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Usunobun U, Inuumoru C S, Onyeaghor C, Lawuru D, Egbo H. Nephroprotective Potential of Chromolaena odorata (L.) R.M. King & H. Rob. on Methotrexate-Induced Kidney Damage and Oxidative Stress. Journal of Research in Applied and Basic Medical Sciences 2022; 8 (3) :118-127
URL: http://ijrabms.umsu.ac.ir/article-1-217-en.html
PhD Edo State University Uzairue, Department of Biochemistry, Iyamho, ‎Edo State‎, ‎Nigeria , usunobun.usunomena@edouniversity.edu.ng
Abstract:   (1051 Views)
Background & Aims: Methotrexate despite its beneficial anti-cancer and immunosuppressant effects has continued to receive limitation in usage due to its organ toxicity. The aim of this study was to investigate the nephroprotective effect of aqueous leaf extract of Chromolaena odorata on Methotrexate-induced injury and damage on kidney in rat.
Materials & Methods: The study consisted of four groups of rats: Control, Chromolaena odorata extract, Methotrexate, and Methotrexate+Chromolaena odorata extract groups. Chromolaena odorata extract was given orally (200 mg/kg) for 10 days, and Methotrexate at a single dose (20 mg/kg) was administered intraperitoneally on day 9 of the experiment. Blood and kidney were collected on day 11 to measure biochemical, hematological and oxidative stress parameters as well as histopathological analysis.
Results: Methotrexate administration when compared to control and extract, treated rats decreased antioxidant agents, including catalase (CAT) and Superoxide dismutase (SOD) while it increased the Malondialdehyde level in the kidney tissues. Methotrexate also increased Urea and Creatinine in the blood samples. The result also showed that Methotrexate administration produced a significant decrease in Hemoglobin (HB), White Blood Cell (WBC), Hematocrit (HCT), Red Blood Cell (RBC), Platelets (PLTS), Lymphocyte, Basophil, and Monocyte when compared to control and all extract administered rats. The result of histopathological analysis of the kidney revealed that Methotrexate administration caused necrosis of renal tubules, renal congestion, renal tubule epithelium swelling, interstitial hemorrhage, glomerular atrophy, as well as dilatation. Chromolaena odorata extract administration significantly alleviated kidney function, improved antioxidant parameters, decreased levels of oxidative stress agents, restored the hematological parameters towards normalcy as well as resulted in noticeable improvement and attenuation toward normalcy in the kidney structure, and thus, remarkably preventing Methotrexate-induced tissue injury and damage.
Conclusion: The observed data showed that Chromolaena odorata had a protective effect against Methotrexate-induced nephrotoxicity by maintaining the activity of the antioxidant defense system, which can be attributed to its bioactive constituents.
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1. Lalith G. Invasive Plants: A guide to the identification of the most invasive plants of Sri Lanka. Colombo 2009. P. 116-7.
2. King RM, Robinson H. Chromolaena odorata (Linnaeus). Phytolgia. Flora North America 1970; 21:544-5. [URL]
3. Ngozi N, Osuji T. Personal communication on the relevance and indigenous use of medicinal plants 2014.
4. Odugbemi T. Outlines and pictures of medicinal plants from Nigeria. University of Lagos Press, Lagos, Nigeria, 2006. P. 1-283. [URL]
5. Akinmoladun AC, Akinloye O. Effect of Chromolaena odorata on hypercholesterolemia-related metabolic imbalances. Proc. Akure-Humbold Kellog/3rd SAAT Annual Conference, FUTA, Nigeria, 2007; 287-90.
6. Muhammad Z, Mustafa AM. Traditional Malay Medicinal Plants. Fajar Bakti S/Bhd. 1994 [URL]
7. Phan TT, Lingzhi SP, Grayer RJ, Chan SY, Lee ST. Phenolic Compound of Chromolaena odorata Protect Cultured Skin Cells from Oxidative Damage: Implication for Cutaneous Wound Healing. Biol Pharm Bull 2001;24(12):1373-9 [DOI:10.1248/bpb.24.1373] [PMID]
8. Ling SK, Azah MA, Mastura M, Khoo MGH, Husni S, M. Salbiah, A. et al. Standardisation and formulation of Chromolaena odorata for herbal preparation. Identifying Potential Commercial Collaboratons Project Evaluation Meeting. 14-15 Dec 2005, FRIM. 2007.
9. Usunobun U, Ewere GE. Phytochemical analysis, Mineral Composition and in vitro antioxidant activities of Chromolaena odorata leaves. ARC J Pharma Sci 2016;2(2):6-10 [DOI:10.20431/2455-1538.0202003]
10. Gorlick R, Goker E, Trippett T, Waltham M, Banerjee B, Bertino JR. Intrinsic and acquired resistance to methotrexate in acute leukaemia. N Engl J Med 1996; 335:1041-8. [DOI:10.1056/NEJM199610033351408] [PMID]
11. Joerger M, Huitema AD, Illerhaus G, Ferreri AJ. Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma. Leuk Lymphoma 2012;53:1867-75. [DOI:10.3109/10428194.2012.676177] [PMID]
12. Tannock IF, Boyd NF, DeBoer G, et al. A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. J Clin Oncol 1988;6:1377-87. [DOI:10.1200/JCO.1988.6.9.1377] [PMID]
13. Widemann BC, Balis FM, Kempf-Bielack B, et al. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma: Incidence, treatment, and outcome. Cancer 2004;100:2222-32. [DOI:10.1002/cncr.20255] [PMID]
14. Vermorken JB, Specenier P. Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol 2010;21:252-61. [DOI:10.1093/annonc/mdq453] [PMID]
15. Haustein UF, Rytter M. Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatment. J Eur Acad Dermatol Venereol 2000;14:382-8. [DOI:10.1046/j.1468-3083.2000.00058.x] [PMID]
16. Helen STE, Schiano TD, Kuan SF, Hanauer SB, Conjeevaram HS, Baker AL. Hepatic effects of long term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol 2000;95:3150-6. [DOI:10.1111/j.1572-0241.2000.03287.x] [PMID]
17. Henderson ES, Adamson RH, Oliverio VT. The metabolic fate of tritiated methotrexate. II. Absorption and excretion in man. Cancer Res 1965;25:1018-24. [PMID]
18. Gibson EM, Nagaraja S, Ocampo A, Tam LT, Wood LS, Pallegar PN, Greene JJ, Geraghty AC, Goldstein AK, Ni L. Methotrexate chemotherapy induces persistent tri-glial dysregulation that underlies chemotherapy-related cognitive impairment. Cell 2019;176(1-2):43-55. [DOI:10.1016/j.cell.2018.10.049] [PMID] [PMCID]
19. Liu L, Liu S, Wang C, Guan W, Zhang Y, Hu W, Zhang L, He Y, Lu J, Li T. Folate supplementation for methotrexate therapy in patients with rheumatoid arthritis: a systematic review. J Clin Rheumatol 2019;25(5):197-202. [DOI:10.1097/RHU.0000000000000810] [PMID]
20. Abo-Haded HM, Elkablawy MA, Al-johani Z, Al-ahmadi O, El-Agamy DS. Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity. PLoS ONE 2017;12(3): e0174295. [DOI:10.1371/journal.pone.0174295] [PMID] [PMCID]
21. APA. Guidelines for Ethical Conduct in the Care and Use of Non-Human Animals in Research. American Psychological Association (APA), Washington DC, USA. 2012. [URL]
22. Aladaileh H, Saleem OE, Hussein MH, Abukhalil SAM, Saghir MB, Manal A. et al. Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats. Antioxidants 2019; 8:430. [DOI:10.3390/antiox8100430] [PMID] [PMCID]
23. Ijioma S, Okafor A, Ndukuba P, Nwankwo A, Akomas S. Hypogly¬cemic, hematologic and lipid profile effects of Chromolaena odorata ethanol leaf extract in alloxan induced diabetic rats. Ann Biol Sci 2014;2:27-32. [Google Scholar]
24. Fawcett JK, Scott JE. A rapid precise method for the determination of urea. J Clin Path 1960;13(2): 156-9. [DOI:10.1136/jcp.13.2.156] [PMID] [PMCID]
25. Ghasemi A, Azimzadeh I, Zahediasl S, Azizi F. Reference values for serum creatinine with Jaffe-compensated assay in adult Iranian subjects: Tehran Lipid and Glucose Study. Arch Iran Med 2014;17(6):394-9 [PMID]
26. Ohkawa H, Ohishi N, Yogi K. Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Ann Biochem 1979;95:351-8. [DOI:10.1016/0003-2697(79)90738-3] [PMID]
27. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972, 247:3170-5. [DOI:10.1016/S0021-9258(19)45228-9] [PMID]
28. Cohen G, Dembiee D, Marcus J. Measuremment of catalase activity in tissues extracts. Anal Biochem 1970;34: 30-8. [DOI:10.1016/0003-2697(70)90083-7] [PMID]
29. Arneson W, Brickell J. Assessment of renal function. In: (Arneson W, Brickell J, eds. Clinical Chemistry: A Laboratory Perspective. first ed. Philadelphia: F.A. Davis Company.; 2007. [URL]
30. Ferguson MA. Biomarkers of nephrotoxic acute kidney injury. Toxicology 2008;245(3): 182e193. [DOI:10.1016/j.tox.2007.12.024] [PMID] [PMCID]
31. Abouelela E Mohamed AA, Orabi RA. Abdelhamid MSA. Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, antiinflammatory, and antiapoptotic actions. J Trad Complement Med 2020;10:478-86. [DOI:10.1016/j.jtcme.2019.08.006] [PMID] [PMCID]
32. Usunobun U, Okolie PN. Dimethylnitrosamine (DMN) exposed rats: Vernonia amygdalina pretreatment enhances immunity hepatic and renal function. Int Biol Res 2016;4(1):17-20. [DOI:10.14419/ijbr.v4i1.5811]
33. Usunobun U, Okolie PN. Effect of Annona muricata pre-treatment on liver synthetic ability, kidney function and hematological parameters in dimethylnitrosamine (DMN)-administered rats. Int J Med 2016;4(1):1-5. [DOI:10.14419/ijm.v4i1.5709]
34. Sies H. Oxidative stress: introductory remarks. H. Sies, (Ed.). Oxidative Stress, Academic Press, 1985. P. 1-7. [DOI:10.1016/B978-0-12-642760-8.50005-3]
35. Usunobun U, Okolie NP. Synergistic, attenuative and modulatory activity in Dimethylnitrosamine (DMN)-induced fibrotic rats treated with Vernonia amygdalina and Annona muricata leaves. Nig J Pharma Appl Sci Res 2020;9(3):1-6 [URL]
36. Usunobun U, Okolie NP, Eze IG. Inhibitory Effect of Vernonia amygdalina on Dimethylnitrosamine (DMN)-induced Liver Fibrosis in Rats. Int J Clin Pharmacol Toxicol 2015;4(4):179-84. [DOI:10.14419/ijpt.v4i1.5785]
37. Kori-Siakpere O, Ubogu EO. Sublethal haematological effects of zinc on the freshwater fish, Heteroclarias sp. (Osteichthyes: Clariidae). Afr J Biotechnol 2008;7:2068-73. [DOI:10.5897/AJB07.706]
38. Arika W, Nyamai D, Musila M, Ngugi M, Njagi E. Hematological markers of in vivo toxicity. J Hematol Thromboembolic Dis 2016;4(2):4e10. [URL]
39. Mengiste B, Makonnen E, Urga K. In-vivo antimalarial activity of Dodonaea angustifolia seed extracts against Plasmodium Berghei in mice model. Afr J Online 2012;4:47-63. [DOI:10.4314/mejs.v4i1.74056]
40. Dacie JV, Lewis SM. Practical Haematology. 11th ed, Longman Group. Ltd. Hong Kong. 2001. P. 11-17. [URL]
41. Mcknight DC, Mills RG, Bray JJ. Human physiology, 4th ed. Churchhill Livingstone, 1999. P. 290-4.

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