of HIF-1α and 15-LO/15-HETE promotes anti-apoptosis process in pulmonary artery smooth muscle cells during hypoxia. Prostaglandins Other Lipid Mediat 2012;99(3-4):96-106. https://doi.org/10.1016/j.prostaglandins.2012.09.001
- 12. Vidal S, Horvath E, Kovacs K, Kuroki T, Lloyd RV, Scheithauer BW. Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in pituitary tumours. Histol Histopathol. 2003;18(3):679-86. https://doi.org/10.14670/HH-18.679
- 13. Zhang C1, Qiang Q2, Jiang Y3, Hu L4, Ding X5, Lu Y6, Hu G7. Effects of hypoxia inducible factor-1α on apoptotic inhibition and glucocorticoid receptor downregulation by dexamethasone in AtT-20 cells. BMC Endocr Disord 2015;15:24. https://doi.org/10.1186/s12902-015-0017-2
The effect of ozone (O3) therapy in addition to high dose methylprednisolone on hypoxia inducible factor-1 alpha (HIF-1α) expression in rabbit cornea
Abstract
Introduction: To investigate the effect
of ozone (O3) therapy on cornea subjected to systemically used high dose
methylprednisolone (MP) in a rabbit model.
Methods: Twenty-four New Zealand White adult male
rabbits were randomly divided into three equal groups as containing eight
animals. The first group (n = 8) was used as the control group and nothing was
applied to them, whereas the other 2 groups named as steroid groups were
subjected to IM methylprednisolone injection at a dose of 20 mg/kg/day for
three days. After three days of MP administration, only the third group was
treated with 50-µg/mL O3 (20 mL O3) through the rectal insufflation for 14
sessions. The histopathological examination of corneas of three groups were
made, and they were also assessed regarding the expression of hypoxia-inducible
factor-1 α (HIF-1α).
Results: It was determined that systemically
administered high dose MP caused erosion and necrosis in corneal epithelium and
stromal disintegrations in corneal stroma in steroid groups (Group 2 and Group
3). In the MP + O3 group (Group 3), the histopathological findings were mild.
The expression of HIF1-α in the cornea of Group1 (control group), Group 2 (MP),
and Group 3 (MP-O3) was measured as, 17.9±9.6%, 3.1±1.0% and 6.4±1.9% respectively.
Conclusions: MP and MP-O3 therapy decreased HIF-1a expression in rabbit cornea in
both intervention groups. Between these two groups, HIF-1α expression remained
relatively high in the MP-O3 group than in the MP group alone.
References
- 1. Beck RW. The optic neuritis treatment trial. Implications for clinical practice. Optic Neuritis Study Group. Arch Ophthalmol 1992;110(3):331-2. https://doi.org/10.1001/archopht.1992.01080150029020
- 2. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3(10):721-32. https://doi.org/10.1038/nrc1187
- 3. Xia X, Kung AL. Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia. Genome Biol 2009;10(10):R113. https://doi.org/10.1186/gb-2009-10-10-r113
- 4. Eckle T, Köhler D, Lehmann R, El Kasmi K, Eltzschig HK. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation 2008;118(2):166-75. https://doi.org/10.1161/CIRCULATIONAHA.107.758516
- 5. Semenza GL. Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta 2011;1813(7):1263-8. https://doi.org/10.1016/j.bbamcr.2010.08.006
- 6. Ong SG, Lee WH, Theodorou L, Kodo K, Lim SY, Shukla DH, et al. HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore. Cardiovasc Res 2014;104(1):24-36. https://doi.org/10.1093/cvr/cvu172
- 7. Kucharz EJ. Hormonal control of collagen metabolism. Part II. Endocrinologie 1988;26(4):229-37. https://www.ncbi.nlm.nih.gov/pubmed/3062759
- 8. Ryu JS, Ko JH, Kim MK, Wee WR, Oh JY. Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway. Sci Rep 2017;7(1):4135. https://doi.org/10.1038/s41598-017-04509-8
- 9. Bourcier T, Forgez P, Borderie V, Scheer S, Rostène W, Laroche L. Regulation of human corneal epithelial cell proliferation and apoptosis by dexamethasone. Invest Ophthalmol Vis Sci 2000;41(13):4133–41. https://www.ncbi.nlm.nih.gov/pubmed/11095606
- 10. Bourcier T, Borderie V, Forgez P, Lombet A, Rostène W, Laroche L. In vitro effects of dexamethasone on human corneal keratocytes. Invest Ophthalmol Vis Sci 1999;40(6):1061-70. https://www.ncbi.nlm.nih.gov/pubmed/10235539
- 11. Yao L, Nie X, Shi S, Song S, Hao X, Li S, et al. Reciprocal regulation of HIF-1α and 15-LO/15-HETE promotes anti-apoptosis process in pulmonary artery smooth muscle cells during hypoxia. Prostaglandins Other Lipid Mediat 2012;99(3-4):96-106. https://doi.org/10.1016/j.prostaglandins.2012.09.001
- 12. Vidal S, Horvath E, Kovacs K, Kuroki T, Lloyd RV, Scheithauer BW. Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in pituitary tumours. Histol Histopathol. 2003;18(3):679-86. https://doi.org/10.14670/HH-18.679
- 13. Zhang C1, Qiang Q2, Jiang Y3, Hu L4, Ding X5, Lu Y6, Hu G7. Effects of hypoxia inducible factor-1α on apoptotic inhibition and glucocorticoid receptor downregulation by dexamethasone in AtT-20 cells. BMC Endocr Disord 2015;15:24. https://doi.org/10.1186/s12902-015-0017-2
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Original Research |
| Authors | |
| Publication Date | December 31, 2019 |
| Submission Date | December 11, 2019 |
| Acceptance Date | December 31, 2019 |
| Published in Issue | Year 2019Volume: 4 Issue: 3 |