The protective effect of coenzyme Q10 against methotrexate-induced hepatorenal toxicity in albino mice

Paper Details

Research Paper 01/05/2022
Views (561) Download (72)
current_issue_feature_image
publication_file

The protective effect of coenzyme Q10 against methotrexate-induced hepatorenal toxicity in albino mice

Ayah H. ALhawiti, Riham A. ALBalawi, Fatemah A. Zaid, Samirah M. Alessa, Romana M. ALGhorayed, Saja A. Albalawi, Amjad Ali Khan, Munerah Al Dawsari, Mervat S. Mohamed
Int. J. Biosci.20( 5), 120-129, May 2022.
Certificate: IJB 2022 [Generate Certificate]

Abstract

Methotrexate (MTX) is used to treat various clinical conditions, including autoimmune diseases like rheumatoid arthritis (RA), inflammatory diseases, and various cancers. However, clinical use has been restricted due to several adverse effects and toxicities. Coenzyme Q10 (CoQ10) is a safe and effective therapeutic antioxidant by being a free radical scavenger that blocks oxidative damage. CoQ10 also has anti-inflammatory effects. The study’s aim is to investigate if coenzyme Q10 (CoQ10) affects MTX-induced hepatotoxicity and nephrotoxicity. Forty albino mice were divided equally into four groups. The first group was referred to as “the control group,” and they were given a normal saline solution. The second group was dubbed the “Methotrexate group,” and they were given IP injections (10 mg/kg/day) on the fifth, sixth, and seventh days of the experiment. The third group was the CoQ10 group, which received orally administered CoQ10 (10 mg/kg/day) for seven consecutive days. The fourth group, which is the MTX+CoQ10 group, was pretreated with CoQ10 orally at a dose of 10 mg/kg/day for seven consecutive days and then received IP injections of MTX (10 mg/kg/day) for the last three days of the experiment. In mice injected with methotrexate, pretreatment with CoQ10 at a level of 10 mg/kg/day resulted in a drop in “liver function tests and renal function tests, as well as improvement in the liver and renal tissue,” according to the study. “Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver biomarkers, creatinine, urea, and BUN as kidney biomarkers,” as well as “histological appearance,” all improved. Coenzyme Q10 (CoQ10) protects the liver and kidneys from methotrexate-induced damage.

VIEWS 130

Abdel-Daim MM, Khalifa HA, Abushouk AI, Dkhil MA, Al-Quraishy SA. 2017. Diosmin attenuates methotrexate-induced hepatic, renal, and cardiac injury: A biochemical and histopathological study in mice. Oxidative Medicine and Cellular Longevity, 1–10. https://doi.org/10.1155/2017/3281670

Alcázar-Fabra M, Navas P, Brea-Calvo G. (2016). Coenzyme Q biosynthesis and its role in the respiratory chain structure. Biochimica Et Biophysica Acta (BBA) – Bioenergetics 1857(8), 1073–1078. https://doi.org/10.1016/j.bbabio.2016.03.010

Ali N, Rashid S, Nafees S, Hasan SK, Sultana, S. 2013. Beneficial effects of chrysin against methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis. Molecular and Cellular Biochemistry 385(1-2), 215–223. https://doi.org/10.1007/s11010-013-1830-4

Ali N, Rashid S, Nafees S, Hasan SK, 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. https://doi.org/10.1016/j.cbi.2017.05.002

ArenasJal M, SuñéNegre JM, GarcíaMontoya E. 2020. Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges. Comprehensive Reviews in Food Science and Food Safety 19(2), 574–594. https://doi.org/10.1111/1541-4337.12539

Bhagavan HN, Chopra RK. 2006. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radical Research 40(5), 445–453. https://doi.org/10.1080/10715760600617843

Caballero B, Allen L, Prentice A. 2005. Encyclopedia of human nutrition. Elsevier.

Carrascosa JM, de la Cueva P, Ara M, Puig L, Bordas X, Carretero G, Ferrándiz L., Sánchez-Carazo JL, Daudén E, López-Estebaranz JL, Vidal D, Herranz P, Jorquera E, Coto-Segura, P, Ribera M. 2016. Methotrexate in moderate to severe psoriasis: Review of the literature and expert recommendations. Actas Dermo-Sifiliográficas (English Edition) 107(3), 194–206. https://doi.org/10.1016/j.adengl.2016.01.025

Cecchino GN, Araujo Júnior E, Elito Júnior J. 2014. Methotrexate for ectopic pregnancy: When and how. Archives of Gynecology and Obstetrics 290(3), 417–423. https://doi.org/10.1007/s00404-014-3266-9

Crane FL. 2001. Biochemical functions of coenzyme Q10. Journal of the American College of Nutrition, 20(6), 591–598. https://doi.org/10.1080/07315724.2001.10719063

Dalaklioglu S, Genc GE, Aksoy NH, Akcit F, Gumuslu S. 2013. Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Human & Experimental Toxicology 32(6), 662–671. https://doi.org/10.1177/0960327112468178

Elsawy H, Alzahrani AM, Alfwuaires M, Abdel-Moneim AM, Khalil M. 2021. Nephroprotective effect of naringin in methotrexate induced renal toxicity in male rats. Biomedicine Pharmacotherapy 143, 112180. https://doi.org/10.1016/j.biopha.2021.112180

Farid Elbakry HR, Abdel Rahman Abdel Salam H, Saeid Abdelgayed S, Mohamed DA. 2022. Hepatorenal protective effects of sesame seeds oil, flaxseed oil and their mixture against methotrexate toxicity in rats. Iranian Journal of Toxicology 16(1), 51–62. https://doi.org/10.32598/ijt.16.1.877.1

Gossec L, Baraliakos X, McInnes I, Kerschbaumer A, de Wit M, Dougados M, Primdahl J, Van der Heijde D,  Smolen, J. S. 2020. Response to: ‘comment on: ‘EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update’ by gossec et al’ by wei et al. Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2020-218456

Hirano M, Garone C, Quinzii CM. 2012. Coq10 deficiencies and MNGIE: Two treatable mitochondrial disorders. Biochimica Et Biophysica Acta (BBA) – General Subjects 1820(5), 625–631. https://doi.org/10.1016/j.bbagen.2012.01.006

Jakubovic BD, Donovan A, Webster PM, &amp Shear NH. 2013. Methotrexate-induced pulmonary toxicity. Canadian Respiratory Journal, 20(3), 153–155. https://doi.org/10.1155/2013/527912

Kandemir FM, Kucukler S, Caglayan C, Gur C, Batil AA, Gülçin İ. 2017. Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties. Journal of Food Biochemistry 41(5). https://doi.org/10.1111/jfbc.12398

Kapoor P, Kapoor A. 2013. Coenzyme Q10–a novel molecule. Journal, Indian Academy of Clinical Medicine 14(1), 37-45.

Kim HN, Jeon DG, Lim Y, Jang IS. 2019. The effects of coenzyme Q10 supplement on blood lipid indices and hepatic antioxidant defense system in SD rats fed a high cholesterol diet. Laboratory Animal Research 35(1). https://doi.org/10.1186/s42826-019-0013-1

Kiremitli T, Kiremitli S, Akselim B, Yilmaz B, Mammadov R, Tor IH, Yazici GN, Amp Gulaboglu M. 2021. Protective effect of coenzyme Q10 on oxidative ovarian and uterine damage induced by methotrexate in rats. Human & Experimental Toxicology 40(9), 1537–1544. https://doi.org/10.1177/09603271211002891

Lee SQ, Tan TS, Kawamukai M, Chen ES. 2017. Cellular factories for coenzyme Q10 production. Microbial Cell Factories 16(1). https://doi.org/10.1186/s12934-017-0646-4

Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, Kardeh B, Parsa Y, Salimi Tabatabaee SA, Yadollah-Damavandi S, Parsa, T, Shahverdi E, Jangholi E. 2016. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxidative Medicine and Cellular Longevity 1–8. https://doi.org/10.1155/2016/5818479

Neves C, Jorge R, Barcelos A. 2009. The network of methotrexate toxicity. Acta reumatologica portuguesa. Retrieved April 28, 2022, from https://www.ncbi.nlm.nih.gov/pubmed/19449473

Ognjanović BI, Marković SD, Pavlović SZ, Žikić RV, Štajn AŠ, Saičić ZS. 2006. Combined effects of coenzyme Q10 and vitamin E in cadmium induced alterations of antioxidant defense system in the rat heart. Environmental Toxicology and Pharmacology 22(2), 219–224. https://doi.org/10.1016/j.etap.2006.03.008

Pannu AK. 2019. Methotrexate overdose in clinical practice. Current Drug Metabolism 20(9), 714–719. https://doi.org/10.2174/1389200220666190806140844.

Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, amp Döring F. 2008. Functions of coenzyme Q10in inflammation and gene expression. BioFactors 32(1-4), 179–183. https://doi.org/10.1002/biof.5520320121

Şener G, Ekşioğlu-Demiralp E, Çetiner M, Ercan F, amp Yeğen BÇ. 2006. Β-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. European Journal of Pharmacology 542(1-3), 170–178. https://doi.org/10.1016/j.ejphar.2006.02.056

Shan L, Ding Y, Fu Y, Zhou L, Dong X, Chen S, Wu H, Nai W, Zheng H, Xu W, Bai X, Jia C, Dai M. 2016. MTOR overactivation in mesenchymal cells aggravates CCL4− induced liver fibrosis. Scientific Reports 6(1). https://doi.org/10.1038/srep36037

Tawfik MK. 2015. Combination of coenzyme Q10 with methotrexate suppresses Freund’s complete adjuvant-induced synovial inflammation with reduced hepatotoxicity in rats: Effect on oxidative stress and inflammation. International Immunopharmacology 24(1), 80–87. https://doi.org/10.1016/j.intimp.2014.11.018

Visser K, Vander Heijde D, Dougados M. 2009. Methotrexate in rheumatoid arthritis: Experience and recommendations from the 3E initiative. International Journal of Clinical Rheumatology 4(3), 239–243. https://doi.org/10.2217/ijr.09.13

Weidmann A, Foulkes AC, Kirkham N, Amp Reynolds NJ. 2014. Methotrexate toxicity during treatment of chronic plaque psoriasis: A case report and review of the literature. Dermatology and Therapy 4(2), 145–156. https://doi.org/10.1007/s13555-014-0056-z

Xia S, Xu S, Amp Zhang X. 2006. Optimization in the preparation of coenzyme Q10 nanoliposomes.  Journal of Agricultural and Food Chemistry 54(17), 6358–6366. https://doi.org/10.1021/jf060405o