Metotreksat Kaynaklı Hasarlarda Alfa Lipoik Asit’in Koruyucu Etkisi

Yıl 2019, Cilt: 28 Sayı: 3, 227 - 236, 30.09.2019

Ayse Gul Uygur Ergin Şingirik , Ahmet Hilmi Yücel

Öz

1950’li yıllarda Metotreksat (MTX), antifolat
terapinin temeli olarak birçok kanser türünün tedavisinde aminopterinin yerini
almıştır. MTX, folik asit antagonistidir ve yüksek dozlarda timidilat sentetazı
inhibe ederek DNA oluşumunu engelleyen bir antineoplastik ilaçtır. Temelde
antimetabolit özelliğinden başka antiinflamatuvar, antiproliferatif,
immünosupresif, antipsöriatik etkinlikleri de bulunmakta ve klinikte halen bu
endikasyonlarda kullanılmaktadır. Ancak ilaç kullanımını takiben başta
hepatotoksisite ve nefrotoksisite olmak üzere meydana gelen yan etkiler, ilacın
kullanımını sınırlandırmaya veya ilacın kesilmesine neden olmaktadır. Yapılan çalışmalar, ilacın başta
hepatotoksisite olmak üzere gelişen yan etkilerinde, çoğunlukla reaktif oksijen
radikallerinin meydana getirdiği oksidatif hasarı sorumlu tutmuştur. Oksidatif
hasarın sorumlu olduğu gösterilen bu yan etkileri önleme konusunda, potent bir
antioksidan olan Alfa lipoik asitin alternatif bir profilaktik seçenek olabileceğini
düşünmekteyiz. Çalışmamızın amacı, MTX kaynaklı hasarlarda alfa lipoik asitin
koruyucu etkisini araştıran çalışmaları derleyerek yararını vurgulamaktır. Bu
amaçla 2008-2018 yıllarında, PubMed, Google ve Web of Science veri tabanlarında
metotreksat kaynaklı hasarlarda alfa lipoik asitin koruyucu etkisini araştıran
çalışmalar derlenmiştir. Alfa lipoik asit, lipoik asit ve metotreksat anahtar
sözcükleri kullanılarak tarama yapılmıştır.

Anahtar Kelimeler

Alfa lipoik asit, lipoik asit, metotreksat.

Protective Effect of Alpha Lipoic Acid on Methotrexate Damage

Öz

1950
Methotrexate (MTX) contains aminopterin as a carcinogen, based on antifolate
therapy. MTX is a folic acid antagonist and an antineoplastic drug that
inhibits DNA formation by inhibiting thymidylate synthetase at high doses.
Basically, antimetabolite is a special antiinflammatory, antiproliferative,
immunosuppressive, antipsychotic and clinically available indication.
Unfortunately, with hepatotoxicity and nephrotoxicity, depending on the side
effects, the drug is limited or the drug is discontinued. Studies have shown
that oxidative damage caused by reactive oxygen radicals is responsible for the
side effects of the drug as well as hepatotoxicity. This is a preferred
solution that has emerged as a problem. The aim of the work is to compile protection
against the disease. The aim of this paper was to emphasize
the benefit of compiling studies investigating the protective effect of alfalipoic
acid on MTX-induced damages. So, PubMed, Google or Web of Science were scanned
to document the research of the protective effect of alfalipoic acid on
MTX-induced damages from 2008 to 2018. Key words including Alfa lipoic acid, lipoic acid and methotrexate
were
searched.

Anahtar Kelimeler

Alfa lipoic acid, lipoic acid, methotrexate.

Kaynakça

• Martin SA, McCarthy A, Barber LJ, Burgess DJ, Parry S, Lord CJ, Ashworth A. Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol Med. 2009; 1(6-7): 323-37.
• Fiehn C. Methotrexate in rheumatology. Z Rheumatol. 2009; 68(9):747-56.
• Sathasivam S. Steroids and immunosuppressant drugs in myasthenia gravis. Nat Clin Pract Neurol. 2008; 4(6):317-27.
• Salim A, Tan E, Ilchyshyn A, Berth-Jones J. Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2006; 154: 1169-74.
• Jahovic N, Cevik H, Sehirli Ao, Yeğen BC, Sener G. Melatonin prevents Methotrexate-induced hepatorenal oxidative injury in rats. J Pineal Res. 2003; 34(4): 282-7.
• Kolli VK, Abraham P, Isaac B, Selvakumar D. Neutrophil infiltration and oxidative stress may play a critical role in methotrexate-induced renal damage. Chemotherapy. 2009; 55(2): 83-90.
• Cornelli U. Antioxidant use in nutraceuticals. Clin Dermatol. 2009; 27: 175–94.
• Yılmaz İ. Antioksidan içeren bazı gıdalar ve oksidatif stres. İnönü Üniversitesi Tıp Fakültesi Dergisi. 2010; 17(2): 143-53.
• Giacco R, Clemente G, Cipriano D, et al. Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people. Nutr Metab Cardiovasc Dis. 2010; 20(3): 186–94.
• Dündar Y, Aslan R. Hekimlikte oksidatif stres ve antioksidanlar. Afyon Kocatepe Üniversitesi Yayınları, Ankara, 2000.
• Cemeli E, Baumgartner A, Anderson D. Antioxidants and the comet assay. Mutat Res. 2009; 681: 51–67.
• Hassimotto NMA, Pinto MDS, Lajolo FM. Antioxidant status in humans after consumption of blackberry (Rubus fruticosus L.) juices with and without defatted milk. J Agric Food Chem. 2008; 56: 11727–33.
• Moure A, Cruz JM, Franco JD, et al. Natural antioxidants from residual sources. Food Chem. 2001; 172: 145–71.
• Ratnam DV, Ankola DD, Bhardwaj V, et al. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J Control Release 2006; 113: 189–207.
• Yavaşer R. Doğal ve Sentetik Antioksidan Bileşiklerin Antioksidan Kapasitelerinin Karşılaştırılması. Yüksek Lisans Tezi, Adnan Menderes Üniversitesi, Aydın, 2011.
• Karabulut H, Gülay ŞH. Antioksidanlar. Mehmet Akif Ersoy Veteriner Fakültesi Dergisi. 2016; 1(1): 65-76.
• Çavdar C, Sifil A, Çamsarı T. Reaktif oksijen partikülleri ve antioksidan savunma. Türk Nefroloji Diyaliz ve Transplantasyon Dergisi. 1997; 3(4): 92-5.
• Tetikçok R, Özçetin M, Çeltek NY, Oktay G, Ünlü U, Şengül M. Lipoik Asit. 2015; 5(3): 206-9.
• Yapar SB, Eskiocak S. Alfa lipoik asidin rat karaciğer homojenatlarında hidrojen peroksit ile indüklenmiş lipid peroksidasyonuna etkisi. Türk Biyokimya Dergisi. 2014; 39(3): 317-27.
• Karaca EG. Lipoik Asit Evrensel Antioksidan. Afyon Kocatepe Fen Bilimleri Dergisi. 2008; 8(1): 231-46.
• Gutteridge J.M. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin. Chem.1995; 41(12): 1819-28.
• Kagan VE, Shvedova A, Serbinova E. Dihidrolipoic acid-a universal antioxidant both in the membrane and in the aqueous phase. Reductıon of peroxyl ascorbyl and chromanoxyl radicals. Biochem pharmacol.1992; 44: 1637-49.
• Packer L, Witt E, Tritschler HJ. Alfa lipoic acid as a biological antioxidant. Science Direct Free Radical Biology Medicine. 1995; 19(2): 227-50.
• Ou P, Tritschler HJ, Wolff SP. Lipoik acid: a therapeutic metal chelating antioksidant? Biochem Pharmacol. 1995; 50(1): 123-6.
• Jacop S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. Improvement of insülin stimulated glucose disposal in type 2 diabetes after repeated parenteral administiration of thioctic acid. Exp Clin Endocrinol Diabetes. 1996; 104: 284-8.
• Biewenga G, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmac.1997; 29: 315-331.
• Snell EE, Strong FM, Peterson WH. Growth factors for bacteria. Biochem J. 1937; 31: 1789-99.
• Şentürk N. Metotreksat. Arch Turk Dermatol Venerology. 2016; 50(1): 18-21.
• Savran M. Ratlarda Metoreksat Kaynaklı Karaciğer ve Böbrek Hasarında C Vitamininin Koruyucu Etkisinin Araştırılması. Tıpta Uzmanlık Tezi, Süleyman Demirel Üniversitesi, Isparta, 2011.
• Aşcı H. Metoreksat Kaynaklı Karaciğer ve Böbrek Hasarında Misoprostolün Koruyucu Etkisi. Tıpta Uzmanlık Tezi, Süleyman Demirel Üniversitesi, Isparta, 2010.
• Vardı N, Parlakpınar H, Çetin A, Erdoğan A, Öztürk IÇ. Protective Effect of Beta Carotene on Methotrexate Induced Oxidative Liver Damage. Toxicologic Pathology. 2010; 38: 592-7.
• Akbulut S, Elbe H, Eris C, Doğan Z, Toprak G, Otan E, Erdemli E, Turkoz Y. Cytoprotective effect of amifostine ascorbic acid and n- acetylcysteine against methotrexate ınduced hepatotoxicity in rats. World Journal of Gastrpenterology. 2014; 20(29): 10158-65.
• Kose E, Sapmaz HI, Sarihan E, Vardi N, Turkoz Y, Ekinci N. Beneficial effects of montelukast against methotrexateinducedliver toxicity: a biochemical and histological study. ScientificWorldJournal. 2012.
• Soliman ME. Evaluation of the possible protective role of folic acid on the liver toxicity ınduced experimentally by methotrexate in adult male albino rats. Egypt J Histol. 2009; 32: 118-128.
• Cetin A, Kaynar L, Eser B, Karada C, Saraymen B, Öztürk A. Beneficial effects of propolis on methotrexate-induced liver injury in rats. Acta Oncologica Turcica. 2011; 44: 18-23.
• Cetinkaya A, Bulbuloglu E, Kurutas EB, Kantarceken B. N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats. Med Sci Monit. 2006.
• Kahraman H, Kurutas E, Tokur M, Bozkurt S, Cıralık H, Kabakcı B. Protective effectsof erythropoietin and n-acetylcysteine on methotrexate-induced lung injury in rats. Balkan Med J. 2013; 30: 99-104.
• Armağan İ. Metotreksat’ın karaciğerde be böbrekte neden olduğu hasarda oksidatif stresin rolü. Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi. 2015; 22(4): 152-5.
• Goodman, Gillman. Tedavinin Farmakolojik Temeli. İstanbul, Nobel Tıp Kitabevleri, 2009: 1315-405.
• Arpag H, Gül M, Aydemir Y, Atilla N,Yiğitcan B, Cakir T, Polat C, Şehirli Ö, Sayan M. Protective effects of alpha-lipoic acid on methotrexate-ınduced oxidative lung ınjury in rats. Journal of Investigative Surgery. 2018; 31: 107-13.
• Ahmed AAM, Selim MAA, Elsayad NM. Alfa-Lipoic acid ameliorates oral mucositis and oxidative stress induced by methotrexate in rats. Histological and immunohistochemical study. Life Sciences. 2017; 171: 51-9.
• Karapınar OS, Pınar N, Özcan O, Özgür T, Dolapçıoğlu K. Protective effect of alpha lipoic acid in methotrexate induced ovarian oxidative injury and decreased ovarian reserve in rats. Gynecol Endocrinol. 2017; 33(8): 653-9.
• Armağan I, Bayram D, Candan IA, Yiğit A, Çelik E, Armağan HH, Uğuz AC. Effects of pentoxifylline and alpha lipoic acid onmethotrexate-induced damage in liver and kidney of rats. Environmental Toxicology And Pharmacology. 2015; 39: 1122-31.
• Çakır T, Baştürk A, Polat C, Aslaner A, Durgut H, Şehirli AÖ, M Gül, Öğünç AV, Gül S, Sabuncuoglu MZ, Oruç MT. Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats? 2015; 30(4): 247-54.
• Çakır T, Polat C, Baştürk A, Gül M, Aslaner A, Durgut H, Şehırlı AÖ, Aykaç A, Bahar L, Sabuncuoglu MZ. The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. European Review for Medical and Pharmacological Sciences. 2015; 19: 2132-9.
• Guais A, Baronzio GF, Sanders E, Campion F, Mainini C, Fiorentini G, Montagnani F, Behzadi M, Schwartz L, Abolhassani M. Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report. Invest New Drugs. 2012; 30: 200-11.
• Somi MH, Hajipour B, Abad GDA, Hemmati MR, Ghabili K, Khodadadi A, Vatankhah AM. Protective role of lipoic acid on methotrexate induced intestinal damage in rabbit model. 2011; 30(1): 38-40.
• Dadhania VP, Tripathi DN, Vikram A, Ramarao P, Jena GB. Intervention of lipoic acid ameliorates methotrexate-induced oxidative stress and genotoxicity: A study in rat intestine. Chemico Biological Interactions. 2010; 183: 85-97.
• Tabassum H, Parvez S, Pasha ST, Banerjee BD, Raisuddin S. Protective effect of lipoic acid against methotrexate induced oxidative stress in liver mitochondria. Food and Chemical Toxicology: An International Journal Published For The British Industrial Biological Research Association. 2010;48(7):1973-9.
• Thibodeau PA, Bedard SK, Courteau J, Niyonsenga T, Paquette B. Thiols can either enhance or suppress dna damage induction by catecholestrogens. Free Radical Biology Medicine. 2001; 30(1): 62-73.