The Effects of Acetretin-Methotrexate Combination and Α-Lipolic Acid on Polyphenol Oxidase Activity in Rat Brain Tissue

Öz

In this study, the effects of acitretin (ACT) and methotrexate (MTX) active ingredients and alpha lipoic acid (ALA) on Polyphenol Oxidase (PO) activity in rat brain tissue were investigated. A total of 50 Wistar albino male rats were used in the study. Study groups were formed as Control group (K), ALA group, ACT+MTX group and ACT+MTX+ALA group. Injections made to rats that were fasted for 24 hours were performed at the same time each morning. ACT, MTX and ALA were dissolved in 0.9% NaCl. ACT (20mg/kg/day), MTX (20mg/kg/week), ALA (50mg/kg/day) and their combinations were given to the rats by intraperitoneal injection at body weight level. Rats were sacrificed by cervical dislocation and their brains were removed after cardiac perfusion. PO enzyme activity was measured in brain tissue samples taken from rats. While In the group given ACT+MTX, approximately 5% inhibition was observed on the 3rd day compared to K, this inhibition was replaced by activation with the effect of ALA. While the use of ACT + MTX caused inhibition in brain PO activity on the 3rd day, this inhibition turned into activation in the following days. When the group given ALA alone was compared with the K group; PO activity showed 7% inhibition on 3rd day. It was observed that this inhibition level decreased by half on the 5th and 7th days. Thus, as a result of our study, it can be said that ALA has an antioxidant effect in the brain tissue.

Anahtar Kelimeler

• Brain,
• Acitretin,
• Methotrexate
• Polyphenol oxidase

Rat Beyin Dokusunda Asitretin - Metotreksat Kombinasyonunun ve Α-Lipolik Asit’in Polifenol Oksidaz Aktivitesi Üzerine Etkileri

Öz

Bu çalışmada asitretin (ACT) ve metotreksat (MTX) etken maddelerinin ve alfa lipoik asitin (ALA) rat beyin dokusunda Polifenol Oksidaz (PO) aktivitesine etkileri araştırılmıştır. Çalışmada, toplam 50 tane Wistar albino erkek rat kullanılmıştır. Çalışma grupları, Kontrol grubu (K), ALA grubu, ACT+MTX grubu ve ACT+MTX+ALA grubu olarak oluşturulmuştur. 24 saat aç bırakılmış olan ratlara yapılan enjeksiyon işlemleri her sabah aynı saatte gerçekleştirilmiştir. ACT, MTX ve ALA % 0.9’luk NaCl’de çözülmüştür. ACT (20mg/kg/gün), MTX (20mg/kg/hafta), ALA (50mg/kg/gün) ve bunların kombinasyonları da vücut ağırlığı düzeyinde intraperitonal enjeksiyon ile ratlara verilmiştir. Ratlar servikal dislokasyon ile sakrifiye edilmiş ve kalp perfüzyonundan sonra beyinleri çıkarılmıştır. Ratlardan alınan beyin doku örneklerinde, PO enzim aktivitesi ölçülmüştür. ACT+MTX verilen grupta 3. günde K’ya göre yaklaşık % 5 inhibisyon gözlenirken ALA’nın etkisi ile bu inhibisyon yerini aktivasyona bırakmıştır. ACT + MTX kullanımı beyin PO aktivitesinde 3. günde inhibisyona neden olurken bu inhibisyon ilerleyen günlerde aktivasyona dönüşmüştür. Tek başına ALA verilen grup K grubu ile karşılaştırıldığında; PO aktivitesi 3. günde %7 inhibisyon göstermiştir. 5. ve 7.günlerde inhibisyon seviyesinin yarı yarıya azaldığı gözlenmiştir. Böylece çalışmamızın sonucu olarak ALA’nın beyin dokusunda antioksidan etki gösterdiği söylenebilir.

Anahtar Kelimeler

• Beyin,
• Asitretin,
• Metotreksat,
• Polifenol oksidaz

Kaynakça

1. 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 121:158-168
2. 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 (2020) 1(1):19-22
3. Bhuiyan, Z.H., Chowdhury, M.,K. (2016). Acitretin in dermatology a review. Bangladesh Med J 45(2): 98-100
4. Data, P. (1995). Alpha-lipoic acid. Arzneimittelforschung, 45, 872-874.
5. Dogra, S., & Yadav, S. (2014). Acitretin in psoriasis: an evolving scenario. International journal of dermatology, 53(5), 525–538. https://doi.org/10.1111/ijd.12365.
6. Gorąca, A., Huk-Kolega, H., Piechota, A., Kleniewska, P., Ciejka, E., & Skibska, B. (2011). Lipoic acid-biological activity and therapeutic potential. Pharmacological Reports, 63(4), 849-858.
7. Head, E., Nukala, V., Fenoglio, K., Muggenburg, B., Cotman, C., & Sullivan, P. (2009). Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging. Experimental neurology, 220(1), 171-176.
8. 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.

9. Hung SY, Boucias DG (1996). Phenoloxidase activity in the hemolymph of naive and Beauvaria bassianainfected Spodoptera exigua larvae. J Invert Pathol 67:35-40
10. Kumar, K., H., Khanum, F., (2013). Hydroalcoholic Extract of Cyperus rotundus Ameliorates H2O2-Induced Human Neuronal Cell Damage via Its Anti-oxidative and Anti-apoptotic Machinery. Cell Mol Neurobiol (2013) 33:5–17
11. Kumari, S., Kumari, S., Sharma, A. K., & Kaur, I. (2016). Methotrexate induced hepatotoxicity and its management. Inter J Sci Res, 5, 1477-1481.
12. 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.
13. Menter, A., Gottlieb, A., Feldman, S. R., Van Voorhees, A. S., Leonardi, C. L., Gordon, K. B., Lebwohl, M., Koo, J. Y., Elmets, C. A., & Korman, N. J. (2008).
14. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. Journal of the American Academy of Dermatology, 58(5), 826-850.
15. Patel, M. S., & Roche, T. E. (1990). Molecular biology and biochemistry of pyruvate dehydrogenase complexes 1. The FASEB Journal, 4(14), 3224-3233.
16. Rochette, L., Ghibu, S., Richard, C., Zeller, M., Cottin, Y., & Vergely, C. (2013). Direct and indirect antioxidant properties of α‐lipoic acid and therapeutic potential. Molecular nutrition & food research, 57(1), 114-125.
17. Tetikçok, R., Özçetin, M., ÇELTEK, N. Y., Oktay, G., Ufuk, Ü., & Şengül, M. (2015). Lıpoıc Acıd. Çağdaş Tıp Dergisi, 5(3), 206-209.Data, P. (1995). Alpha-lipoic acid. Arzneimittelforschung, 45, 872-874.
18. Vardi, N., Parlakpinar, H., Ates, B., & Otlu, A. (2010). Metotreksatin Neden Oldugu Testiküler Hasara Karsi Klorogenik Asidin Koruyucu Etkileri/The Preventive Effects of Chlorogenic Acid Against to Testicular Damage Caused by Methotrexate. Türkiye Klinikleri. Tip Bilimleri Dergisi, 30(2), 507.
19. Whitaker JR (1995). Polyphenol oxidase. In: Wong DWS, In: food ezymes: structure and mechanism. pp. 271-307 New York: Chapman and Hall, 1995
20. Yamauchi, P. S., Rizk, D., Kormeili, T., Patnaik, R., & Lowe, N. J. (2003). Current systemic therapies for psoriasis: where are we now? Journal of the American Academy of Dermatology, 49(2), 66-77.