Int. J. Biosci.10( 5), 51-65, May 2017
Dillenia philippinensis (Rolfe) is an endemic plant to the Philippines. Up to date, there are no available data about the toxicity of the fruit extract, anthocyanins and polyphenols from D. philippinensis fruits. Therefore, this study investigated their adverse effects in mice. A total of 63 female ICR mice were administered with sterile water (control), crude fruit extract and various doses of anthocyanin and polyphenol at 300, 630, 1000, 2000, 3000, 4000 and 5000 mg/kg. Toxicological observations were completed for 14 days according to the guidelines set by OECD. The signs of toxicity observed were decreased motor activity, poor startle reaction, excessive micturition, decreased respiratory depth and rate, tail lashing and body tremor. Liver abnormalities such as calcification along the portal tract and focal periportal necrosis in the liver of mice treated with 5000 mg/kg anthocyanin while periportal degenerative change (focal and extensive) manifested by loss of cytoplasmic eosinophilia in mice administered with polyphenol at the same dose level confirm their toxicity. Based on the observed clinical signs and histopathological evaluation, the fruits are safe to eat as raw foods. The single oral dose of anthocyanin and polyphenol at 5000 mg/kg is toxic however, 300 mg/kg dose is recommended for daily intake.
Akanmu M, Iwalewa E, Elujoba A, Adelusola K. 2004. Toxicity potentials of Cassia fistula fruits as laxative with reference to senna. African Journal of Biomedical Research 7, 23-26.
Archivio M, Filesi C, Di Benedetto R, Gargiulo R, Giovannini C, Masella R. 2007. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita43, 348.
Beis R, Ozturk Y, Aydin S, Gurer F. 2005. Pharmacological and toxicological effects of gas plant. Turkish Journal of Pharmaceutical Science (3), 111-124.
Castro-Bernas G, Gonzales R, Castillo-Sevilla R, Ysrael M. 2005. A guidebook to plant screening: phytochemical and biological. University of Santo Tomas Publishing House, Manila, 110-117.
Conway J. 2000. College of Medicine at Illinois: disease at the cellular level. Retrieved on February 1, 2017 from https://www.med.illinois.edu/m2/pathology/TAReviews/DCL.php.
Cotran R, Kumar V, Robbins S. 1994. Pathologic basis of disease. W.B. Saunders, Philadelphia, 833.
Deepa N, Jena B. 2011. Antioxidant fraction from bark of Dillenia indica. International Journal of Food Properties 14, 1152-1159. http://dx.doi.org/10.1080/10942911003592779
Duan X, Jiang Y, Su X, Zhang Z, Shi J. 2007 Antioxidant properties of anthocyanins extracted from litchi (Litchi chinensis Sonn.) fruit pericarp tissues in relation to their role in the pericarp browning. Food Chemistry 101, 1365. http://doi.org/10.1016/j.foodchem.2005.06.057
Dunnick J, Hailey J. 1992. Toxicity and carcinogenicity studies of quercetin, a natural component of foods. Toxicological Sciences 19(3), 423-431. https://doi.org/10.1016/0272-0590(92)90181-G
Environmental Protection Agency. 2012. Label review manual: chapter 7 precautionary statements. Retrieved on February 4, 2017 from http://www.epa.gov/oppfead1/labeling/lrm/chap-07.pdf.
Fehlert C, Kittel B, Morawietz G, Deslex P, Keenan C, Mahrt C, Nolte T, Robinson M, Stuart B, Deschl U. 2003. Revised guides for organ sampling and trimming in rats and mice. Experimental and Toxicologic Pathology 55, 91-106. https://doi.org/10.1078/0940-2993-00311
Fiette L, Slaoui M. 2011. Drug safety evaluation: necropsy and sampling procedures in rodents. Humana Press, Springer, 39-67.
Gatsing D, Nkeugouapi C, Nji-Nkah B, Kuiate J, Tchouanguep F. 2010. Antibacterial activity, bioavailability and acute toxicity evaluation of the leaf extract of Alchornea cordifolia (Euphorbiaceae). International Journal of Pharmacology 6, 173-182. https://doi.org/10.3923/ijp.2010.173.182
Hagiwara A, Hirose M, Takahashi S, Ogawa K, Shirai T, Ito N. 1991. Forestomach and kidney carcinogenicity of caffeic acid in F344 rats and C57BL/6N x C3H/HeN F1 Mice. Cancer Research 51, 5655.
Halliwell B. 2008. Are polyphenols antioxidants or prooxidants? What do we learn from cell culture and in vivo studies? Archives of Biochemistry and Biophysics. 476(2), 107-12. http://doi.org/10.1016/j.abb.2008.01.028
Hu M. 2007. Commentary: bioavailability of flavonoids and polyphenols: call to arms. Molecular Pharmaceutics. 4 (6), 803-806. http://doi.org/10.1021/mp7001363
Institutional Animal Care and Use Committee. 2014. Oral gavage. Retrieved on February 20, 2017 from http://iacuc.ucsf.edu/Policies/awStandardProcedures.asp
Khan A, Aird M, MacDonald S, Sherlock D. 2013. Medscape: porcelain gallbladder. Retrieved on February 10, 2017 from http://emedicine.medscape.com/article/372582-overview.
Klaassen C, Watkins J. 2010. Casarett & Doull’s Essentials of toxicology. Mc Graw Hill Inc., China, p. 15.
Lorenz E. 2006. Toxicity of pesticides. Publications Distribution Center, Pennsylvania State University, 2.
Martin K, Appel C. 2010. Polyphenols as dietary supplements: a double-edged sword. Nutrition and Dietary Supplements 2, 1-12.
McGill Comparative Medicine and Animal Resource Centre. 2016. The laboratory mouse. Retrieved on February 20, 2017 from https://www.mcgill.ca/cmarc/files/cmarc/cmarc_mouse_module_1_handout_revised_2016.06_for_printing_1.pdf
Mennen L, Walker R, Bennetau-Pelissero C, Scalbert A. 2005. Risks and safety of polyphenol consumption. American Journal of Clinical Nutrition 81, 326S-9S.
Morton D. 1997. Development in animal and veterinary sciences: a scheme for the recognition and assessment of adverse effects in animals. Elsevier, Netherlands, p. 235-240.
Muhammad H, Khan S, Akhtar N. 2012. Antioxidant determination of antioxidant activity and total anthocyanin contents of extracts from pulp and peel of Malus domestica. Asian Journal of Chemistry 24, 2829.
National Registration Authority for Agricultural and Veterinary Chemicals. 1997. The NRA review of mevinphos. Retrieved on February 14, 2017 from http://apvma.gov.au/sites/default/files/publication/14591-mevinphos-review-report.pdf.
Nijveldt R, Van Nood E, Van Hoorn D, Boelens P, Van Norren K, Van Leeuwen P. 2001. Flavonoids: a reviewof probable mechanisms of action and potential applications. The American Journal of Clinical Nutrition 74(4), 418-425.
Organization for Economic Co-operation and Development (OECD). 2002. Test No. 423 Acute oral toxicity- acute toxic class method, guidelines for the testing of chemicals. OECD Publishing, Paris, Retrieved on February 22, 2017 from www.oecd.org/chemicalsafety/riskassessment/1948370.pdf.
Patel C, Dadhaniya P, Hingorani L, Soni M. 2008. Safety assessment of pomegranate fruit extract: acute and subchronic toxicity studies. Food and Chemical Toxicology 46 (8), 2728-35. http://doi.org/10.1016/j.fct.2008.04.035
Piskula M, Terao J. 1998. Accumulation of (-)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues. The Journal of Nutrition 128, 1172-1178.
Prior R, Wu X. 2006. Anthocyanins: structural characteristics that results in unique metabolic patterns and biological activities. Free Radical Research 40, 1014-28. http://doi.org/10.1080/10715760600758522
Rawat S, Jugran A, Giri L, Bhatt I, Rawal R. 2011. Assessment of antioxidant properties of fruits of Myrica esculenta: a popular wild edible species in Indian Himalayan Region. Evidence-Based Complementary and Alternative Medicine 2011,1-8. http://doi.org/10.1093/ecam/neq055
Ray S, Bagchi D, Lim P. 2001. Acute and long term safety evaluation of a novel IH636 grape seed proanthocyanidin extract. Research Communication in Molecular Pathology and Pharmacology 109, 165-197.
Rodriguez-Saona L, Wrolstad R. 2001. Extraction, isolation and purification of anthocyanins. Current Protocols in Food Analytical Chemistry F1-1.1- F1.1.11. http://doi.org/10.1002/0471142913.faf0101s00
Schaeffer M. 1993. Excess dietary vitamin B-6 alters startle behavior of rats. Journal Nutrition: Nutrient Requirements and Interactions 123, 1444-1452.
Sergediene E, Jonsson K, Szymusiak H, Tyrakowska B, Rietjens I, Cenas N. 1999. Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: description of quantitative structure-activity relationships. FEBS Letters. 462, 392-6. http://doi.org/10.1016/S0014-5793(99)01561-6
Shendge P, Patil L, Kadam V. 2011. In vitro evaluation of antioxidant activity of Dillenia indica Linn leaf extract. International Journal of Pharmaceutical Sciences and Research2, 1814 – 1818. http://dx.doi.org/10.13040/IJPSR.09758232.2(7).1814-18
Singh T, Mukhopadhayay S, Sar T, Ganguly S. 2012. Acetamiprid induces toxicity in mice under experimental conditions with prominent effect on the hematobiochemical parameters. Journal of Drug Metabolism and Toxicology 3, 134. http://doi.org/10.4172/2157- 7609.1000134
Tan A, Konczak I, Ramzan I, Sze D. 2011. Antioxidant and cytoprotective activities of native Australian fruit polyphenols. Food Research International 44, 2034. http://doi.org/10.1016/j.foodres.2010.10.023
Wattanathorn J, Thukummee W, Thipkaew C, Wannanond P, Tong-un T, Muchimapura S, Kaewrueng W. 2012. Acute and subchronic toxicity of mulberry fruits. American Journal of Agricultural and Biological Sciences 7(3), 378-383. http://doi.org/10.3844/ajabssp.2012.378.383
Weaver J, Briscoe T, Hou M, Goodman C, Kata S, Ross H, McDougall G, Stewart D, Riches A. 2009. Strawberry polyphenols are equally cytotoxic to tumourigenic and normal human breast and prostate cell lines. International Journal Oncology 34(3), 777-786. http://doi.org/10.3892/ijo_00000203
World Conservation Monitoring Centre. 1998. Dillenia philippinensis, The IUCN redlist of threatened species. Retrieved on January 5, 2017 from http://dx.doi.org/10.2305/IUCN.UK.1998.RLTS.T33202A9764984.en.
Yildiz H, Sengul M, Celik F, Hegedus A, Ercisli S, Tosun M. 2010. Some phytochemical and antioxidant characteristics of wild and cultivated blackberry (Rubus caucasicus) fruits. Food, Agriculture and Environment 8, 156.