INTERNATIONAL JOURNAL OF HEALTH AND PHARMACEUTICAL RESEARCH (IJHPR )
E-ISSN 2545-5737
P-ISSN 2695-2165
VOL. 9 NO. 4 2024
DOI: 10.56201/ijhpr.v9.no4.2024.pg16.36
Naomi Akpevwe Mogborukor, Joshua Charles Isirima
This study assessed the impact of Persea americana seed extract on 5-fluorouracil (5-FU) induced cardio-histoxicity and oxidative stress in Wistar rats. 72 animals from a total of 77 were treated intraperitonially with a single dose of 150mg/kg of 5-FU to simulate toxicity in the heart and to cause oxidative stress. These animals were grouped into six (group 2-7). However, animals in group 1 served as control and received only feed and water. Group 2 was labeled negative control, animals in group 3 were administered with 500mg/kg of vitamin C while the animals in groups 4- 6 received 250mg/kg, 500mg/kg and 1000 mg/kg of the extract and those in group 7 received the medium dose of vitamin C in combination with 500mg/kg of the extract. Groups 2-7 had 12 animals and 3 from each group were sacrificed weekly for 4 weeks. The animal’s blood and tissue was collected for biochemical and histological analysis. It was observed that the administration of 5- FU caused cardio-toxicity and oxidative stress which led to some alterations in the histology of the heart and changes in oxidative stress markers like Glutathione, Catalase, Superoxide dismutase and Malondialdehyde. However, treatment with the extract ameliorated the adverse effects associated with the drug via enhancing antioxidant defense, decreasing inflammation and suppressing toxicity to the heart.
5-fluorouracil, Persea americana seed, cardio-histotoxicity, oxidative stress markers
Akinyemi, A.J., Adedayo, O.A., & Ganiyu, O. (2019). Protective effect of avocado pear seed
extract against oxidative stress and cellular damage. Journal of Pharmacy and
Pharmacology, 71(8), 1043-1053.
Al-Asmari, A.K., Al-Zahrani, A.M., Khan, A.Q., Al-Shahrani, H.M., & Ali Al Amri, M. (2016).
Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and
reproductive organ damage in Wistar rats: A biochemical and histological study. Human
Exp Toxicol, 35:10–20.
Araújo, R. G., Rodriguez-Jasso, R. M., Ruiz, H. A., Pintado, M. M. E., & Aguilar, C. N. (2018).
Avocado by-products: Nutritional and functional properties. Trends in Food Science &
Technology, 80, 51-60.
Ayala, A., Muñoz, M.F., & Argüelles,S. (2014). Lipid Peroxidation: Production, Metabolism, and
Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxidative
Medicine and Cellular Longevity, 1–31.
Basselin, C., Fontanges, T., & Descotes, J. (2011). 5-Fluorouracil-induced Takoo-Tsubo-like
Syndrome. Pharmacotherapy, 31, 226.
Bonetti, P.O., Lerman, L.O., & Lerman, A. (2003). Endothelial dysfunction: A marker of
atherosclerotic risk. Arterioscler Thromb Vasc Biol, 23: 168–175.
Carleton, H.M., Drury, R.A.B., & Wallington, E.A. (1967). Carleton’s Histological Technique.
4th ed. London: Oxford University Press; Chapter 3-7, pp.40-129.
Claiborne, A. (1985) Catalase activity. In: Greenwald, R.A., Ed., CRC . Handbook of Methods for
Oxygen Radical Research, CRC Press, Boca Raton, 283-284.
Dabas, D., Elias, R. J., Lambert, J. D., & Ziegler, G. R. (2019). In vitro antioxidant and cancer
inhibitory activity of a colored avocado seed extract. International Journal of Food
Science, 2019, 1-7.
Deponte, M. (2013). Glutathione catalysis and the reaction mechanism of glutathione-dependent
enzymes. Biochimica et Biophysica Acta, 3217–3266.
Droge, W. (2002). Free radicals in the physiological control of cell function. Physiological
Reviews, 82, 47–95.
Gnanadhas, E.N., Lakshminarasaiah, U., Gopas, J., & Nishigaki, I. (2014). Antioxidants and
human diseases. Clinica Chimica Acta, 436, 332–347.
Halliwell, B., & Gutteridge, J.M.C. (2015). Free Radicals in Biology and Medicine, 5th edition, pp
215-227.
Hattori, Y., Nishigori, C., Tanaka, T., Ushida, K. Nikaido, O., Osawa, T., Hiai, H., Imamuru, S.,
& Tyokuni, S. (1997). 8 Hydroxy-2-deoxyguanosine is increased in epidermal cells of
hairless mice after chronic ultraviolet B exposure. J Invest Dermatol, 89, 10405–9.
Hayyan, M., Hashim, M.A., & Anjkut, I.M. (2016). Superoxide Ion: Generation and Chemical
Implications. Chem. Rev, 116 (5), 3029–85.
Heistad, D.D., Armstrong, M.L., Marcus, M.L., Piegors, D.J., & Mark A.L. (1984). Augmented
responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys.
Circ Res, 54: 711–718.
Imafidon, K., & Amaechina, F. (2010). Effects of aqueous seed extract of Persea americana
Mill(avocado) on blood pressure and lipid profile in hypertensive rats. AdvBiol Res, 4(2),
116-121.
Jasvinder, K., Deepak, P., & Vinod, K. (2018). 5-Fluorouracil-induced cardiotoxicity: A review
of the possible mechanisms and clinical implications. Journal of Clinical and Experimental
Cardiology, 9(2), 1-9.
Jensen, S.A., & Sorensen, J.B. (2006). Risk factors and prevention of cardiotoxicity induced by 5-
fluorouracil or capecitabine. Cancer Chemother Pharmacol,58(4):487–493.
Joanna, I. (2016). Aging and Degradation of Printed Materials, Printing on Polymers. Elsevier,
pp. 353–370.
Labianca, R., Beretta, G., Clerici, M., Fraschini, P., & Luporini, G. (1982). Cardiac toxicity of 5-
Fluorouracil. A study in 1083 patients, Tumori, 68:505–10.
Longley, D.B., Harkin, D.P., & Johnston, P.G. (2003). 5-fluorouracil: Mechanisms of action and
clinical strategies. Nat Rev Canc,3:330–338.
Lorke, D.A. (1983). New Approach to Practical Acute Toxicity. Testing. Archives of Toxicology,
54: 275-287.
Mead, R., Curnow, R.N., & Hasted, A.M. (1993). Statistical methods in Agriculture and
Experimental biology, 2.
Misra, H.P., & Fridovich, I. (1972). The role of Superoxide Anion in the autoxidation of
Epinephrine and a Simple Assay for Superoxide Dismutase. Journal of Biological
Chemistry, 247, 3170-3175.
Naomi, A.M., & Joshua, C.I. (2024). Effect of Persea Americana seed extract on 5-Fluorouracil
Induced Hepatic Histotoxicity on Wistar Rats. International Journal of Public Health,
Pharmacy and Pharmacology, 9(3), 50-67.
Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by
thiobarbituric acid reaction. Analytical Biochemistry, 95, 351-358.
Saif, M,W., Shah, M.M., & Shah, A.R. (2009). Fluoropyrimidine-associated cardiotoxicity:
Revisited. Expert Opin Drug Safe 8: 191–202.
Sato, H., Shibata M., Shimizu, T., Shibata, S., Toriumi, H., Ebine, T., Kuroi T., & Iwashita T.
(2013). Differential cellular localization of antioxidant enzymes in the trigeminal ganglion.
Neuroscience, 248, 345–358.
Sedlak, J., & Lindsay, R. H. (1968). Analytical Biochemistry, 25, 1192-1205.
Soledad, C.P.T., Paola, H.C., Carlos, E., Israel, R., GuadalupeVirginia, N.M., & Raúl, Á.S. (2021).
Avocado seeds (Persea americana cv. Criollo sp.): Lipophilic compounds profile and
biological activities. Saudi J. Biol. Sci, 28, 3384–3390.
Taniyama, Y., & Griendling, K.K. (2003). Reactive oxygen species in the vasculature.
Hypertension, 42, 1075–1081.
Thalambedu, N., & Khan, Y. (2019). Fluorouracil (5-FU) induced cardiomyopathy. (2019).
Cureus, 11(7), e5162.
Tremocoldi, M.A., Rosalen, P.L., Franchin, M., Massarioli, A.P., Deny C., Daiuto, E.R., Paschoal,
J.A.R., Melo, P.S,. & de Alencar, S.M.Augusto, J., Massarioli, A.P. (2018). Exploration of
avocado by-products as natural sources of bioactive compounds. PLoS ONE, 13, e0192577.
Tsibiribi, P., Bui-Xuan, C, Bui-Xuan, B., Lombard-Bohas, C., Duperret, S., Belkhiria, M, Tabib,
A., Maujean, G., Descotes, J., Timour, Q. (2006). Cardiac lesions induced by 5-fluorouracil
in the rabbit. Hum Exp Toxicol 25: 305–309.
Tugiyanti, E., Yuwanta, T., Zuprizal, Z., & Rusman, R. (2013). Supplentation of Vitamin E and
C in Feed on meat Quality. Vet World, 12(10):1608 -1615.
Uchenna, U.E., Shori, A,B., & Baba, A.S. (2017). Inclusion of avocado (Persea americana) seeds
in the diet to improve carbohydrate and lipid metabolism in rats. Revista argentina de
endocrinología y metabolismo, 54(3), 140–148.
Unlu, N., Bohn, T., Clinton, S.K. & Schwartz, S.J. (2005) Carotenoid Absorption from Salad and
Salsa by Humans Is Enhanced by the Addition of Avocado or Avocado Oil. The Journal
of Nutrition, 135, 431-436.
Villarreal-Lara, R., Rodríguez-Sánchez, D.G., Díaz De La Garza, R.I., M.I. García-Cruz, M.I.,
Castillo, A., & Pacheco, A. (2019). Purified avocado seed acetogenins: Antimicrobial
spectrum and complete inhibition of Listeria monocytogenes in a refrigerated food matrix.
CyTA-Journal of Food, 17 (1), pp. 228-239.
Woo, R.A., Melure, K.G., & Lee, P.W. (1998). DNA dependent protein kinase acts upstream of
p53 in response to DNA damage. Nature, 394, 700–4.