The effect of the application of alpha lipoic acid, acitretin + methotrexate and alpha lipoic acid + acitretin + methotrexate on the levels of malondialdehyde in the kidney tissues of rats

Abstract

Acitretin (ACT), which is a second generation retinoid, exerts a therapeutic effect. It also has an anti-inflammatory and antiproliferative effect. It can also be used alone or in combination in the treatment of some diseases. In the use of methotrexate (MTX) alone, it can cause serious side effects such as hepotoxicity and nephrotoxicity; As a result of its use with ACT in recent years, it has been shown to have side effects on some organs as well as being beneficial. In this study, the effects of MTX, ACT and ALA on malondialdehyde (MDA) levels in rat kidney tissue were investigated. For this purpose, rats were given ALA, ACT + MTX and ACT + MTX + ALA by intraperitoneal injection. Following this, after the injections on the 3rd, 5th and 7th days, the kidneys were removed by applying cervical dislocation to the rats. The kidneys were homogenized, sonified and centrifuged. The fractions obtained as a result of these processes were used to investigate the effects on malondialdehyde (MDA) levels. As a result, when compared to the MDA levels in the control group, an overall increase was observed in the group given MTX + ACT. It was determined that the increase continued with the administration of ALA with MTX + ACT. Only in the group where ALA was given, a decrease in MDA level was observed.

Keywords

• Malondialdehyde,acitretin,methotrexate,alpha lipoic acid,kidney

References

1. Aksoy, M (2017) Prepubertal sıçanlarda busulfan ile oluşturulan testis hasarına alfa lipoik asitin etkisi. Yüksek lisans tezi, Dokuz Eylül Üniversitesi Tıp Fakültesi Histoloji ve Embriyoloji Anabilimdalı, Narlıdere, İzmir
2. Ali, N., Rashid, S., Nafees, S., Hasan, S. K., Shahid, A., Majed, F., & Sultana, S (2017) Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: An experimental approach. Chemico-biological interactions, 272, 80-91
3. Alinejad, A., Akbari, H., Ghaderpoori, M., Jeihooni, A. K., & Adibzadeh, A (2019) Catalytic ozonation process using a MgO nano-catalyst to degrade methotrexate from aqueous solutions and cytotoxicity studies in human lung epithelial cells (A549) after treatment. RSC advances, 9(15), 8204-8214
4. 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. Pharmacological research, 121, 158-168
5. Armağan, İ (2015) Metotreksat'ın Karaciğer ve Böbrekte Neden Olduğu Hasarda Oksidatif Stresin Rolü. SDÜ Tıp Fakültesi Dergisi, 22(4)
6. Armagan, I., Bayram, D., Candan, I. A., Yigit, A., Celik, E., Armagan, H. H., & Uğuz, A. C (2015) Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats. Environmental toxicology and pharmacology, 39(3), 1122-1131
7. Bludovska, M., Kotyzova, D., Koutensky, J., & Eybl, V (1999) The influence of-lipoic acid on the toxicity of cadmium. Gen. Physiol. Biophys, 18, 28-32
8. Cadenas, E (2001) Handbook of antioxidants (2nd ed). Marcel Dekker Incorporated, Newyork; 23:473

9. Chabner, B., Wilson, W. and Supko, J (2007) Pharmacology and toxicity of antineoplastic drugs. Editorial: Lichtman MA, Beutler E, Seligsohn U, Kipps TJ, Kaushansky K. Williams Hematology. 7th Edition. Mc Graw Hill Company, United States, 249
10. Cui, X., Zuo, P., Zhang, Q., Li, X., Hu, Y., Long, J., Liu, J (2006) Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic acid. J Neurosci Res, 83(8), 1584-1590. doi: 10.1002/jnr.20845
11. Draper, H. H., & Hadley, M (1990) Malondialdehyde determination as index of lipid Peroxidation. In Methods in enzymology (Vol. 186, pp. 421-431). Academic press
12. Ergene, E (2018) Alfa lipoik asit ve metabolik etkileri üzerine bir araştirma. Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 2(3), 159-165
13. Gedik D (2019) Metotreksatin neden olduğu hepatotoksisitede luteolinin etksinin değerlendirilmesi Yüksek lisans tezi, Erciyes Üniversitesi, Sağlık Bilimleri Enstitüsü Tıbbi Farmakoloji Anabilim Dalı Kayseri
14. Gomes, M. B., & Negrato, C. A (2014) Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetology & metabolic syndrome, 6(1), 80
15. Güven, E., Erişgin, Z., & Tekelioğlu, Y (2017) Siçanlarda metotreksat kaynakli testis hasari üzerine shilajitin’in histopatolojik etkisi. Kocatepe Tıp Dergisi, 18(1), 1-6
16. Khalil, S., Bardawil, T., Stephan, C., Darwiche, N., Abbas, O., Kibbi, A. G., ... & Kurban, M (2017) Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects. Journal of Dermatological Treatment, 28(8), 684-696
17. 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
18. Kilic, F., Handelman, G. J., Traber, K., Tsang, K., Packer, L., & Trevithick, J. R (1998) Modelling cortical cataractogenesis XX. In vitro effect of alpha-lipoic acid on glutathione concentrations in lens in model diabetic cataractogenesis. Biochem Mol Biol Int, 46(3), 585-595
19. Lowenthal, K. E., Horn, P. J., & Kalb, R. E (2008) Concurrent use of methotrexate and acitretin revisited. Journal of dermatological treatment, 19(1), 22-26
20. Maritim, A. C., Sanders, R. A., & Watkins Iii, J. B (2003) Effects of α-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. The Journal of nutritional biochemistry, 14(5), 288-294
21. Özarmagan, G (2016) Sistemik retinoidler. Turkderm, 50, 24.
22. Ozgun, E., Ozgun, G. S., Usta, U., Eskiocak, S., Sut, N., & Gokmen, S. S (2018) The effect of lipoic acid in the prevention of myocardial infarction in diabetic rats. Bratislavske lekarske listy, 119(10), 664-669
23. Sentürk, N (2016). METOTREKSAT. Turkderm, 50, 20.
24. Tetikçok, R., Özçetin, M., Çeltek, N. Y., Oktay, G., Ünlü, U., ve Şengül, M (2015) Lipoik asit. Journal of Contemporary Medicine, 5(3), 206-209
25. Tu, J., Yin, Z., Guo, J., He, F., Long, F., & Yin, Z (2020) Acitretin inhibits IL-17 A-induced IL- 36 expression in keratinocytes by down-regulating IκBζ. InternationaI Immunopharmacology, 79, 106045
26. Uygur, A. G., Şingirik, E., & Yücel, A. H (2019) Metotreksat kaynaklı hasarlarda alfa lipoik asit’in koruyucu etkisi. Arşiv Kaynak Tarama Dergisi, 28(3), 227-236
27. Yürük, A., & Ayaz, A (2014) The health effects of alpha lipoic acid. Hacettepe Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 1(1), 11-23
28. Ziegler, D., Hanefeld, M., Ruhnau, K. J., Hasche, H., Lobisch, M., Schutte, K., Malessa, R (1999) Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (Aladın III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care, 22(8), 1296-1301