ارزیابی اثر حفاظتی داروی پروپوفول بر اختلالات بافت کبد ناشی از تجویز متوترکسات در موش صحرایی نر نژاد ویستار

نویسندگان

  • سارا پورمحمدی دزفولیان - دانشجوی پزشکی عمومی، دانشکده پزشکی، دانشگاه علوم پزشکی دزفول، دزفول، ایران.
  • سوسن صباغ - گروه آناتومی، دانشکده پزشکی، دانشگاه علوم پزشکی دزفول، دزفول، ایران.
  • مرتضی حبیبی مقدم - دانشکده پیراپزشکی، دانشگاه علوم پزشکی دزفول، دزفول، ایران.
  • زهرا اسلامی فر - دانشکده پیراپزشکی، دانشگاه علوم پزشکی دزفول، دزفول، ایران.

DOI::

https://doi.org/10.22100/jkh.v17i3.2883

چکیده

مقدمه: متوترکسات (Methotrexate: MTX) یک داروی سیتوتوکسیک است که در برابر برخی بیماری‌ها و تومورها تجویز می‌شود که کاربرد آن به‌دلیل برخی عوارض جانبی محدود شده است. پروپوفول یک داروی با خاصیت آنتی‌اکسیدانی یکی از داروهای آرام‌بخشی و بیهوشی مطلوب می‌باشد. هدف این مطالعه ارزیابی اثر پروپوفول در برابر سمیت کبدی ناشی از متوترکسات می‌باشد.

مواد و روش‌ها: تعداد 24 رت به 4 گروه تقسیم شدند: گروه کنترل (گاواژ آب مقطر) گروه پروپوفول (10 mg/kg سه بار در هفته) گروه متوترکسات (20 mg/kg در روزهای17 و 18) و گروه پروپوفول-متوترکسات. تزریقات درون صفاقی و مدت مطالعه 21 روز بود. سپس تمام موش‌ها بیهوش شدند و پلاسما برای تخمین آسپارتات آمینوترانسفراز (Aspartate aminotransferase: AST)، آلانین آمینوترانسفراز (Alanine aminotransferase: ALT) و لاکتات دهیدروژناز (Lactate dehydrogenase: LDH) و همچنین بیلیروبین توتال جمع‌آوری شد. بافت کبد جهت مطالعه شاخص‌های هیستوپاتولوژیک جداسازی شد.

نتایج: در مقایسه گروه MTX با گروه pro-MTX مشاهده شد پروپوفول به‌طور معنی‌داری موجب کاهش سطح آنزیم‌های AST و ALT شد (0001/0P<) اما اثر آن بر کاهش ALP و LDH معنی‌دار نبود. تغییرات بیلیروبین توتال بر هیچ گروهی معنی‌دار نبود. در بررسی تغییرات هیستوپاتولوژیک کبدی، در گروه MTX، نکروز سلولی، دژنراسیون سلولی، ارتشاح لکوسیت‌ها، پرخونی ورید مرکزی و اتساع سینوزوئیدها دیده شد. آسیب در گروه pro-MTX در برابر گروه MTX به شکل معنی‌داری کاهش یافت (0001/0P<).

نتیجه‌گیری: نتایج تحقیق حاضر نشان داد که پروپوفول در برابر سمیت کبدی ناشی از متوترکسات اثرات محافظتی دارد، اما برای کاربرد بالینی، مطالعات بیشتری موردنیاز است.

مراجع

Herfarth HH. Methotrexate for inflammatory bowel diseases-new developments. Digestive Diseases 2016;34:140-6. doi: 10.1080/14740338.2017.1310839

Howard SC, McCormick J, Pui C-H, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. The Oncologist 2016;21:1471. doi: 10.1634/theoncologist.2015-0164

Khafaga AF, El-Sayed YS. Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation. Life Sciences 2018;196:9-17. doi: 10.1016/j.lfs.2018.01.010

Pountos I, Giannoudis PV. Effect of methotrexate on bone and wound healing. Expert Opinion on Drug Safety 2017;16:535-45. doi: 10.1080/14740338.2017.1310839

Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard J-P. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. The Journal of Clinical Investigation 1998;102:322-8.

Kobayashi K, Terada C, Tsukamoto I. Methotrexate-induced apoptosis in hepatocytes after partial hepatectomy. European Journal of Pharmacology 2002;438:19-24. doi: 10.1016/S0014-2999(02)01264-5

Spurlock III CF, Tossberg JT, Fuchs HA, Olsen NJ, Aune TM. Methotrexate increases expression of cell cycle checkpoint genes via JNK activation. Arthritis & Rheumatism 2012;64:1780-9. doi: 10.1002/art.34342

Hoshyar R, Sebzari A, Balforoush M, Valavi M, Hosseini M. The impact of Crocus sativus stigma against methotrexate-induced liver toxicity in rats. Journal of Complementary and Integrative Medicine 2020;17. doi: 10.1515/jcim-2019-0201

Fayez AM, Zakaria S, Moustafa D. Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats. Biomedicine & Pharmacotherapy 2018;105:428-33. doi: 10.1016/j.biopha.2018.05.145

Kalantar M, Kalantari H, Goudarzi M, Khorsandi L, Bakhit S, Kalantar H. Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacological Reports 2019;71:746-52. doi: 10.1016/j.pharep.2019.04.004

Dröge W. Free radicals in the physiological control of cell function. Physiological Reviews;2002. doi: 10.1152/physrev.00018.2001

Eleveld D, Colin P, Absalom A, Struys M. Pharmacokinetic–pharmacodynamic model for propofol for broad application in anaesthesia and sedation. British Journal of Anaesthesia 2018;120:942-59. doi: 10.1016/j.bja.2018.01.018

Cillo Jr JE, Finn R. Hemodynamics in elderly coronary artery disease patients undergoing propofol sedation. Journal of Oral and Maxillofacial Surgery 2006;64:1338-42. doi: 10.1016/j.joms.2006.05.018

Brohan J, Goudra BG. The role of GABA receptor agonists in anesthesia and sedation. CNS Drugs 2017;31:845-56. doi: 10.1007/s40263-017-0463-7

Joo HS, Perks WJ. Sevoflurane versus propofol for anesthetic induction: a meta-analysis. Anesthesia & Analgesia. 2000;91:213-9. doi: 10.1213/00000539-200007000-00040

Sahinovic MM, Struys MM, Absalom AR. Clinical pharmacokinetics and pharmacodynamics of propofol. Clinical Pharmacokinetics 2018;57:1539-58. doi: 10.1007/s40262-018-0672-3

Wheeler DS, Vaux KK, Ponaman ML, Poss BW. The safe and effective use of propofol sedation in children undergoing diagnostic and therapeutic procedures: experience in a pediatric ICU and a review of the literature. Pediatric Emergency Care 2003;19:385-92. doi: 10.1097/01.pec.0000101578.65509.71

Chang Y-F, Chao A, Shih P-Y, Hsu Y-C, Lee C-T, Tien Y-W, et al. Comparison of dexmedetomidine versus propofol on hemodynamics in surgical critically ill patients. Journal of Surgical Research 2018;228:194-200. doi: 10.1016/j.jss.2018.03.040

Marik PE. Propofol: therapeutic indications and side-effects. Current Pharmaceutical Design 2004;10:3639-49. doi: 10.2174/1381612043382846

GÜLÇin I, Alici HA, Cesur M. Determination of in vitro antioxidant and radical scavenging activities of propofol. Chemical and Pharmaceutical Bulletin 2005;53:281-5. doi: 10.1248/cpb.53.281

Han C, Ding W, Jiang W, Chen Y, Hang D, Gu D, et al. A comparison of the effects of midazolam, propofol and dexmedetomidine on the antioxidant system: a randomized trial. Experimental and Therapeutic Medicine 2015;9:2293-8. doi: 10.3892/etm.2015.2410

Santhakumar P, Roy A, Ganesh MK, Selvaraj J, Prathap L, Babu KY. Ethanolic extract of Capparis decidua fruit ameliorates methotrexate-induced hepatotoxicity by suppressing oxidative stress and inflammation by modulating nuclear factor-kappa B signaling pathway. Pharmacognosy Magazine 2021;17:143. doi: 10.4103/pm.pm_402_20

Elsawy H, Algefare AI, Alfwuaires M, Khalil M, Elmenshawy OM, Sedky A, et al. Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells. Bioscience Reports 2020;40:BSR20193686. doi: 10.1042/BSR20193686

Khatab LA, Abdel-Raheem IT, Ghoneim AI. Protective effects of melatonin and l-carnitine against methotrexate-induced toxicity in isolated rat hepatocytes. Naunyn-Schmiedeberg's Archives of Pharmacology 2022;395:87-97. doi: 10.1007/s00210-021-02176-1

Hafez SMNA, Elbassuoni E, Abdelzaher WY, Welson NN, Batiha GE-S, Alzahrani KJ, et al. Efficacy of vitamin E in protection against methotrexate induced placental injury in albino rats. Biomedicine & Pharmacotherapy 2021;139:111637. doi: 10.1016/j.biopha.2021.111637

Mohammed DS, Al-Gareeb AIA. Effects of omega-3 and vitamin c on methotrexate-induced liver injury. Mustansiriya Medical Journal 2021;20:39. doi: 10.4103/MJ.MJ_6_21

Jahovic N, Çevik H, Şehirli AÖ, Yeğen BÇ, Şener G. Melatonin prevents methotrexate‐induced hepatorenal oxidative injury in rats. Journal of Pineal Research 2003;34:282-7. doi: 10.1034/j.1600-079X.2003.00043.x

Al-Motabagani MA. Histological and histochemical studies on the effects of methotrexate on the liver of adult male albino rat. Int J Morphol 2006;24:417-22.

Tunalı-Akbay T, Sehirli O, Ercan F, Sener G. Resveratrol protects against methotrexate-induced hepatic injury in rats. Journal of Pharmacy & Pharmaceutical Sciences 2010;13:303-10. doi: 10.18433/J30K5Q

Rosen H, Keeffe E. Evaluation of abnormal liver enzymes, use of liver test, and the serology of viral hepatitis. Liver disease diagnosis and management. 2000:24-35.

Chen Y, Li Z. Protective Effects of Propofol on Rats with Cerebral Ischemia–Reperfusion Injury Via the PI3K/Akt Pathway. Journal of Molecular Neuroscience 2021;71:810-20. doi: 10.1007/s12031-020-01703-8

Hausburg MA, Banton KL, Roman PE, Salgado F, Baek P, Waxman MJ, et al. Effects of propofol on ischemia-reperfusion and traumatic brain injury. Journal of Critical Care 2020;56:281-7. doi: 10.1016/j.jcrc.2019.12.021

Ma H, Liu Y, Li Z, Yu L, Gao Y, Ye X, et al. Propofol Protects Against Hepatic Ischemia Reperfusion Injury via Inhibiting Bnip3-Mediated Oxidative Stress. Inflammation 2021;1-14. doi: 10.1007/s10753-021-01416-z

Peng X, Li C, Yu W, Liu S, Cong Y, Fan G, et al. Propofol attenuates hypoxia-induced inflammation in BV2 microglia by inhibiting oxidative stress and NF-κB/Hif-1α signaling. BioMed Research International 2020;2020. doi: 10.1155/2020/8978704

Yao Y, Zhang JJ. Propofol induces oxidative stress and apoptosis in vitro via regulating miR‐363‐3p/CREB signalling axis. Cell Biochemistry and Function 2020;38:1119-28. doi: 10.1002/cbf.3572

Ansley DM, Lee J-u, Godin DV, Garnett ME, Qayumi AK. Propofol enhances red cell antioxidant capacity in swine and humans. Canadian Journal of Anaesthesia 1998;45:233-9. doi: 10.1007/BF03012908

Tesauro M, Thompson W, Moss J. Effect of staurosporine-induced apoptosis on endothelial nitric oxide synthase in transfected COS-7 cells and primary endothelial cells. Cell Death & Differentiation 2006;13:597-606. doi: 10.1038/sj.cdd.4401770

McDermott BJ, McWilliams S, Smyth K, Kelso EJ, Spiers JP, Zhao Y, et al. Protection of cardiomyocyte function by propofol during simulated ischemia is associated with a direct action to reduce pro-oxidant activity. Journal of Molecular and Cellular Cardiology 2007;42:600-8. doi: https://doi.org/10.1016/j.yjmcc.2006.12.002

Xu J-J, Wang Y-L. Propofol attenuation of hydrogen peroxide-mediated oxidative stress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1. European Journal of Anaesthesiology 2008;25:395-402. doi: 10.1017/S0265021508003542

Sayin M, Özatamer O, Taşöz R, Kilinc K. Propofol attenuates myocardial lipid peroxidation during coronary artery bypass grafting surgery. British Journal of Anaesthesia 2002;89:242-6. doi: 10.1093/bja/aef173

Wills P, Asha V. Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats. Journal of Ethnopharmacology 2006;108:320-6. doi: 10.1016/j.jep.2006.05.032

Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. Journal of Hepatology 2019;70:151-71. doi: 10.1016/j.jhep.2018.09.014

Devarbhavi H, Choudhury AK, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al. Drug-induced acute-on-chronic liver failure in Asian patients. Official journal of the American College of Gastroenterology 2019;114:929-37. doi: 10.14309/ajg.0000000000000201

Ezhilarasan D, Raghunandhakumar S. Boldine treatment protects acetaminophen‐induced liver inflammation and acute hepatic necrosis in mice. Journal of Biochemical and Molecular Toxicology 2021;35:e22697. doi: 10.1002/jbt.22697

Pliquett RU, Lübbert C, Schäfer C, Girndt M. Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report. Journal of Medical Case Reports 2020;14:1-5. doi: 10.1186/s13256-020-2349-4

Devarbhavi H, Aithal G, Treeprasertsuk S, Takikawa H, Mao Y, Shasthry SM, et al. Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines. Hepatology International 2021;15:258-82. doi: 10.1007/s12072-021-10144-3

Ferreira I, Gouveia C, Vasques Sr C, Faria C, Pedroso A. Drug-Induced Liver Injury Caused by Amoxicillin/Clavulanate. Cureus 2020;12. doi: 10.7759/cureus.12234

Gelfand JM, Wan J, Zhang H, Shin DB, Ogdie A, Syed MN, et al. Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: A population-based study. Journal of the American Academy of Dermatology 2021;84:1636-43. doi: 10.1016/j.jaad.2021.02.019

Ezhilarasan D. Hepatotoxic potentials of methotrexate: Understanding the possible toxicological molecular mechanisms. Toxicology 2021;458:152840. doi: 10.1016/j.tox.2021.152840

Mahmoud AM, Hussein OE, Hozayen WG, Bin-Jumah M, Abd El-Twab SM. Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats. Environmental Science and Pollution Research 2020;27:7910-21. doi: 10.1007/s11356-019-07532-6

Roghani M, Kalantari H, Khodayar MJ, Khorsandi L, Kalantar M, Goudarzi M, et al. Alleviation of liver dysfunction, oxidative stress and inflammation underlies the protective effect of ferulic acid in methotrexate-induced hepatotoxicity. Drug Design, Development and Therapy 2020;14:1933. doi: 10.2147/DDDT.S237107

Soliman MM, Aldhahrani A, Alkhedaide A, Nassan MA, Althobaiti F, Mohamed WA. The ameliorative impacts of Moringa oleifera leaf extract against oxidative stress and methotrexate-induced hepato-renal dysfunction. Biomedicine & Pharmacotherapy 2020;128:110259. doi: 10.1016/j.biopha.2020.110259

Owumi S, Ajijola I, Agbeti O. Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate. Human & Experimental Toxicology 2019;38:1254-65. doi: 10.1177/0960327119871095

Santhakumar P, Roy A, Mohanraj KG, Jayaraman S, Durairaj R. Ethanolic Extract of Capparis decidua Fruit Ameliorates Methotrexate-Induced Hepatotoxicity by Activating Nrf2/HO-1 and PPAR gamma Mediated Pathways. Indian Journal of Pharmaceutical Education and Research 2021;55:S265-74. doi: 10.4103/pm.pm_402_20

Çakır T, Özkan E, Dulundu E, Topaloğlu Ü, Şehirli AÖ, Ercan F, et al. Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats. Journal of Pharmacy and Pharmacology 2011;63:1566-71. doi: 10.1155/2014/561971

Kobayashi K, Yoshino F, Takahashi S-S, Todoki K, Maehata Y, Komatsu T, et al. Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy. The Journal of the American Society of Anesthesiologists 2008;109:426-35. doi: 10.1097/ALN.0b013e318182a903

Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H, Goudarzi M. Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomedicine & Pharmacotherapy 2018;97:233-9. doi: 10.1016/j.biopha.2017.10.113

فایل‌های دیگر

چاپ شده

2022-09-28

شماره

نوع مقاله

مقاله پژوهشي