Histological changes in methotrexate hepatotoxicity after boron application and evaluation of serum thiol-disulfide balance

Yıl 2021, Cilt: 4 Sayı: 3, 277 - 282, 21.05.2021

Andaç Kipalev Neşelioğlu , Gülben Akcan , Hilal Nakkaş , Salim Neşelioğlu , Özcan Erel , Oya Evirgen , Meltem Özgüner

https://doi.org/10.32322/jhsm.895444

Öz

Aim: Methotrexate, a folic acid antagonist, is a chemotherapeutic drug used in the treatment of various inflammatory diseases as well as some cancer types.The purpose of this study; It is the study of the effects of boric acid against the hepatotoxic side effects of methotrexate.
Materials and Methods: Male wistar albino rats were divided into five groups of six animals each. The rats in group 1 were used as a control group. Methotrexate was administered to the rats in group 2 and boric acid to the rats in group 3. While the rats in group 4 were given first methotrexate and then boric acid, the rats in group 5 were administered boric acid first and then methotrexate.
Results: Light microscopic examination revealed sinusoidal dilatation, hepatocyte degeneration, vascular congestion-thrombosis, and inflammatory infiltration in the livers of rats treated with methotrexate. It was observed that the protective effect of boric acid was more effective than its treatment. In the groups given methotrexate, the level of oxidative stress-related parameters such as lipid hydroperoxide, MPO and disulfide increased (p< 0.05), whereas the level of antioxidant parameters such as native thiol, total thiol and catalase decreased (p< 0.05).
Conclusion: In this study, it was determined that the protective effect of boric acid was more than the therapeutic effect in liver damage caused by methotrexate. Oxidative hepatotoxicity resulting from methotrexate application disrupted the thiol disulfide balance and caused it to shift in favor of oxidation.

Anahtar Kelimeler

Boric acid, disulfide, Methotrexate, oxidative stres, thiol

Kaynakça

• Güven E, Erişgin Z, Tekelioğlu Y. Siçanlarda metotreksat kaynakli testis hasari üzerine shilajitin’in histopatolojik etkisi. Kocatepe Tıp Derg 2017; 18: 1-6.
• Uygur Ag, Şingirik E, Yücel AH. Metotreksat kaynaklı hasarlarda alfa lipoik asit’in koruyucu etkisi. Arşiv Kaynak Tarama Derg 2019; 28: 227-36.
• Ince S, Keles H, Erdogan M, Hazman O, Kucukkurt I. Protective effect of boric acid against carbon tetrachloride–induced hepatotoxicity in mice. Drug and chemical toxicology 2012; 35: 285-92.
• Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014; 47: 326-32.
• Jiang ZY, Woollard AC, Wolff SP. Lipid hydroperoxide measurement by oxidation of Fe2+ in the presence of xylenol orange. Comparison with the TBA assay and an iodometric method. Lipids 1991; 26: 853-6.
• Thike AA, Chng MJ, Tan PH, Fook-Chong S. Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H-score with pathological parameters. Pathology 2001; 33: 21-5.
• Góth L. A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta; Int J Clin Chem 1991; 196: 143-51.
• Tilling L, Townsend S, David J. Methotrexate and hepatic toxicity in rheumatoid arthritis and psoriatic arthritis. Clin Drug Invest 2006; 26: 55-62.
• Devrim E, Çetin R, Kılıçoğlu B, Imge Ergüder B, Avcı A, Durak İ. Methotrexate causes oxidative stress in rat kidney tissues. Renal Failure 2005; 27: 771-3.
• Elsawy H, Algefare AI, Alfwuaires M, et al. Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells. Bioscience Reports 2020; 40(6).
• Ulukaya S. Hepatobiliyer Hastalıklarda Anestezi. JCAM 389-99.
• Armagan I, Bayram D, Candan IA, et al. Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats. Environmental toxicology and pharmacology 2015; 39: 1122-31.
• Surai P. Carnitine Enigma: from antioxidant action to vitagene regulation part 2. transcription factors and practical applications. J Veter Sci Med 2015; 3: 17.
• Wang B, Chen M-S, Cao T, et al. editors. Method development for determining methotrexate in urine by micellar electrokinetic capillary chromatography. Medicine and Biopharmaceutical: Proceedings of the 2015 International Conference; 2016: World Scientific.
• Bordbar M, Shakibazad N, Fattahi M, Haghpanah S, Honar N. Effect of ursodeoxycholic acid and vitamin E in the prevention of liver injury from methotrexate in pediatric leukemia. The Turkish Journal of Gastroenterology 2018; 29: 203.
• Kılıc S, Emre S, Metin A, Isıkoglu S, Erel O. Effect of the systemic use of methotrexate on the oxidative stress and paraoxonase enzyme in psoriasis patients. Archives of dermatological research 2013; 305: 495-500.
• Babiak RM, Campello AP, Carnieri EG, Oliveira MB. Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct 1998; 16: 283-93.
• Uraz S, Tahan V, Aygun C, et al. Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity. Dig Dis Sci 2008; 53: 1071-7.
• Jahovic N, Çevik H, Şehirli AÖ, Yeğen BÇ, Şener G. Melatonin prevents methotrexate‐induced hepatorenal oxidative injury in rats. J Pineal Res 2003; 34: 282-7.
• Armağan İ. Metotreksat’ın karaciğer ve böbrekte neden olduğu hasarda oksidatif stresin rolü. SDÜ Tıp Fakültesi Derg 2015; 22.
• Mercan U. Toksikolojide serbest radikallerin önemi. Yüzüncü Yıl Üniversitesi Veteriner Fakültesi Derg 2004; 15: 91-6.
• Sogut I, Paltun SO, Tuncdemir M, Ersoz M, Hurdag C. The antioxidant and antiapoptotic effect of boric acid on hepatoxicity in chronic alcohol-fed rats. Canadian J Physiol Pharmacol 2018; 96: 404-11.
• Güneş E, Büyükgüzel E. Oxidative effects of boric acid on different developmental stages of Drosophila melanogaster Meigen, 1830 (Diptera: Drosophilidae). Türkiye Entomoloji Derg 2017; 41: 3-15.
• Cengiz M. Boric acid protects against cyclophosphamide-induced oxidative stress and renal damage in rats. Cell Molecul Biol 2018; 64: 11-4.
• Micoogullari U, Karatas OF, Kisa E, et al. Thiol/disulfide homeostasis in patients with erectile dysfunction. J Sex Med 2020; 17: 1934-41.
• Sezgin B, Kinci MF, Pirinççi F, et al. Thiol-disulfide status of patients with cervical cancer. J Obstet Gynaecol Res 2020; 46: 2423-9.
• Erel Ö, Neşelioğlu S, Ergin Tunçay M, et al. A sensitive indicator for the severity of COVID-19: thiol. Turk J Med Sci 2020.
• Efe A, Neşelioğlu S, Soykan A. An Investigation of the dynamic thiol/disulfide homeostasis, as a novel oxidative stress plasma biomarker, in children with autism spectrum disorders. Autism Res 2021; 14: 473-87.
• Elango T, Dayalan H, Gnanaraj P, Malligarjunan H, Subramanian S. Impact of methotrexate on oxidative stress and apoptosis markers in psoriatic patients. Clin Exp Med 2014; 14: 431-7.
• Moghadam AR, Tutunchi S, Namvaran-Abbas-Abad A, et al. Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress. BMC Complement Altern Med 2015; 15: 246.
• Akşit H, Akşit D, Bildik A, Hatibe K, Yavuz Ö, Seyrek K. Deneysel karaciğer intoksikasyonunda N-asetil sistein’in glutatyon metabolizması ve lipid peroksidasyonuna etkileri. Ankara Üniversitesi Veteriner Fakültesi Derg 2015; 62: 1-5.
• Gül M, Ayan M, Seydanoğlu A, et al. The effect of N-acetyl cysteine on serum glutathione, TNF-α and tissue malondialdehyde levels in the treatment of sepsis. Turk J Trauma Emerg Surg 2011; 17: 293-7.
• Ommati MM, Amjadinia A, Mousavi K, Azarpira N, Jamshidzadeh A, Heidari R. N-acetyl cysteine treatment mitigates biomarkers of oxidative stress in different tissues of bile duct ligated rats. Stress 2020: 1-16.