Effects of Carica papaya Seeds on Acetaminophen-Induced Hepatotoxicity in Male Wistar Rats
doi.org/10.26538/tjnpr/v4i8.23
Keywords:
Extract, Carica papaya Linn, Hepatotoxicity, AcetaminophenAbstract
Acetaminophen is an analgesic drug used commonly in clinics. However, it causes acute liver failure with continuous overdose. The present study was designed to investigate the effects of Carica papaya seeds on acetaminophen-induced hepatotoxicity in male Wistar rats. Thirty-six male Wistar rats were divided into four groups: Control group (NC), positive control (PC), 1000 mg/kg and 500 mg/kg of nine animals each. The PC, 1000 mg/kg and 500 mg/kg groups were given a dose of acetaminophen (2500 mg/kg b.w) orally, and after day three, three rats (n=3) were taken at random from each group and serum enzymes activity levels of Aspartate aminotransferase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) were assessed to ascertain hepatotoxicity. Afterwards, rats were treated with Carica papaya seeds extract (1000 mg/kg and 500 mg/kg) for fourteen days. The rats were euthanized, plasma collected and analysed for biochemical parameters, while liver tissues were examined for histopathological changes. There was a significant decrease (p < 0.05) in ALT, gamma-glutamyl transferase (ɤ-GT), globulin and reduction in Malondiadehyde.(MDA) concentrations in both 500 mg/kg and 1000 mg/kg groups compared to the PC group. However, serum albumin, total protein and superoxide dismutase (SOD) increased toward normal level in the treated groups. Histopathological studies showed improvement in the liver architecture in the 500 mg/kg group. The increase in endogenous antioxidants and reduction in lipid peroxidation observed in this study suggests that Carica papaya seeds extract can be used as a natural antioxidant in handling liver injury potentiated by acetaminophen overdose.
References
Olorunisola OS, Aintola AO, Afolayan AJ. Hepatoprotective and antioxidant effect of Sphenocentrum jollyanum (Menispermaceae) stem bark extracts against CCl4- induced oxidative stress in rat. Afr J Pharm Pharmacol. 2011; 5(9):1241-1246.
Deaval GD, Elizabeth AM, Judith MH, Ruth R. Druginduced oxidative stress and toxicity. J Toxicol. 2012; 6:10- 16.
Navarro VJ and Senior JR. Drug-related hepatotoxicity. New Eng J Med. 2006; 354:731-739.
Woolbright BL and Jaeschke H. Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. J Hepatol. 2017; 66(4):836–848.
Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: an updated review. Arch Toxicol. 2014; 89(2):193–199.
Kane AE, Mitchell SJ, Mach J. Acetaminophen hepatotoxicity in mice: effect of age, frailty and exposure type. Exp Gerontol. 2016; 73(3):95–106.
Eugenio-P´erez D, Montes de Oca-Solano HA, PedrazaChaverri J. Role of food-derived antioxidant agents against acetaminophen-induced hepatotoxicity. Pharm Biol. 2016; 54(10):2340–2352.
Ekpenyong CE, Akpan E, Nyoh A. Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon citratus (DC.) stapf extracts. Chin J Nat Med. 2015; 13(5):321–337.
Athesh K, Karthiga D, Brindha P. Anti-obesity effect of aqueous fruit extract of Carica papaya Linn in rats fed on high fat cafeteria diet. Asian J Pharm Clin Res. 2017; 10(4): 384-390.
Jaiswal P, Kumar P, Singh VK, Singh DK. Carica papaya Linn: a potential source for various health problems. J Pharm Res. 2010; 3(5):998-1003.
Krishna KL, Paridhavi M, Patel JA. Review on nutritional, medicinal and pharmacological properties of papaya (Carica papaya Linn.). Nat Prod Rad. 2008; 7(4):364-373.
Zhou K, Wang HW, Mei W, Li X, Luo y, Dai H. Antioxidant activity of papaya seed extracts. Mol. 2011; 157:203-207.
Madinah N, Nozmo M, Ezekiel L. The protective effects of aqueous extract of Carica Papaya seeds in paracetamolinduced nephrotoxicity in male Wistar rats. Afr H Sci. 2015; 5(2):598-605.
Adeneye AA, Olagunju JA, Banjo AA, Abdul SF, Sanusi OA, Sanni OO, Osarodion BA, Shonoiki OE. The Aqueous Seed Extract of Carica papaya Linn. Prevents Carbon Tetrachloride Induced Hepatotoxicity in Rats. Int J Appl Res Nat Prod. 2009; 2(2):19-32.
Francis VU and Paul BU. Hepatotoxicity of the Methanol Extract of Carica papaya. (Paw-Paw) Seeds in Wistar Rats. Pharm Biol. 2005; 43(4):349-352.
OECD Acute oral toxicity: Up and down procedure Guideline for the Testing of Chemicals, 425, OECD 2008. 1-27 p.
Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis: Protective role of glutathione. J Pharmacol Exp Ther. 1973; 187:211-217.
Ghanem CI, Perez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: new insights into drug pharmacological action and toxicity. Pharmacol Res. 2016; 109:119-131.
Yahya F, Mamat SS, Kamarolzaman MF. Hepatoprotective activity of methanolic extract of Bauhinia purpura leaves against Acetaminophen-induced hepatic damage in rats. Evid-Based Compl Altern Med. 2013; Article ID 636580.
Bhattacharjee R and Sil PC. The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen-induced hepatic disorder via its antioxidant properties. Phytother Res. 2006; 20(7):595-601.
Nancy SU, Saulo ES, Gabriel FE, Edivaldo C, Francielli MS, Expedito LS. Hepatoprotective. Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice, Evid Based Compl Altern Med. 2017. Article ID 1796209.
Jun NH, Xing YX, Wei L, Yi-Ming W, Ying L, Zi W, Ying-ping W. Ginsenoside Rk1 ameliorates paracetamolinduced hepatotoxicity in mice through inhibition of inflammation, oxidative stress, nitrative stress and apoptosis. J Ginseng Res. 2017; 43:10-19.
Thapa BR and Walia A. Liver function tests and their interpretation. Ind J Pedia. 2007; 74:663-667.
Alkiyumi SS, Abdullah MA, Alrashdi AS, Salama SM, Abdelwahab SI, Hadi HA. Ipomoea aquatic extract shows protective action against thioacetamide-induced hepatotoxicity. Mol. 2012; 17(5):6146-6155.
Green TJ, Sivilotti ML, Langmann C. When do the aminotransferases rise after acute acetaminophen overdose? Clin Toxicol. 2010; 48(8):787–792.
Rasool MK, Sabina EP, Ramya SR, Preety P, Patel S, Mandal N. Hepatoprotective and antioxidant effect of gallic acid in Acetaminophen-induced liver damage in mice. J Pharmacol. 2010; 62:638-643.
Okokon JE, Udobang JA, Bassey AI, Edem UA, Agu EC. Hepatoprotective and Nephroprotective Activities of Husk Extract of Zea mays Against Paracetamol-Induced Liver and Kidney Injuries in Rats. Trop J Nat Prod Res. 2020; 4(3):67-76.
Shi C, Zhao X, Liu Z, Meng R, Chen X, Guo N. Antimicrobial, antioxidant, and antitumor activity of epsilonpoly-L-lysine and citral, alone or in combination. Food Nutr Res. 2016; 60:31891.
Freitag FA, Cardia GF, Rocha DA. Hepatoprotective effect of silymarin (Silybum marianum) on hepatotoxicity induced by acetaminophen in spontaneously hypertensive rats. Evid. Based Compl Altern Med. 2015; Article ID 538317.
Madrigal-Santill´an E, Madrigal-Bujaidar E, AlvarezGonz´alez I. Review of natural products with hepatoprotective effects. World J Gastroenterol. 2014; 20(40):14787–14804.
Ekam VS and Udosen EO. Total protein, albumin and globulin levels following the administration of activity directed fractions of Vernonia amygdalina during acetaminophen-induced hepatotoxicity in Wistar albino rats. Global J Pure Appl Sci. 2012; 18:25-29.
Ramadan KS, Khalil OA, Danial EN, Alnahadi HS, Ayaz NO. Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats. J Physiol Biochem. 2013; 69:779–783.
Kaplan LA and Pesce AJ. Clinical chemistry. (3rd ed.) St. Louis, MO: Mosby. 1996. 517 p.
Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on Acetaminophen-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol. 2010; 48
(11):3246-3261.
Omidi A, Riahinia N, Montazer Torbati MB, Behdani MA, Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna J Phytomed. 2014; 4(5):330-336.
El Morsy EM and Kamel R. Protective effect of artichoke leaf extract against paracetamol-induced hepatotoxicity in rats. Pharm Biol. 2015; 53:167–173.
Sathya A and Siddhuraju P. Protective effect of bark and empty pod extracts from Acacia auriculiformis against paracetamol intoxicated liver injury and alloxan-induced type II diabetes. Food Chem Toxicol. 2013; 56:162-170.
Elisan P, Majdi D, Stefania M, Cristian V, Luciana D. Administration dependent antioxidant effect of Carica Seeds Water Extract. Evid Based Compl Altern Med. 2014; Article ID 281508.
Jaeschke H, McGill MR, Ramachandran A. Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev. 2012; 44:88–106.
Olufunsho A, Omoniyi Y, Peter UI, Victor OI. Modulatory potentials of aqueous leaf and unripe fruit extracts of Carica papaya Linn. (Caricaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats. J Intercult Ethnopharmacol. 2016; 5(1):27-35.
Dadkhah A, Fatemi F, Alipour M, Ghaderi Z, Zolfaghari F, Razdan F. Protective effects of Iranian Achillea wilhelmsii essential oil on acetaminophen-induced oxidative stress in rat liver. Pharm Biol. 2015; 53(2):220-227.
Bajpai J, Prakash V, Kant S, Verma AK, Srivastava A, Bajaj DK, Ahmad MK, Agarwal A. Study of oxidative stress biomarkers in chronic obstructive pulmonary disease and their correlation with disease severity in north Indian population cohort. Lung India. 2017; 34:324–329.
Sharma A, Sharma MK, Kumar M. Modulatory role of Emblica officinalis fruit extract against arsenic-induced oxidative stress in Swiss albino mice. Chem Biol Interact. 2009; 180:20–30.
Hsu YW, Tsai CF, Chen WK, Lu FJ. Protective effects of seabuckthorn (Hippophae rhamnoides L.) seed oil against carbon tetrachloride-induced hepatotoxicity in mice. Food Chem Toxicol. 2009; 47:2281-2288.
Benkhassi Z, Lahlou FA, Hmimid F, Loutfi M, Benaji B, Bourhim N. Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen. Am J Biomed Res. 2013; 1(4):75-79.
YQ Ma, Fang ZX, Chen JC, Xu CH, Liu DH. Phenolic compounds and antioxidant activity of extracts from ultrasonic treatment of Satsuma mandarin peels. J Agric Food Chem. 2008; 56:5682-5690.
Zhang ZT, Liao LP, Moore J, Wu T, Wang ZT. Antioxidant phenolic compounds from walnut kernels (Juglans regia L). Food Chem. 2009; 113:160-165.
Okpo SO, Falodun A, Inegbenebor ME, Eze GI. Hepatoprotective effect of 3-carbomethoxylpyridine isolated from Pyrenacantha staudtii (Icacinaceae) leaves on carbon tetrachloride-induced liver damage. Nig J Pharm Sci. 2013; 12(1):55-65.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
