Crassocephalum crepidioides (Ebolo) Protect against Paracetamol- Induced Hepatotoxicity in Wistar Rats

Fausat K. Ola Mudathir¹ , Ogheneoruese F. Onoharigho² , Sikirullai O. Jeje³ , Ighorhiowhoaro M. Ajekevwoda⁴

Section:Research Paper, Product Type: Journal-Paper
Vol.9 , Issue.4 , pp.23-29, Aug-2022

Online published on Aug 31, 2022

Copyright © Fausat K. Ola Mudathir, Ogheneoruese F. Onoharigho, Sikirullai O. Jeje, Ighorhiowhoaro M. Ajekevwoda . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

View this paper at   Google Scholar | DPI Digital Library

XML View     PDF Download

How to Cite this Paper

Abstract :
Paracetamol causes hepatocellular damage due to increase oxidative stress, whereas Crassocephalum crepidioides enhances antioxidant status. The preventive function of Crassocephalum crepidioides against paracetamol (PCM)-induced hepatocellular oxidative damage was studied. The experiment was made up of four groups (1, 2, 3, and 4) of Wistar rats (n=6). The control (Group 1) were given distilled water while groups 2 and 3 animals were given 300mg/kg bwt/day methanol extract of C. crepidioides leaves (MECL) and 250 mg/kg bwt/day PCM respectively for two weeks. Group 4 was given (MECL) for one week and thereafter a concurrent dose of 300 mg per kg bwt each day (MECL) and 250 per kg bwt each day PCM for two weeks. All administration was done orally. The evaluation of serum aspartate amino transferase (AST) and Alanine amino transferase (ALT) activities were carried out to detect liver injury. Glutataione-s-transferase (GST), superoxide dismutase (SOD), catalase activities and reduced glutathione (GSH) level were utilized to measure antioxidant status. Malondialdehyde (MDA) level was employed as an indication of lipid peroxidation. The results indicated an increase (p< 0.05) in the activities of serum AST, ALT and MDA level in the PCM group. The activities of GST, SOD, catalase and level of GSH were significantly lowered (p< 0.05) relative to control. Concurrent treatment with PCM and C. crepidioides considerably decreased (p< 0.05) MDA level, AST and ALT activities but significantly increased (p< 0.05) the antioxidant enzymes compared to PCM group. Finally, Crassocephalum crepidioides may protect Wistar rat’s liver against paracetamol-induced oxidative damage.

Key-Words / Index Term :
Antioxidant, Crassocephalum crepidioides, Liver damage, Paracetamol

References :
[1] M. Thompson, Y. Jaiswal, I. Wang, and L. Williams, “Hepatotoxicity: Treatment, Causes and Applications of Medicinal Plants as Therapeutic Agents,” Elsevier Science, Vol.6, No.3, pp. 186–193, 2017.
[2] S. Appak-Baskoy, C. Mustafa, T. Ozgun, and A. Adnan, “Dietary Antioxidants in Experimental Models of Liver Disease,” Intechopen, Vol.83485, pp.1-22, 2019.
[3] M. Castañeda-Juárez, L.A. Castillo-Suárez, V. Martínez-Miranda., P.T. Almazán-Sánchez, I. Linares-Hernández, V. Lugo-Lugo, M. Esparza-Soto, F. Santoyo-Tepole. “Oxidation of N-acetyl-para-aminophenol (acetaminophen) by a galvanic Fenton and solar galvanic Fenton processes,” Solar Energy, Vol.199, pp.731-741. 2020.
[4] M. Jozwiak- Bebenista, and J. Z. Nowak, “Paracetamol: Mechanism of Action, Applications and Safety Concern,” Acta Poloniae Pharmaceutica - Drug Research, Vol.71, No.1, pp.11–23, 2014.
[5] L. L. Mazaleuskaya, K. Sangkuhl, C. F. Thorn, G. A. FitzGerald, R. B. Altman, and T. E. Klein, “PharmGKB Summary: Pathways of Acetaminophen Metabolism at the Therapeutic Versus Toxic Doses,” Pharmacogenetics and Genomics, Vol. 25, No. 8, pp. 416–426, 2015.
[6] S. Ilavenil, N. Al-Dhabi, S. Srigopalram, Y. Ock Kim, P. Agastian et al., “Acetaminophen Induced Hepatotoxicity in Wistar Rats—A Proteomic Approach,” Molecules, Vol.21 No.2, pp. 161, 2016.
[7] M. Barbara, v. Vugt-Lussenburg, L. Capinha, J. Reinen, M. Rooseboom, M. Kranendonk, R. C., Onderwater, and P. Jennings. “Commandeuring” Xenobiotic Metabolism: Advances in Understanding Xenobiotic Metabolism,” Chemical Research in Toxicology, Vol. 35, Issue 7, pp. 1184-1201, 2022.
[8] C. V. Sharma, V. Mehta, “Paracetamol: Mechanisms and Updates,” Continuing Education in Anaesthesia Critical Care & Pain, Vol.14, No.4, pp.153–158, 2014.
[9] D. Kumar, S. Kumar and C. Shekhar. “Nutritional Components in Green Leafy Vegetables: A Review,” Journal of Pharmacognosy and Phytochemistry, Vol. 9 Issue 5, pp2498-2502, 2020
[10] L. T. Ngo, J. I. Okogun, and W. R. Folk, “21st Century Natural Product Research and Drug Development and Traditional Medicines,” Natural Product Reports, Vol.30, No.4, pp.584, 2013.
[11] S. Schramm, W. Rozhon, A. N. Adedeji-Badmus, Y. Liang, S. Nayem, T. Winkelmann and B. Poppenberger, “The Orphan Crop Crassocephalum crepidioides Accumulates the Pyrrolizidine Alkaloid Jacobine in Response to Nitrogen Starvation,” Front Plant Sci., Vol. 12, 702985, 2021.
[12] S.T. Thoudam. Development of an Herbal Syrup Using Leaves Extract of Crassocephalum crepidioides. Nairobi Journal of Food Science and Technology, Vol.1, No.1, 2020.
[13]O.M. Bello, B.O. Abiodun, A.U. Uduma, “Antioxidant and Lipoxygenase Inhibitory Activity of Crassocephalumcrepidioides (Benth.) S. Moore; an underutilized vegetable from Nigeria,” FRsCS, Vol.1, No.2, pp.28–31, 2019.
[14] G.A. Mahmoudi, P. Astaraki, A. Zafar Mohtashami, M. Ahadi, “N-acetylcysteine Overdose After Acetaminophen Poisoning,” International Medical Case Reports Journal, Vol.11, pp.65-69, 2015.
[15] G. Karthivashan, A. U. Kura, P. Arulselvan, N. Md. Isa, and S. Fakurazi, “The modulatory Effect of Moringaoleifera Leaf Extract on Endogenous Antioxidant Systems and Inflammatory Markers: an Acetaminophen-Induced Nephrotoxic Mice Model,” PeerJ, Vol. 4, pp.2127, 2016.
[16] S. O. Salawu, and A. A. Akindahunsi, “Protective Effect of Some Tropical Vegetables against CCl4 -Induced Hepatic Damage,” Journal of Medicinal Food, Vol.10, No.2, pp. 350-355, 2007.
[17] Laura Rotundo and Nikolaos Pyrsopoulos, “Liver Injury Induced by Paracetamol and Challenges Associated with Intentional and Unintentional Use,” World J Hepatol. Vol.12, No. 4, pp.125–136, 2020.
[18] M. Yan, Y. Huo, S. Yin, H. Hu, “Mechanisms of Acetaminophen-induced Liver Injury and its Implications for Therapeutic Interventions,” Redox Biology, Vol.17, pp.274-283, 2018.
[19] N. D. Mahmood, S. S. Mamat, F. H Kamisan et al., “Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Methanol Extract of Muntingiacalabura L. Leaves,” BioMed Research International, Vol.2014, pp. 1-10, 2014.
[20] S. A. Wicaksono S. B. UtamiP. D. PitalokaM. Hapsari, “The Effect of Paracetamol and Morphine Analgesic Combination on Serum Aspartate Aminotransferase and Alanine Aminotransferase Levels in Male Wistar Rats,” Pakistan Journal of Medical and Health Sciences Vol.13, No.4, pp. 1253-1258, 2019.
[21] O. Oladeji, “The Characteristics and Roles of Medicinal Plants: Some Important Medicinal Plants in Nigeria,” Nat Prod Ind J., Vol.12, No.3, pp.102, 2016.
[22] A.A. Adjatin, C.S. Dansi, P. Eze, I. Assogba, K. Dossou-Aminon, A. Akpagana, Akoegninou, A. Sanni, “Ethanobotanical Investigation and Diversity of Gbolo [Crassocephalumrubens (Juss. Ex Jacq). S. Moore and C.crepidioides (Benth) S. Moore], a Traditional Leafy Vegetable under Domestication in Benin,” Genet. Resour Crop Evol., Vol.59, No.8, pp.1867-1881, 2012.
[23] E. Bahar, M. S. Siddika, B. Nath and H. Yoon, “Evaluation of In vitro Antioxidant and In vivo Antihyperlipidemic Activities of Methanol Extract of Aerial Part of Crassocephalumcrepidioides (Asteraceae) Benth S Moore”, Tropical Journal of Pharmaceutical Research, Vol.15, No.3, pp.481-488, 2016.
[24] O. B. Adewale, A. Onasanya, S. O. Anadozie, C. J. Ogbole, I. A. Akintan, M. F. Abu, “Protective Effect of Ethanolic Extract of Crassocephalum Rubens Leaves on Carbon Tetrachloride - Induced Liver Damage in Rats,” World Journal of Pharmaceutical Research, Vol.4, No.2, pp.156-168, 2015.
[25] J.A. Buege, and S.D. Aust, “Microsomal Lipid Peroxidation Methods,” Enzymol., Vol.52, pp.302 – 310, 1978.
[26] H.P. Misra, and I. Fridovich, “The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase”, Journal of biological chemistry, Vol. 247, pp.3170-3175, 1972.
[27] W.H. Habig, M.J. Pabst, and W.B. Jakoby, “Glutathione S-transferases; “The First Enzymatic Step in Mercapturic Acid Formation”, Journal of biological chemistry, Vol. .249, pp.7130-7139, 1974.
[28] E. Beutler, O. Duron, and B.M. Kelly, “Improved Method for the Determination of Blood Glutathione,” J. Lab. Clin. Med., Vol.61, pp.882-888, 1963.
[29] A.K. Sinha, “Colorimetric Assay of Catalase,”. Anal. Biochem., Vol.47, pp.389-394, 1971.
[30] R. Twycross, V. Pace, M. Mihalyo, and A. Wilcock, “Acetaminophen (Paracetamol),” Journal of Pain and Symptom Management, Vol.46, pp. 47–755, 2013.
[31] E. Yoon, A. Babar, M. Choudhary, M. Kutner, and N. Pyrsopoulos, “Acetaminophen-Induced Hepatotoxicity: A Comprehensive Update,” Journal of Clinical and Translational Hepatology, Vol.4, pp.131–142, 2016.
[32] G. W. Przyby?a, K. A. Szychowski, and J. Gmi?ski, “Paracetamol ?an old Drug with New Mechanisms of Action,” Clinical and Experimental Pharmacology and Physiology, Vol. 48, No. 1, pp. 3-11, 2020.
[33] S. Robin, K. Sunil, A. C. Rana, and S. Nidhi, “Different Models of Hepatotoxicity and Related Liver Diseases: A Review,” International Journal of Pharmaceutical Research and Review, Vol. 3, pp. 86–95, 2012.
[34] N. S. Uchida, E. S. Saulo, F. E. C. Gabriel et al., “Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice,” Evidence-Based Complementary and Alternative Medicine, Vol.2017, pp.1-9, 2017.
[35] E. S. Omoregie, O. T. Okugbo, E. Oikeh and S. Irabor, “Hepatoprotective Effect of Leaf Extracts of Crassocephalum rubens (Juss. ex Jacq.) S. Moore in Rrifampicin-induced Oxidative Stress in Swiss Mice,” Journal of Pharmacy and Bioresources, Vol. 12, No. 2, 2015.
[36] R. N. Hota, B. K. Nanda, B. R. Behera and A. Bose. “Ameliorative Effect of Ethanolic Extract of Limnophila rugosa (Scrophulariaceae) in Paracetamol- and Carbon Tetrachloride-Induced Hepatotoxicity in Rats.” Future Journal of Pharmaceutical Sciences Vol. 8, No 6, pp. 1-16, 2022
[37] V.I Lushchak, “Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions,” Journal of Amino Acids, Vol. 2012, pp. 1-7, 2012.
[38] M. R. McGill, M. R. Sharpe, C. D. Williams, M. Taha, S. C. Curry, and H. Jaeschke, “The Mechanism Underlying Acetaminophen-Induced Hepatotoxicity in Humans and Mice Involves Mitochondrial Damage and Nuclear DNA Fragmentation,” Journal of Clinical Investigation, Vol. 122, pp. 1574–1583, 2012.
[39] O. Arinola, O. Ochuko L. Erukainure, C. Ibeji, N. A. Koorbanally, M.S. Islam. “Crassocephalum rubens, a Leafy Vegetable, Suppresses Oxidative Pancreatic and Hepatic Injury and Inhibits Key Enzymes Linked to Type 2 Diabetes: An Ex Vivo and in Silico Study,”. Journal of Food Chemistry, Vol.,43 Issue 8, 2019.
[40] T. F. Salisu, B. O. Ottu, A. K. Oloyo, J. E. Okpuzor and S. I. Jaja. “Assessment of Wild African Vegetables on Cardiac Functions, Antioxidants and Blood Lipid Profile in a Rat Model of Myocardial Infarction,” FUW Trends in Science & Technology Journal Vol.7 No. 1, pp. 070 – 082, 2022.
[41] H. Jaeschke, M. R. McGill, and A. Ramachandran, “Oxidant Stress, Mitochondria and Cell Death Mechanisms in Drug-Induced Liver Injury: Lessons Learned from Acetaminophen Hepatotoxicity,” Drug Metabolism Reviews, Vol.44, pp.88–106, 2012.
[42] G. Oboh, G. M. Busari, A. O. Ademosun, S. I. yeleye, “Effect of Dietary Inclusion of Fireweed (Crassocephalumcrepidioides) on Behavioural Patterns, Memory Indices, and Activities of Cholinergic and Monoaminergic Enzymes In a Fruit Fly (Drosophila melanogaster) Model of Alzheimer`s Disease,” Food Frontiers, pp. 1-12, 2021.
[43] H. Younus, “Therapeutic potentials of superoxide dismutase,” International Journal of Health Sciences (Qassim), Vol.12, No. 3, pp.88–93, 2018.
[44] A. Nandi, Y. Liang-Jun,C. K. Jana,and D. Nilanjana, “Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases,” Vol.2019, pp. 1-19, 2019.
[45] D. A. Cherian, T. Peter, A. Narayanan, S. S. Madhavan, S. Achammada, and, G. P. Vynat, “Malondialdehyde as a Marker of Oxidative Stress in Periodontitis Patients,” Journal of Pharmacy and Bioallied Sciences, Vol.11, No.2, pp.297-300, 2019.
[46] S. S. Tripathi, S. Singh, G. Garg et al., “Metformin Ameliorates Acetaminophen-induced Sub-Acute Toxicity Via Antioxidant Property,” Drug and chemical toxicology, Vol.45, No, 1, pp. 1-9, 2019.
[47] I. M. Merdana, N. L. Watiniasi, I.W Sudira, and Samusuri, “The Effect of Ethanol Extract of Mymercodia Pendas on Paracetamol-Induced Hepatotoxicity in White Rats. IOP Conference series,” Earth and Environmental Science, Vol.248, No.1, pp. 2-9, 2019.
[48] M. Samiha, “Phytochemical and Pharmacological Evaluation of Crassocephalum crepidioides,” pp. 5-68, 2019.