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Asitretin-Metotreksat Uygulanmış Ratların İnce Bağırsak Dokusunda Polifenol Oksidaz Aktivitesi Üzerine Alfa-Lipoik Asitin Etkileri

Yıl 2022, Cilt: 1 Sayı: 3, 28 - 37, 30.12.2022

Öz

Amaç: Asitretin, lipofilik zayıf bir asit olan suda az çözünen ve yağ dokusunda az biriken A vitamini analoğudur. Aynı zamanda anti-inflamatuar ve anti-proliferatif etkili non-immünosupresifdir. Timidilat sentetaz ve dihidrofolat redüktaz inhibitörü olan metotreksat ise bir folik asit analoğudur. Günümüzde de kanser tedavilerinin yanında mikozis fungoides, pitriyazis rubra pilaris, dermatomiyozit, sarkoidoz, egzama gibi hastalıkların tedavisinde de kullanılan Metotreksat aynı zamanda bir anti-folat antimetabolit ajandır. Ayrıca Asitretin ile kombinasyon halinde tedavide de kullanılmaya başlanmıştır. Bu çalışmada, Asitretin-Metotreksat uygulaması sonucunda meydana gelebilecek serbest radikallerin neden olduğu hasarın giderilmesinde güçlü bir antioksidan olan Alfa Lipoik Asit ratlara verilmiştir. Böylece oluşabilecek oksidatif hasarı onarma da önemli rol oynayan Alfa Lipoik Asitin ince barsak dokusundaki polifenol oksidaz (1.10.3.1) enzim aktivitesi üzerine etkisinin araştırılması amaçlanmıştır. Aktif bölgelesinde bakır içeren Polifenol oksidaz, fenolik bileşiklerin moleküler oksijen ile oksidasyonunu katalizleyen oksidoredüktaz sınıfı bir enzimdir.

Yöntem: Kontrol grubu, Alfa Lipoik Asit grubu, Asitretin+Metotreksat grubu ve Asitretin+Metotreksat+Alfa Lipoik Asit grubu olarak dört çalışma grubu oluşturulmuştur. Ratlara enjeksiyon işlemleri her sabah aynı saatte yapılmıştır ve enjeksiyondan 24 saat önce de aç bırakılmışlardır. Asitretin, Metotreksat ve Alfa Lipoik Asit % 0.9’luk NaCl’de çözülmüştür ve intraperitonal enjeksiyonla ratlara verilmiştir. Ratlar, enjeksiyondan sonraki 7. günde servikal dislokasyon ile sakrifiye edilmiştir. Bunu takiben kalp perfüzyonu işlemi yapılmış ve ince bağırsakları çıkarılmıştır. Örnekler önce homojenize edildi sonra sonikasyon ve santrifüj işlemleri uygulandı. Santrifüj işleminden sonra, elde edilen ince bağırsak homojenatları Polifenol oksidaz aktivite tayini için kullanılmıştır.

Bulgular ve Sonuç: Alfa Lipoik Asit, Asitretin + Metotreksat ve Asitretin + Metotreksat + Alfa Lipoik Asit grupları kontrol grubu ile karşılaştırılmıştır. Bunun sonucunda Alfa Lipoik Asit grubunun Kontrol grubu ile hemen hemen aynı aktiviteye sahip olduğu (%1,65 aktivasyon) gözlenirken Asitretin + Metotreksat grubu %10, Asitretin + Metotreksat + Alfa Lipoik Asit grubunun ise %25 aktivasyon gösterdiği gözlenmiştir. Asitretin + Metotreksat grubu ile Asitretin + Metotreksat + Alfa Lipoik Asit grubu karşılaştırıldığında Asitretin + Metotreksat + Alfa Lipoik Asit grubunun %13,5 daha fazla aktivasyon gösterdiği de belirlenmiştir. Alfa Lipoik Asit, tek başına verildiğinde ince bağırsak dokusunda Polifenol oksidaz aktivitesinde anlamlı bir fark göstermezken, Asitretin + Metotreksat kombinasyonu ile verildiğinde Polifenol oksidaz aktivitesini artırmıştır.

Destekleyen Kurum

ONDOKUZ MAYIS ÜNİVERSİTESİ

Proje Numarası

PYO.FEN.1904.18.014

Kaynakça

  • An, J., Zhang, D., Wu, J., Li, J., Teng X, Gao X, Xia Y. (2017). The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis. Pharmacol Res. 121, 58-168.
  • Arpag, H., Gül, M., Aydemir, Y., Atilla, N., Yiğitcan, B., Cakir, T., Polat, C., Þehirli, Ö., Sayan, M. (2018). Protective effects of alpha lipoic acid on methotrexate-ınduced oxidative lung injury in rats. J. Invest. Surg. 31(2), 107-113.
  • Athoumani Ali, S., Dıraman, E., Solmaz, F., G. (2020). The investigation of the effect of alpha lipoic acid on lung polyphenol oxidase activity in acitretin and methotrexate given rats. Bull Biotechnol.,1(1), 19-22.
  • Bedoui, Y., Guillot, X., Sélambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M. C., Ralandison S., Gasque, P. (2019). Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci. 20(20).
  • Bhuiyan, Z. H., Chowdhury, M.K. (2016). Acitretin in dermatology a review. Bangladesh
  • Biewenga, G. P., Haenen, G. R., & Bast, A. (1997). The pharmacology of the antioxidant lipoic acid. Gen Pharmacol, 29(3), 315-331.
  • Braun, J., Rau R. (2009). An update on methotrexate. Curr Opin Rheumatol. 21(3), 216-23.
  • Chan, E.S., Cronstein, B. N. (2010). Methotrexate--how does it really work? Nat. Rev. Rheumatol. 6(3), 175-8.
  • Chande, N., Wang, Y., MacDonald, J. K., McDonald, J.W. (2014). Methotrexate for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. Aug 27;(8):CD006618.
  • Data, P. (1995). Alpha-lipoic acid. Arzneimittelforschung, 45, 872-874.
  • Davis, S.A., Yentzer, B.A., Feldman, S. R., (2013). Acitretin prescribing patterns in women of childbearing potential. J. Drugs Dermatol, 12(7):799-802.
  • Golbidi, S., Badran, M., Laher, I. (2011). Diabetes and alpha lipoic Acid. Front Pharmacol. 2, 69.
  • Hannoodee, M., Mittal, M. (2022). Methotrexate. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan. PMID: 32310574 Bookshelf ID: NBK556114.
  • Holthoewer, D., Endres, K., Schuck, F., Hiemke, C., Schmitt, U., & Fahrenholz, F. (2012). Acitretin, an enhancer of alpha-secretase expression, crosses the blood-brain barrier and is not eliminated by P-glycoprotein. Neurodegenerative Diseases, 10(1-4), 224-228.
  • Hung, S. Y., Boucias, D.G. (1996). Phenoloxidase activity in the hemolymph of naive and Beauvaria bassiana infected Spodoptera exigua larvae. J. Invert. Pathol. 67, 35-40.
  • Ighani, A., Partridge, A.C.R., Shear, N.H., Lynde, C., Gulliver, W.P., Sibbald, C., Fleming, P. (2019). Comparison of management guidelines for moderate-to-severe plaque psoriasis: A review of phototherapy, systemic therapies, and biologic agents. J. Cutan. Med. Surg., 23(2), 204-221.
  • Kahler, W., Kuklinski, B., Ruhlmann, C., Plotz, C. (1993). Diabetes mellitus-a free radical associated disease. Results of adjuvant antioxidant supplementation, Z. Gesamte Inn. Med., 48, 223- 232.
  • Khamaisi, M., Potashnik, R., Tirosh, A., Demshchak, E., Rudich, A., Tritschler, H., Bashan, N. (1997). Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin diabetic rats. Metabolism, 46(7), 763-768.
  • Kilinc, G., Dursun, A., Tuncer, K., Esin, H., Emiroglu, M. (2021). Inflammatory Colitis due to methotrexate toxicity in a patient with psoriasis: a case report, Med Records, 3(1),41-43.
  • Lagarce, L., Zenut, M., Lainé-Cessac, P. (2015). Methotrexate pharmacology. J. Gynecol. Obstet. Biol.Reprod. (Paris), 44(3),203-211.
  • Lotfi, M., Moniruzzaman, M., Mutalib, M. A., Wilfred, C. D., Alitheen, N. B., & Goto, M. (2016). Analysis of multiple solvation interactions of methotrexate and ammonium based ionic liquids using COSMO-RS. Procedia Engineering, 148, 459-466. Med. J 45(2), 98-100.
  • Guenther, L.C., Kunynetz, R., Lynde, C.W., Sibbald, R.G., Toole, J., Vender, R., Zip, C. (2017). Acitretin use in dermatology. J. Cutan. Med. Surg., 21(3), 2-12.
  • Maritim, A.C., Sanders, R.A., Watkins III J.B. (2003). Effects of α-lipoic acid on biomarkers of oxidative stres in streptozotocin-induced diabetic rats. J Nutr Biochem 14(5), 288-294.
  • Mehrtens, S.H., de la Hera, I., Shankar, S. (2018). Case of keratoacanthoma centrifugum marginatum treated with acitretin. BMJ Case Rep. Nov 01.
  • Molz, P., & Schröder, N. (2017). Potential therapeutic effects of lipoic acid on memory deficits related to aging and neurodegeneration. Frontiers in pharmacology, 8, 849.
  • Nomura, M., Sumiya, R., Ono, H. et al. (2021).Cessation of methotrexate and a small intestinal resection provide a good clinical course for a patient with a jejunum perforation induced by amethotrexate-associated lymphoproliferative disorder: a case report. World J Surg Onc 19, 4. https://doi.org/10.1186/s12957-020-02114-0
  • Ortiz, N. E. G., Nijhawan, R.I., Weinberg, J. M. (2013). Acitretin. Dermatol Ther, 26(5), 390-9.
  • Packer, L., Cadenas, E. (2011). Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr. 48(1), 26-32.
  • Reed L. J. (1998). From lipoic acid to multi-enzyme complexes. Protein Sci. 7, 220–224. 10.1002/pro.5560070125.
  • Rudrapal, M., Shubham, J., Kha, K. J., Dukhyil, A. B., Ansari, M.A., Alomar, M. N., Fahad M., Alshabrmi, F. M., Palai S., Prashanta Kumar Deb, P.K., Devi ajlakshmi Devi. (2022). Dietary polyphenols and their role in oxidative stress-ınduced human diseases: Insights Into protective effects, antioxidant potentials and mechanism(s) of action. Front Pharmacol. 14(13), 806470.
  • Shay, K. P., Moreau, R. F., Smith, E. J., Smith, A. R., Hagen, T. M. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim. Biophys. Acta 1790, 1149 1160. doi: 10.1016/j.bbagen.2009.07.026
  • Sadowska, M., Garbutt, J., Lesiak, A. (2022). Pros and cons of using systemic acitretin in the paediatric population. Postepy Dermatol Alergol. 39(1):34-38.
  • Schmidt, A.M., Hori, O., Brett, J., Yan, S.D., Wautier, J.L., Stern, D. (1994). Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler. Thromb. 14, 1521–1528.
  • Sezgin, F.G., Dıraman, E. & İncilay Torunoğlu, E. (2022). Rat Beyin Dokusunda Asitretin –Metotreksat Kombinasyonunun ve Α-Lipolik Asit’in Polifenol Oksidaz Aktivitesi Üzerine Etkileri. European Journal of Science and Technology, (37), 165-169.
  • Shiga, S., Machida, T., Yanada, T., Machida, M., Hirafuji, M., Iizuka, K. (2020). The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats. Journal of Pharmacological Sciences. 143, 1, 30-38.
  • Skillen, L.A, Corry, A. (2019). Combination therapy of sirolimus and acitretin in solid organ transplant recipients: a new cutaneous adverse event. Clin Exp Dermatol. 44(1):62-63.
  • Steffens, J.C, Harel, E, Hunt, M.D. (1994) Polyphenol oxidase. In BE Ellis, ed, Genetic Engineering of Plant Secondary Metabolism. Plenum Press, New York, pp 275–312.
  • Vallianou, N., Evangelopoulos, A., Koutalas, P. (2009). Alpha-lipoic Acid and diabetic neuropathy.Rev Diabet Stud. Winter 6(4), 230-6.
  • Wang, Y.H., Tsai, D. (2014). Small intestine perforation in a 58-year-old man with Darier disease after 25 months of oral acitretin therapy. Dermatologica Sinica. 32, 39-42.
  • Weinblatt, M.E, Coblyn, J.S., Fox, D.A., Fraser, P.A., Holdsworth, D.E., Glass, D.N., TrenthamD.E. (1985). Efficacy of low-dose methotrexate in rheumatoid arthritis. N. Engl. J. Med.28;312(13):818-822.
  • Zito, P.M, Mazzoni, T. (2022). Acitretin. In: StatPearls [Internet]. Treasure Island (FL): Stat Pearls Publishing; Sep 25.

Effects of Alpha-Lipoic Acid On Polyphenol Oxidase Activity in Small Intestine Tissue of Rats Treated With Acitretin - Methotrexate Combination

Yıl 2022, Cilt: 1 Sayı: 3, 28 - 37, 30.12.2022

Öz

Background and Aim: Acitretin is a vitamin A analogue, which is a lipophilic weak acid, less soluble in water and less accumulated in adipose tissue. It is also non-immunosuppressive with anti-inflammatory and anti-proliferative effects. Methotrexate, an inhibitor of thymidylate synthetase and dihydrofolate reductase, is a folic acid analogue. Today, Methotrexate, which is used in the treatment of diseases such as mycosis fungoides, pityriasis rubra pilaris, dermatomyositis, sarcoidosis, eczema, as well as cancer treatments, is also an anti-folate antimetabolite agent. It has also been used together with Acitretin in treatment. In this study, Alpha Lipoic Acid, which is a powerful antioxidant, was given to rats to eliminate the damage caused by free radicals that may occur as a result of Acitretin-Methotrexate application. Thus, it is aimed to investigate the effect of Alpha Lipoic Acid, which plays an important role in repairing the oxidative damage that may occur, on the polyphenol oxidase (1.10.3.1) enzyme activity in the small intestine tissue. Polyphenol oxidase, containing copper in its active site, is an oxidoreductase class enzyme that catalyzes the oxidation of phenolic compounds with molecular oxygen.

Materials and Methods: Four study groups were formed as Control Group, Alpha Lipoic Acid Group, Acitretin+Methotrexate Group and Acitretin+Methotrexate+Alpha Lipoic Acid Group. The injection procedures applied to the rats were performed at the same time every morning and they were fasted 24 hours before the injection. Acitretin, Methotrexate and Alpha lipoic acid were dissolved in 0.9% NaCl and given to rats by intraperitoneal injection. Rats were sacrificed by cervical dislocation on the 7th day after injection. Following this, cardiac perfusion was performed and the small intestines were removed. The samples were first homogenized, then sonication and centrifugation processes were applied. After centrifugation, the obtained small intestine homogenates were used for Polyphenol oxidase activity determination.

Result and Conclusion: Alpha Lipoic Acid, Acitretin + Methotrexate and Acitretin + Methotrexate + Alpha Lipoic Acid groups were compared with the control group. As a result, while it was observed that the Alpha Lipoic Acid group had almost the same activity with the Control group (1.65% activation), the Acitretin + Methotrexate group showed 10% activation, the Acitretin + Methotrexate + Alpha Lipoic Acid group showed 25% activation. When the Acitretin + Methotrexate group was compared with the Acitretin + Methotrexate + Alpha Lipoic Acid group, it was also determined that the Acitretin + Methotrexate + Alpha Lipoic Acid group showed 13.5% more activation. While Alpha Lipoic Acid did not show a significant difference in Polyphenol oxidase activity in small intestine tissue when given alone, it increased Polyphenol oxidase activity when given with Acitretin + Methotrexate combination.

Proje Numarası

PYO.FEN.1904.18.014

Kaynakça

  • An, J., Zhang, D., Wu, J., Li, J., Teng X, Gao X, Xia Y. (2017). The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis. Pharmacol Res. 121, 58-168.
  • Arpag, H., Gül, M., Aydemir, Y., Atilla, N., Yiğitcan, B., Cakir, T., Polat, C., Þehirli, Ö., Sayan, M. (2018). Protective effects of alpha lipoic acid on methotrexate-ınduced oxidative lung injury in rats. J. Invest. Surg. 31(2), 107-113.
  • Athoumani Ali, S., Dıraman, E., Solmaz, F., G. (2020). The investigation of the effect of alpha lipoic acid on lung polyphenol oxidase activity in acitretin and methotrexate given rats. Bull Biotechnol.,1(1), 19-22.
  • Bedoui, Y., Guillot, X., Sélambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M. C., Ralandison S., Gasque, P. (2019). Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci. 20(20).
  • Bhuiyan, Z. H., Chowdhury, M.K. (2016). Acitretin in dermatology a review. Bangladesh
  • Biewenga, G. P., Haenen, G. R., & Bast, A. (1997). The pharmacology of the antioxidant lipoic acid. Gen Pharmacol, 29(3), 315-331.
  • Braun, J., Rau R. (2009). An update on methotrexate. Curr Opin Rheumatol. 21(3), 216-23.
  • Chan, E.S., Cronstein, B. N. (2010). Methotrexate--how does it really work? Nat. Rev. Rheumatol. 6(3), 175-8.
  • Chande, N., Wang, Y., MacDonald, J. K., McDonald, J.W. (2014). Methotrexate for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. Aug 27;(8):CD006618.
  • Data, P. (1995). Alpha-lipoic acid. Arzneimittelforschung, 45, 872-874.
  • Davis, S.A., Yentzer, B.A., Feldman, S. R., (2013). Acitretin prescribing patterns in women of childbearing potential. J. Drugs Dermatol, 12(7):799-802.
  • Golbidi, S., Badran, M., Laher, I. (2011). Diabetes and alpha lipoic Acid. Front Pharmacol. 2, 69.
  • Hannoodee, M., Mittal, M. (2022). Methotrexate. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan. PMID: 32310574 Bookshelf ID: NBK556114.
  • Holthoewer, D., Endres, K., Schuck, F., Hiemke, C., Schmitt, U., & Fahrenholz, F. (2012). Acitretin, an enhancer of alpha-secretase expression, crosses the blood-brain barrier and is not eliminated by P-glycoprotein. Neurodegenerative Diseases, 10(1-4), 224-228.
  • Hung, S. Y., Boucias, D.G. (1996). Phenoloxidase activity in the hemolymph of naive and Beauvaria bassiana infected Spodoptera exigua larvae. J. Invert. Pathol. 67, 35-40.
  • Ighani, A., Partridge, A.C.R., Shear, N.H., Lynde, C., Gulliver, W.P., Sibbald, C., Fleming, P. (2019). Comparison of management guidelines for moderate-to-severe plaque psoriasis: A review of phototherapy, systemic therapies, and biologic agents. J. Cutan. Med. Surg., 23(2), 204-221.
  • Kahler, W., Kuklinski, B., Ruhlmann, C., Plotz, C. (1993). Diabetes mellitus-a free radical associated disease. Results of adjuvant antioxidant supplementation, Z. Gesamte Inn. Med., 48, 223- 232.
  • Khamaisi, M., Potashnik, R., Tirosh, A., Demshchak, E., Rudich, A., Tritschler, H., Bashan, N. (1997). Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin diabetic rats. Metabolism, 46(7), 763-768.
  • Kilinc, G., Dursun, A., Tuncer, K., Esin, H., Emiroglu, M. (2021). Inflammatory Colitis due to methotrexate toxicity in a patient with psoriasis: a case report, Med Records, 3(1),41-43.
  • Lagarce, L., Zenut, M., Lainé-Cessac, P. (2015). Methotrexate pharmacology. J. Gynecol. Obstet. Biol.Reprod. (Paris), 44(3),203-211.
  • Lotfi, M., Moniruzzaman, M., Mutalib, M. A., Wilfred, C. D., Alitheen, N. B., & Goto, M. (2016). Analysis of multiple solvation interactions of methotrexate and ammonium based ionic liquids using COSMO-RS. Procedia Engineering, 148, 459-466. Med. J 45(2), 98-100.
  • Guenther, L.C., Kunynetz, R., Lynde, C.W., Sibbald, R.G., Toole, J., Vender, R., Zip, C. (2017). Acitretin use in dermatology. J. Cutan. Med. Surg., 21(3), 2-12.
  • Maritim, A.C., Sanders, R.A., Watkins III J.B. (2003). Effects of α-lipoic acid on biomarkers of oxidative stres in streptozotocin-induced diabetic rats. J Nutr Biochem 14(5), 288-294.
  • Mehrtens, S.H., de la Hera, I., Shankar, S. (2018). Case of keratoacanthoma centrifugum marginatum treated with acitretin. BMJ Case Rep. Nov 01.
  • Molz, P., & Schröder, N. (2017). Potential therapeutic effects of lipoic acid on memory deficits related to aging and neurodegeneration. Frontiers in pharmacology, 8, 849.
  • Nomura, M., Sumiya, R., Ono, H. et al. (2021).Cessation of methotrexate and a small intestinal resection provide a good clinical course for a patient with a jejunum perforation induced by amethotrexate-associated lymphoproliferative disorder: a case report. World J Surg Onc 19, 4. https://doi.org/10.1186/s12957-020-02114-0
  • Ortiz, N. E. G., Nijhawan, R.I., Weinberg, J. M. (2013). Acitretin. Dermatol Ther, 26(5), 390-9.
  • Packer, L., Cadenas, E. (2011). Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr. 48(1), 26-32.
  • Reed L. J. (1998). From lipoic acid to multi-enzyme complexes. Protein Sci. 7, 220–224. 10.1002/pro.5560070125.
  • Rudrapal, M., Shubham, J., Kha, K. J., Dukhyil, A. B., Ansari, M.A., Alomar, M. N., Fahad M., Alshabrmi, F. M., Palai S., Prashanta Kumar Deb, P.K., Devi ajlakshmi Devi. (2022). Dietary polyphenols and their role in oxidative stress-ınduced human diseases: Insights Into protective effects, antioxidant potentials and mechanism(s) of action. Front Pharmacol. 14(13), 806470.
  • Shay, K. P., Moreau, R. F., Smith, E. J., Smith, A. R., Hagen, T. M. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim. Biophys. Acta 1790, 1149 1160. doi: 10.1016/j.bbagen.2009.07.026
  • Sadowska, M., Garbutt, J., Lesiak, A. (2022). Pros and cons of using systemic acitretin in the paediatric population. Postepy Dermatol Alergol. 39(1):34-38.
  • Schmidt, A.M., Hori, O., Brett, J., Yan, S.D., Wautier, J.L., Stern, D. (1994). Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler. Thromb. 14, 1521–1528.
  • Sezgin, F.G., Dıraman, E. & İncilay Torunoğlu, E. (2022). Rat Beyin Dokusunda Asitretin –Metotreksat Kombinasyonunun ve Α-Lipolik Asit’in Polifenol Oksidaz Aktivitesi Üzerine Etkileri. European Journal of Science and Technology, (37), 165-169.
  • Shiga, S., Machida, T., Yanada, T., Machida, M., Hirafuji, M., Iizuka, K. (2020). The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats. Journal of Pharmacological Sciences. 143, 1, 30-38.
  • Skillen, L.A, Corry, A. (2019). Combination therapy of sirolimus and acitretin in solid organ transplant recipients: a new cutaneous adverse event. Clin Exp Dermatol. 44(1):62-63.
  • Steffens, J.C, Harel, E, Hunt, M.D. (1994) Polyphenol oxidase. In BE Ellis, ed, Genetic Engineering of Plant Secondary Metabolism. Plenum Press, New York, pp 275–312.
  • Vallianou, N., Evangelopoulos, A., Koutalas, P. (2009). Alpha-lipoic Acid and diabetic neuropathy.Rev Diabet Stud. Winter 6(4), 230-6.
  • Wang, Y.H., Tsai, D. (2014). Small intestine perforation in a 58-year-old man with Darier disease after 25 months of oral acitretin therapy. Dermatologica Sinica. 32, 39-42.
  • Weinblatt, M.E, Coblyn, J.S., Fox, D.A., Fraser, P.A., Holdsworth, D.E., Glass, D.N., TrenthamD.E. (1985). Efficacy of low-dose methotrexate in rheumatoid arthritis. N. Engl. J. Med.28;312(13):818-822.
  • Zito, P.M, Mazzoni, T. (2022). Acitretin. In: StatPearls [Internet]. Treasure Island (FL): Stat Pearls Publishing; Sep 25.
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Fatma Gönül Solmaz 0000-0002-9400-5173

Emine İncilay Torunoğlu 0000-0003-4641-0067

Emine Dıraman 0000-0002-4677-1738

Proje Numarası PYO.FEN.1904.18.014
Yayımlanma Tarihi 30 Aralık 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 1 Sayı: 3

Kaynak Göster

APA Solmaz, F. G., Torunoğlu, E. İ., & Dıraman, E. (2022). Effects of Alpha-Lipoic Acid On Polyphenol Oxidase Activity in Small Intestine Tissue of Rats Treated With Acitretin - Methotrexate Combination. Doğu Karadeniz Sağlık Bilimleri Dergisi, 1(3), 28-37.

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