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Acetaminophen, used for antipyretic and analgesic purposes has been known to exhibit toxic effects on the organs because of its ability to generate free radicals, causing varieties of diseases. This study investigated the impact of the combined formed of Garcinia kola seed and Vitamin E pretreatment exposure on hepatotoxicity and oxidative stress induced by acetaminophen in Albino Rats. Five groups of animals were used for this study. Group 1 as the control received distilled water orally only, group 2 as toxicity control intoxicated with 800 mg acetaminophen intraperitoneally. The other three groups were pretreated with various doses of either Garcinia kola seed extract or vitamin E or a combined form respectively by oral gavage method for 7 days before induction with acetaminophen intraperitoneally on the 8th day and sacrificed under chloroform anaethesia. Acetaminophen induction significantly rise (p<0.05) the hepatic enzyme levels (ALT, AST, and ALP) and a marked reduction of the antioxidant enzymes (SOD, CAT and GPX) in group 2 animals when compared with the control. There was also a significant rise (p<0.05) in the MDA levels. Meanwhile the combined form of Garcinia kola seed extract and Vitamin E pretreatment exposure on the organs showed no synergetic ameliorative potentials as compared with the single pretreatment exposure with Garcinia kola and Vitamin E respectively. The morphology of the tissue cells pretreated with these combined formed exhibited features showing signs of cell damages and slow recovery from the toxicity. Therefore combining Garcinia kola and Vitamin E may lost its ameliorative and protective effect as seen in this induced acetaminophen albino rats implying that Garcinia kola seed and Vitamin E should not be taken in a combined form.
Adegboye MF, Akinpelu DA, Okoh AI. The bioactive and phytochemical properties of Garcinia kola (Heckel) seed extract on some pathogens. African Journal of Biotechnology. 2008;7(11):3934-3938.
Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more. Free Radical Biology & Medicine. 2007;43(1):4-15.
Pawan K, Verma M, Sultana R, Raina S, Praws S, Pandita NJ, Arshad HM. Hepatoprotective effects of Ageratum canyzoides L on biochemical indices induced by acetaminophen toxicity in wistar rats. Journal of Applied Pharmaceutical Science. 2013;3(4):523– 527.
Lead AM, Begona Ruiz-Larrea M, Martinez R, Lacort M. Cytoprotective actions of estrogens against tert-butyl hydroperoxide-induced toxicity in hepatocytes. Biochemical Pharmacology. 1998;56:1463-1469.
Lewerenz V, Hanett S, Nasterska C, El-Balay C, Rohrdanz E, Kahl R. Antioxidant protect primary rate Hepatocytes cutures against acetaminophen-induced DNA strand breaks but not against acetamino-phen-induced cytotoxicity. Toxicology. 2003;191:179–187.
Sin B, Wai M, Tatunchak T, Motov SM. The use of intravenous acetaminophen for acute pain in the emergency department. Academic Emergency Medicine. 2016;23: 543–53.
Nelson SD. Molecular mechanisms of the hepatotoxicity caused by acetaminophen. Seminar on liver Disease. 1990;10:267-278.
Dahlin DC, Miwa GT, Lu AY, Nelson SD. N-acetyl-P-benzoquinone imine: A cytochrome P-450-mediated oxidation product of acetaminophen. Proceedings of the National Academic of Science. 1984; 81:1327-1331.
Vermeulen NPE, Bessems JGM, Vande Streat R. Molecular aspects of paracetamol induced hepatotoxicity and its mechanism based prevention. Drug Metabolism and Revolution. 1992;24:367-457.
Hinston JA, Reid AB, McCullough SS, James LP. Acetaminophen-induced hepatotoxicity: Role of metabolic activation, reactive oxygen/ nitrogen species, and mitochondrial permeability transition. Drug Metabolism Revolution. 2004;36:805-822.
Tiwari A. Imbalance in antioxidant defense and human diseases: Multiple approach of natural antioxidants therapy. Current Science. 2001;81:1179–1187.
Karber G. Beitrag zur kollecktiven Behandlung pharmakologischer Reihenversuche. Achives of Experimental Pathology and Pharmacokology. 1931;162: 480-483.
Lorke D. A new approach to practical acute toxicity testing. Archives of Toxicology. 1983;54:275-287.
PHS. Public health service policy on humane care and use of laboratory animals. Publication of the Department of Health and Human Services. National Institute of Health. Office of Laboratory Animal Welfare; 2015.
ILAR. Guideline for the care and use of laboratory animal. 8th edition. National academic Press. Washington D.C; 2011.
OLAW. Institution Animal care and use committee Guidebook. 2nd edition NIH publication. Besthesda. 2002;1-230.
OECD/OCDE. Guideline for testing of chemical, acute oral toxicities, up and down Procedure. 2001;425:1-26.
Dede EB, Kagbo HD, Igbigbi PS. Determination of LD50 value of Metekelfin in rats. Journal of Science and Meta Science. 1997;1:1-7.
Ganie SA, Zargar A, Mosood MA. Hepatoprotective and antioxidant activity of rhizome of Podophyllum hexandrum against carbon tetrachloride-induced hepato-toxicity in rats. Biomedical Environmental Science. 2013;26(3):209-221.
Ven Kumar MR, Latha MS. Hepatoprotective effect of the methanolic extract of Curculigo orchioides in CCL4-treated male rats. Indian Journal of Clinical Biochemistry. 2002;17-2:80-87.
AVMA. Guidelines for euthanasia of animals. American Vertinary Medical Association. 2013;1-102.
Reitman S, Frankel S. A colorimetric method for determination of serum glutamate oxaloacetate and glutamic pyruvate transaminase. American. Journal of Clinical. Pathology. 1957;28:56-58.
Chuku LC, Uwakwe AA, Chinaka NC. Liver enzymes in normal and sickle cell subjects. Journal of Natural Science Research. 2012;2(7):1-4.
Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of Serum albumin with bromocresol green. Clinica Chimica Acta. 1971;31:87-96.
Flack CP, Wollen JW. Prevention of interference by Dextran with Biuret- type Assay of serum proteins. Clinical Chemistry. 1984;30(4):559-561.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 1979;95(2):351-358.
Aebi H. Aebi H (ed) Catalase in vitro. Methods in Enzymology. 1984;105:121-126.
Misra HP, Fridovich I. The role of superoxide anion in the antioxidation of epinephrine and a simple assay of Superoxide Dismutase. Journal of Biological Chemistry. 1972;247:3170-3175.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of Glutathione peroxidase. Science. 1973;179(4073):588-590.
Akintowa A, Essien AR. Protective paracetamol-induced hepatotoxicity in rats. Journal of Ethnopharmacology. 1990;29: 207-211.
Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: An updated review. Achives of Toxicology. 2015;89(2): 193-197.
Rakapoor B, Venugopal Y, Anbu J, Harikrishinah N, Gobinath M, Ravichandran V. Protective effect of Phyllanthus polyphyllus on acetaminophen induced hepatotoxicity in rats. Pakistan Journal of Pharmaceutical Science. 2008; 21(1):57-62.
Rajesh SV, Rajkapoor B, Kumar S, Raju K. Effect of Clausena dentate(willd) M. roem. against paracetamol induced hepato-toxicity in rats. Pakistan Journal of Pharmacological Science. 2009;22(1):90-93.
Moore M, Thor H, Moore G, Nelson S, Moldeus P, Orrenius S. The toxicity of acetaminophen and N. acetyl P-benzo-quinoneimine in isolated hepatocyte associated eith the depletion and increased cystosolic Ca2+. Journal of Biological Chemistry. 1985;260:13035-13040.
Kaplan MM. Laboratory tests. In: Schiff L., Schiff, E.R eds. Disease of the liver, 7th edition. Philadephia, J. B. Lippincott; 1993.
Jesse B. Animal anatomy and physiology. USA, Reston publishing Company; 1982.
Iwu MM, Igboko OA, Tempesta MS. Biflavanoids constituents of Garcinia kola root. Fitoterapia. 1990;61:178-181.
Thabrew M, Joice P. A comparative study of the efficacy of Pavetta indica and Osbeckia octanda in the treatment of liver dysfunction. Planta Medicine. 1987;53: 239–241.
Braide VP. Antihepatotoxic biochemical effects of kolaviran, a biflavonoid of Garcinia kola seeds. Phytotherapy Research. 1991;5:35-37.
Omage K, Erifeta OG, Uhunmwangho SE, Sunday JJ, Kazeem AO. Evaluation of hypoglycemic and antioxidative properties of aqueous extract of Garcinia kola seeds in wistar rats. Current Research Journal of Biological Science. 2011;3(4):326-329.
Terashima K, Takawa Y, Niwa M. Powerful
antioxidative agents based on Garcinonic acid from Garcinia kola. Biorganic Medi-cinal Chemistry. 2002;10(16):19-1625.
Trible DL, Aw TY, Jones DP. The pathophysiological significance of lipid peroxidation in oxidative cell injury. Hepatology. 1987;7:377-387.
Edwin HO, Keyvan KG, Chia-Chi L, Ravi B, Gemma AF. Biological markers of oxidative stress: Applications to cardiov-ascular research and practice. Redox Biology. 2013;1:483-491.
Sies H. Oxidative stress, strategies of antioxidant defense. European Journal of Biochemistry. 1993;215:213-219.
Morakinyo AO, Iranloye BO, Oyelowo OT, Nnaji J. Antioxidative and hepatoprotective effect of beta carotene on acetaminophen induced liver damage in rats. Biology and Medicine. 2012;4(3):134-140.
Devaki T, Raghavendran HRB, Sathivel A. Hepatoprotective nature of seaweed alcoholic extract on acetaminophen induced hepatic oxidative stress. Journal of Health Science. 2004;50:42-46.
Michel F, Bonnefont-Rousselot D, Mas E, Drai J, Therond P. Biomarkers of lipid peroxidation: Analytical aspects. Annals of Biological Clinic. 2008;66:605-620.
Johnson F, Giulivi C. Superoxide dismutases and their impact upon human health. Molecular Aspects of Medicine. 2005;26:340-352.
Adedara IA, Awogbindin IO, Anamelechi JP, Farombi EO. Garcinia kola seed ameliorates renal, hepatic and testicular oxidative damage in streptozotocin –induced diabetic rats. Pharmaceutical Biology. 2015;53(5):695-704.
Wegwu, MO, Didia BC. Hepatoprotective effect of Garcinia kola seed against hepatotoxicity induced CCl4 in rats. Biochemistry. 2007;19(1):17-21.
Tain YL, Freshour G, Dickalova A, Griendlira K, Baylis C. Vitamin E reduces glomerulosclerosis, restores renal neuronal NOS and suppresses oxidative stress in the 5/6 nephrectomized rat. American Journal of Physiological Renal Physiology. 2007;292(5):F1404-F1410.
Boyd EM, Bereckzky GM. Liver damage from paracetamol. British Journal of Pharmacology. 1996;26:606.
Garba AM, Mohammed B, Garba SH, Numan AL, Dalar BM. Effect of honey and aloe vera extraction on ibuprofen induced liver damage in rats. Journal of Pharmacy and Biological Science. 2012;3:2278- 3008.
Chung YH, Kim JA, Song BC, Koh MS, Lee HS, Yu E, Lee YS, Su DJ. Centrilobular hepatic necrosis, isocitrate dehydrogenase as a marker of centrilobular model of rats. Journal of Gastroenterology and Hepatology. 2001; 16: 328-332.
Oliveira FA, Chaves MH, Almeida FRC, Lima RCP, Silva RM, Maia JL, Brito GA, Santos FA, Rao VS. Protective effect of a- and b- amyrin, a triterpene mixture from protium heptaphyllum (Aubl.) Trunk wood resin against acetaminophen-induced liver injury in mice. Journal of Ethnopharmacology. 2005;98:103- 108.
Eroschenko VP. Atlas of histology with functional correlations (9th edition), Lippincott, Williams and Wilkins publishers; 2000.