Ülseratif Kolit Oluşturulan Hayvan Modelinde Arum Dioscoridis Bitki Ekstraktı Uygulamasının Antioksidan ve Anti-inflamatuvar Etkisi
Yıl 2022,
Cilt: 17 Sayı: 1, 172 - 181, 21.03.2022
Ahmet Burak Ağaoğlu
,
Kadir Gişi
,
Murat İspiroğlu
,
Abdulkadir Yasir Bahar
Fatma İnanç Tolun
,
Bülent Kantarçeken
Öz
Amaç
Arum dioscoridis ülkemizde yetişen oksidasyon, immün sistem, inflamasyon üzerine birçok biyolojik aktiviteyi düzenlediği gösterilmiş bir bitkidir. Bizde çalışmamızda farelerde asetik asit ile oluşturulan deneysel kolitte arum dioscoridisin etkilerini araştırmayı amaçladık.
Gereç ve yöntemler
Ağırlıkları 180-210 gr arasında değişen 6 haftalık 56 adet Wistar Albino cinsi dişi sıçanlar her grupta 8 hayvan olacak şekilde 7 eşit gruba ayrıldı.Grup 1; kontrol grubu. Grup 2 deneysel kolit oluşturulan grup. Grup 3 profilaktik oral arum dioscoridis tedavisi verilerek deneysel kolit oluşturulan grup. Grup 4 deneysel kolit oluşturulan ve etanollü çözücüyle oral arum dioscoridis tedavisi verilen grup. Grup 5 deneysel kolit oluşturulan ve DMSO (Dimetil sülfoksit)’lu çözücüyle oral tedavi verilen grup. Grup 6 deneysel kolit oluşturulan ve DMSO’lu çözücüyle rektal tedavi verilen grup. Grup 7 deneysel kolit oluşturulan ve 2 kat oral tedavi verilen grup. Farelerden alınan doku örneklerinde arum dioscoridisin etkileri makroskopik,histopatolojik ve biyokimyasal olarak değerlendirildi.
Bulgular
Kolit grubunda tedavi gruplarına göre önemli kilo kaybı meydana geldi. Arum dioscoridis tedavisi ve profilaksisi ile makroskopik ve mikroskobik analizde istatistiksel olarak anlamlı iyileşme bulundu. Asetik asit ile oluşturulan kolit modelinde toplam oksidan durum, tiyol/disülfid, malondialdehit, miyeloperoksidaz seviyelerinde artış ve toplam antioksidan kapasitede azalma tespit edildi.
Sonuç
Bu çalışma, arum dioscoridis'in ratlarda oluşturulan kolit modelinde olumlu etkileri olduğunu ve özellikle etanol ile eritilerek verilen ve profilaksi amaçlı kullanılan gruplarda barsak iltihabını önemli ölçüde iyileştirdiğini göstermiştir.
Destekleyen Kurum
Scientific Research Projects Unit of Kahramanmaras Sutcu Imam University
Proje Numarası
2019/4-19D
Teşekkür
Kahramanmaraş Sütçü İmam Üniversitesi Bilimsel Araştırma Projeleri Birimi'ne bu araştırma projesine verdikleri maddi desteklerinden dolayı teşekkür eder ve takdirlerimi sunarım.
Kaynakça
- Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol E, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0.
- Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am. 2015;95(6):1105-v. doi:10.1016/j.suc.2015.07.006 Macdermott, R. P., & Green, J. A. (2007). Refractory ulcerative colitis treatment. Gastroenterology & hepatology, 3(1), 64–69.
- Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, et al. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis. 2015;9(1):86-106. doi:10.1093/ecco-jcc/jju007.
- Amirshahrokhi K. Febuxostat attenuates ulcerative colitis by the inhibition of NF-κB, proinflammatory cytokines, and oxidative stress in mice. Int Immunopharmacol. 2019;76:105884. doi:10.1016/j.intimp.2019.105884.
- Goudarzi R, Partoazar A, Mumtaz F, Yousefi-Manesh H, Abdollahi A, Dehpour A, et al. Arthrocen, an avocado-soy unsaponifiable agent, improves acetic acid-induced colitis in rat by inhibition of NF-kB signaling pathway. J Food Biochem. 2020;44(7):e13244. doi:10.1111/jfbc.13244
- Adjouzem CF, Gilbert A, Mbiantcha M, Yousseu Nana W, Matah Marthe Mba V, Djuichou Nguemnang SF, et al. Effects of Aqueous and Methanolic Extracts of Stem Bark of Alstonia boonei De Wild. (Apocynaceae) on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Wistar Rats. Evid Based Complement Alternat Med. 2020;2020:4918453. doi:10.1155/2020/4918453
- Arya VS, Kanthlal SK. Phloretin Ameliorates Acetic Acid induced Colitis through Modulation of Immune and Inflammatory Reactions in Rats. Endocr Metab Immune Disord Drug Targets. 2021;21(1):163-172. doi: 10.2174/1871530320666200624120257.
- Karahan F, Kulak M, Urlu E, Gözüacik HG, Böyümez T, Şekeroğlu N, et al (2015). Total Phenolic Content, Ferric Reducing and DPPH Scavenging Activity of Arum dioscoridis. Nat Prod Res. 2015;29(17):1678-1683. doi:10.1080/14786419.2014.991320
- MacPherson B, Pfeiffer CJ. Experimental colitis. Digestion. 1976;14(5-6):424-452.
- Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96(3):795-803.
- Erben U, Loddenkemper C, Doerfel K, Spieckermann S, Haller D, Heimesaat MM, et al. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Clin Exp Pathol. 2014;7(8):4557–4576.
- Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10. doi: 10.1016/s0076-6879(78)52032-6.
- Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78(3):206–9.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. PMID: 14907713.
- Panés J, Alfaro I. New treatment strategies for ulcerative colitis. Expert Rev Clin Immunol. 2017;13(10):963-973. doi:10.1080/1744666X.2017.1343668
- Eder P, Korybalska K, Linke K, Witowski J. Angiogenesis-related proteins--their role in the pathogenesis and treatment of inflammatory bowel disease. Curr Protein Pept Sci. 2015;16(3):249-258.
- Fabia R, Willén R, Ar'Rajab A, Andersson R, Ahrén B, Bengmark S. Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. Eur Surg Res. 1992;24(4):211-225. doi:10.1159/000129209.
- Yamada Y, Marshall S, Specian RD, Grisham MB. A comparative analysis of two models of colitis in rats. Gastroenterology. 1992;102(5):1524-1534. doi:10.1016/0016-5085(92)91710-l.
- Rezayat SM, Dehpour AR, Motamed SM, Yazdanparast M, Chamanara M, Sahebgharani M, et al. Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway. Inflammopharmacology, 26(3), 851–859. doi:10.1007/s10787-017-0409-1
- Rocha J, Direito R, Lima A, Mota J, Gonçalves M, Duarte MP, et al. Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in mice. Biomed Pharmacother. 2019;118:109351. doi:10.1016/j.biopha.2019.109351
- Farooq SM, Hou Y, Li H, O'Meara M, Wang Y, Li C, et al. Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice. Dig Dis Sci. 2018;63(11):2910-2922. doi.org/10.1007/s10620-018-5216-z
- Tatiya-Aphiradee N, Chatuphonprasert W, Jarukamjorn K. Immune response and inflammatory pathway of ulcerative colitis. J Basic Clin Physiol Pharmacol. 2018;30(1):1-10. doi:10.1515/jbcpp-2018-0036
- MacPherson BR, Pfeiffer CJ. Experimental production of diffuse colitis in rats. Digestion. 1978;17(2):135–150. doi:10.1159/000198104.
- Johnson TO, Odoh KD, Nwonuma CO, Akinsanmi AO, Adegboyega AE. Biochemical evaluation and molecular docking assessment of the anti-inflammatory potential of Phyllanthus nivosus leaf against ulcerative colitis. Heliyon. 2020;6(5):e03893. doi:10.1016/j.heliyon.2020.e03893
Yabalak E. Radical scavenging activity and chemical composition of methanolic extract from Arum dioscoridis SM. var. dioscoridis and determination of ıts mineral and trace elements. JOTCSA. 5(1): 205-218, 2018. doi:10.18596/jotcsa.350370
- Uğuzlar H, Maltas E, Yıldız S. Screening of phytochemicals and antioxidant activity of Arum dioscoridis seeds. Journal of Food Biochemistry. 2012; 36 (3): 285–291.
- Uçan Türkmen F , Mercımek Takcı H , Sarıgullu Onalan F , Saglam H . Arum dioscoridis Ekstraktlarının Toplam Fenolik, Flavonoid İçerikleri ile Antioksidan ve Antibakteriyel Aktivitelerinin Araştırılması. Harran Üniversitesi Mühendislik Dergisi. 2019; 4(1): 102-108.
- Öztürk E, Ozcimen A, & Çelik H. (2017). Anti-Metastatic Effect of Arum dioscoridis with Tozasertib in CFPAC-1 Pancreas Carcinoma Cell Line.
- Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277–85.
- Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-1111. doi:10.1016/j.clinbiochem.2005.08.008.
- Mouzaoui S, Banerjee S, Djerdjouri B. Low-dose curcumin reduced TNBS-associated mucin depleted foci in mice by scavenging superoxide anion and lipid peroxides, rebalancing matrix NO synthase and aconitase activities, and recoupling mitochondria. Inflammopharmacology. 2020 Aug;28(4):949-965. doi: 10.1007/s10787-019-00684-4.
- Hsu JL, Chou JW, Chen TF, Hsu JT, Su FY, Lan JL, et al. Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis. EMBO Mol Med. 2020;12(1):e9386. doi:10.15252/emmm.201809386
- Yorulmaz E, Yorulmaz H, Gökmen ES, Altınay S, Küçük SH, Zengi O, et al. Therapeutic effectiveness of rectally administered fish oil and mesalazine in trinitrobenzenesulfonic acid-induced colitis. Biomed Pharmacother. 2019;118:109247. doi:10.1016/j.biopha.2019.109247
- Gęgotek A, Skrzydlewska E. Biological effect of protein modifications by lipid peroxidation products. Chem Phys Lipids. 2019;221:46-52. doi:10.1016/j.chemphyslip.2019.03.011
Güvenç M, Cellat M, Özkan H, Tekeli İO, Uyar A, Gökçek İ, et al. Protective Effects of Tyrosol Against DSS-Induced Ulcerative Colitis in Rats. Inflammation. 2019;42(5):1680–1691. doi:10.1007/s10753-019-01028-8
- Da Silva S, Keita ÅV, Mohlin S, Påhlman S, Theodorou V, Påhlman I, et al. A Novel Topical PPARγ Agonist Induces PPARγ Activity in Ulcerative Colitis Mucosa and Prevents and Reverses Inflammation in Induced Colitis Models. Inflamm Bowel Dis. 2018;24(4):792–805. doi:10.1093/ibd/izx079
- Neselioglu S, Keske PB, Senat AA, Yurekli OT, Erdogan S, Alisik M, et al. The relationship between severity of ulcerative colitis and thiol-disulphide homeostasis. Bratisl Lek Listy. 2018;119(8):498-502. doi: 10.4149/BLL_2018_091.
- Karimi S, Tabataba-Vakili S, Yari Z, Alborzi F, Hedayati M, Ebrahimi-Daryani N, et al. The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status. Nutr J. 2019 Mar 11;18(1):16. doi: 10.1186/s12937-019-0441-7.
Intestinal Anti-Inflammatory and Anti-Oxidant Activity of The Aqueous Extract From Arum Dioscoridis in Acetic Acid Induced Colitis in Rats
Yıl 2022,
Cilt: 17 Sayı: 1, 172 - 181, 21.03.2022
Ahmet Burak Ağaoğlu
,
Kadir Gişi
,
Murat İspiroğlu
,
Abdulkadir Yasir Bahar
Fatma İnanç Tolun
,
Bülent Kantarçeken
Öz
Objective
Arum dioscoridis is a plant that has been shown to regulate biological activity on oxidation, immune system and inflammation grown in our country. We aimed to investigate the effects of arum dioscoridis in experimental colitis related to acetic acid in rats.
Material and Methods
In this study 56 Wistar Albino female rats, 6 weeks old, weighing 180- 210 g, were seperated into 7 equal groups with 8 animals in each group. Group 1 is the control one without any administration. An experimental colitis has been created on Group 2. Group 3 is treated with prophylactic oral arum dioscoridis before creating experimental colitis. The rats belongs to Group 4 has been received oral arum dioscoridis treatment with ethanolic solvent after creating experimental colitis. Group 5 was given oral treatment with solvent with DMSO (Dimethyl sulfoxide) after experimental colitis was created. Group 6 rectal treatment with solvent with DMSO after experimental colitis has been created. Group 7 was given a 2-fold oral treatment after experimental colitis. In tissue samples taken from mice, the effects of arum dioscoridis were evaluated macroscopically, histopathologically and biochemically.
Results
In the colitis group, significant weight loss occurred compared to the treatment groups. Statistically significant improvement was found in macroscopic and microscopic analysis with arum dioscoridis treatment and prophylaxis. In the colitis model which is created with acetic acid, total oxidant status, thiol / disulfide, malondialdehyde, myeloperoxidase levels increased and a decrease in total antioxidant capacity was detected.
Conclusion
This study showed that arum dioscoridis has positive effects on the colitis model created in rats, and it significantly improves intestinal inflammation especially in groups given by dissolving with ethanol and used for prophylaxis purposes
Proje Numarası
2019/4-19D
Kaynakça
- Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol E, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0.
- Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am. 2015;95(6):1105-v. doi:10.1016/j.suc.2015.07.006 Macdermott, R. P., & Green, J. A. (2007). Refractory ulcerative colitis treatment. Gastroenterology & hepatology, 3(1), 64–69.
- Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, et al. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis. 2015;9(1):86-106. doi:10.1093/ecco-jcc/jju007.
- Amirshahrokhi K. Febuxostat attenuates ulcerative colitis by the inhibition of NF-κB, proinflammatory cytokines, and oxidative stress in mice. Int Immunopharmacol. 2019;76:105884. doi:10.1016/j.intimp.2019.105884.
- Goudarzi R, Partoazar A, Mumtaz F, Yousefi-Manesh H, Abdollahi A, Dehpour A, et al. Arthrocen, an avocado-soy unsaponifiable agent, improves acetic acid-induced colitis in rat by inhibition of NF-kB signaling pathway. J Food Biochem. 2020;44(7):e13244. doi:10.1111/jfbc.13244
- Adjouzem CF, Gilbert A, Mbiantcha M, Yousseu Nana W, Matah Marthe Mba V, Djuichou Nguemnang SF, et al. Effects of Aqueous and Methanolic Extracts of Stem Bark of Alstonia boonei De Wild. (Apocynaceae) on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Wistar Rats. Evid Based Complement Alternat Med. 2020;2020:4918453. doi:10.1155/2020/4918453
- Arya VS, Kanthlal SK. Phloretin Ameliorates Acetic Acid induced Colitis through Modulation of Immune and Inflammatory Reactions in Rats. Endocr Metab Immune Disord Drug Targets. 2021;21(1):163-172. doi: 10.2174/1871530320666200624120257.
- Karahan F, Kulak M, Urlu E, Gözüacik HG, Böyümez T, Şekeroğlu N, et al (2015). Total Phenolic Content, Ferric Reducing and DPPH Scavenging Activity of Arum dioscoridis. Nat Prod Res. 2015;29(17):1678-1683. doi:10.1080/14786419.2014.991320
- MacPherson B, Pfeiffer CJ. Experimental colitis. Digestion. 1976;14(5-6):424-452.
- Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96(3):795-803.
- Erben U, Loddenkemper C, Doerfel K, Spieckermann S, Haller D, Heimesaat MM, et al. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Clin Exp Pathol. 2014;7(8):4557–4576.
- Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10. doi: 10.1016/s0076-6879(78)52032-6.
- Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78(3):206–9.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. PMID: 14907713.
- Panés J, Alfaro I. New treatment strategies for ulcerative colitis. Expert Rev Clin Immunol. 2017;13(10):963-973. doi:10.1080/1744666X.2017.1343668
- Eder P, Korybalska K, Linke K, Witowski J. Angiogenesis-related proteins--their role in the pathogenesis and treatment of inflammatory bowel disease. Curr Protein Pept Sci. 2015;16(3):249-258.
- Fabia R, Willén R, Ar'Rajab A, Andersson R, Ahrén B, Bengmark S. Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. Eur Surg Res. 1992;24(4):211-225. doi:10.1159/000129209.
- Yamada Y, Marshall S, Specian RD, Grisham MB. A comparative analysis of two models of colitis in rats. Gastroenterology. 1992;102(5):1524-1534. doi:10.1016/0016-5085(92)91710-l.
- Rezayat SM, Dehpour AR, Motamed SM, Yazdanparast M, Chamanara M, Sahebgharani M, et al. Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway. Inflammopharmacology, 26(3), 851–859. doi:10.1007/s10787-017-0409-1
- Rocha J, Direito R, Lima A, Mota J, Gonçalves M, Duarte MP, et al. Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in mice. Biomed Pharmacother. 2019;118:109351. doi:10.1016/j.biopha.2019.109351
- Farooq SM, Hou Y, Li H, O'Meara M, Wang Y, Li C, et al. Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice. Dig Dis Sci. 2018;63(11):2910-2922. doi.org/10.1007/s10620-018-5216-z
- Tatiya-Aphiradee N, Chatuphonprasert W, Jarukamjorn K. Immune response and inflammatory pathway of ulcerative colitis. J Basic Clin Physiol Pharmacol. 2018;30(1):1-10. doi:10.1515/jbcpp-2018-0036
- MacPherson BR, Pfeiffer CJ. Experimental production of diffuse colitis in rats. Digestion. 1978;17(2):135–150. doi:10.1159/000198104.
- Johnson TO, Odoh KD, Nwonuma CO, Akinsanmi AO, Adegboyega AE. Biochemical evaluation and molecular docking assessment of the anti-inflammatory potential of Phyllanthus nivosus leaf against ulcerative colitis. Heliyon. 2020;6(5):e03893. doi:10.1016/j.heliyon.2020.e03893
Yabalak E. Radical scavenging activity and chemical composition of methanolic extract from Arum dioscoridis SM. var. dioscoridis and determination of ıts mineral and trace elements. JOTCSA. 5(1): 205-218, 2018. doi:10.18596/jotcsa.350370
- Uğuzlar H, Maltas E, Yıldız S. Screening of phytochemicals and antioxidant activity of Arum dioscoridis seeds. Journal of Food Biochemistry. 2012; 36 (3): 285–291.
- Uçan Türkmen F , Mercımek Takcı H , Sarıgullu Onalan F , Saglam H . Arum dioscoridis Ekstraktlarının Toplam Fenolik, Flavonoid İçerikleri ile Antioksidan ve Antibakteriyel Aktivitelerinin Araştırılması. Harran Üniversitesi Mühendislik Dergisi. 2019; 4(1): 102-108.
- Öztürk E, Ozcimen A, & Çelik H. (2017). Anti-Metastatic Effect of Arum dioscoridis with Tozasertib in CFPAC-1 Pancreas Carcinoma Cell Line.
- Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277–85.
- Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-1111. doi:10.1016/j.clinbiochem.2005.08.008.
- Mouzaoui S, Banerjee S, Djerdjouri B. Low-dose curcumin reduced TNBS-associated mucin depleted foci in mice by scavenging superoxide anion and lipid peroxides, rebalancing matrix NO synthase and aconitase activities, and recoupling mitochondria. Inflammopharmacology. 2020 Aug;28(4):949-965. doi: 10.1007/s10787-019-00684-4.
- Hsu JL, Chou JW, Chen TF, Hsu JT, Su FY, Lan JL, et al. Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis. EMBO Mol Med. 2020;12(1):e9386. doi:10.15252/emmm.201809386
- Yorulmaz E, Yorulmaz H, Gökmen ES, Altınay S, Küçük SH, Zengi O, et al. Therapeutic effectiveness of rectally administered fish oil and mesalazine in trinitrobenzenesulfonic acid-induced colitis. Biomed Pharmacother. 2019;118:109247. doi:10.1016/j.biopha.2019.109247
- Gęgotek A, Skrzydlewska E. Biological effect of protein modifications by lipid peroxidation products. Chem Phys Lipids. 2019;221:46-52. doi:10.1016/j.chemphyslip.2019.03.011
Güvenç M, Cellat M, Özkan H, Tekeli İO, Uyar A, Gökçek İ, et al. Protective Effects of Tyrosol Against DSS-Induced Ulcerative Colitis in Rats. Inflammation. 2019;42(5):1680–1691. doi:10.1007/s10753-019-01028-8
- Da Silva S, Keita ÅV, Mohlin S, Påhlman S, Theodorou V, Påhlman I, et al. A Novel Topical PPARγ Agonist Induces PPARγ Activity in Ulcerative Colitis Mucosa and Prevents and Reverses Inflammation in Induced Colitis Models. Inflamm Bowel Dis. 2018;24(4):792–805. doi:10.1093/ibd/izx079
- Neselioglu S, Keske PB, Senat AA, Yurekli OT, Erdogan S, Alisik M, et al. The relationship between severity of ulcerative colitis and thiol-disulphide homeostasis. Bratisl Lek Listy. 2018;119(8):498-502. doi: 10.4149/BLL_2018_091.
- Karimi S, Tabataba-Vakili S, Yari Z, Alborzi F, Hedayati M, Ebrahimi-Daryani N, et al. The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status. Nutr J. 2019 Mar 11;18(1):16. doi: 10.1186/s12937-019-0441-7.