Oral Acute & Sub-Chronic Toxicity Assessment of Ethanol Leaf Extract of Simarouba glauca

Main Article Content

Sammydavies E. Osagie-Eweka
Noghayin E. J. Orhue
Eric K. I. Omogbai
Fabian O. Amaechina

Abstract

Traditional herbal medicine and their preparations have been widely used for thousands of years and are still in use in developing and developed countries owing to their medicinal values and their presumed relative safety. This belief that medicinal plants are not toxic or are with less side effect due to their natural origin is debatable; hence this study was conducted to evaluate the safety and (or) toxicity of Ethanol leaf extract of Simarouba glauca (EESG) on liver, kidney and heart functions of Wistar rats. The oral acute toxicity of EESG was evaluated in line with Lorke’s method. The sub-chronic toxicity of EESG was carried out according to the OECD guidelines with modification and using a total of twenty-four (24) male Wistar rats; divided into four groups of six rats each, following a two-week acclimatization. Test rats were orally administered EESG at doses of 500, 1000 and 2000 mg/kg body weight respectively daily for thirty (30) days, while the control was given only feed and water ad libitum. At the end of the experiment, the rats were fasted overnight and sacrificed under chloroform anesthesia; relevant biochemical and histopathology analyses were carried out. The data obtained from the oral acute test indicate that the LD50 was above 5000 mg/kg and there was no death recorded. There were significant increases (P ˂ 0.05) in percentage (%) body weight of rats administered respective doses of EESG. There were significant reductions (P˂0.05) in mean liver: body weight ratio of rats administered EESG 500 and 2000 mg/kg respectively, significant reductions (P˂0.05) in mean kidney: body weight ratios of rats given EESG 1000 and 2000 mg/kg respectively; significant reductions (P˂0.05) in mean heart: body weight ratios of test rats administered EESG 2000 mg/kg; whereas others were not significantly different (P˃0.05) relative to their respective control. Plasma ALT and GGT activities of rats administered respective dose of EESG were significantly reduced (P˂0.05); plasma ALP activities were significantly elevated (P˂0.05) relative to the control after 30 days. There were no significant differences (P˃0.05) in plasma total proteins and albumin levels. Plasma total and unconjugated bilirubin of rats administered respective dose of EESG were not significantly different (P˃0.05); whereas, rats given EESG recorded significant reduction in plasma conjugated bilirubin. Plasma urea was significantly elevated (P˂0.05) in rats administered EESG 1000 and 2000 mg/kg respectively. Test rats given EESG 500 and 1000 mg/kg respectively recorded significant elevations in plasma creatinine and rats given EESG 2000 mg/kg recorded significant decrease in plasma creatinine levels; others were not significantly different relative to the control. Plasma chloride and potassium ion levels of rats administered respective doses of EESG were not significantly different (P˃0.05); significant reduction (P˂0.05) in plasma sodium ions concentration in all group compared to the control. Plasma calcium ion levels in all group were not significantly different (P˃0.05); whereas there were significant reductions (P˂0.05) in plasma bicarbonate ion levels relative to their respective controls. Although plasma ALP activity were significantly elevated, there were no elevations in specific liver function enzymes and no visible hepatocellular damage. Furthermore, the conspicuous elevations observed in plasma urea and creatinine levels do not exclusively indicate EESG-induced organ injury. Therefore, it is suggestive that EESG was not significantly toxic to the to the liver, kidney and heart respectively and may be administered at lower doses in further studies.

Keywords:
Leaf extract, toxicity, Simarouba glauca.

Article Details

How to Cite
Osagie-Eweka, S. E., Orhue, N. E. J., Omogbai, E. K. I., & Amaechina, F. O. (2020). Oral Acute & Sub-Chronic Toxicity Assessment of Ethanol Leaf Extract of Simarouba glauca. International Journal of Biochemistry Research & Review, 29(8), 81-100. https://doi.org/10.9734/ijbcrr/2020/v29i830215
Section
Original Research Article

References

World Health Organization (W.H.O) Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines Manila; 1993.

Tilburt JC, Kaptchuk TJ. Herbal Medicine Research and Global Health: An Ethical Analysis Bulletin of the World Health Organization, 2008;86:594-599.

Kamboj A. Drug Evaluation In: Analytical Evaluation of Herbal Drugs Chandigarh College of Pharmacy, Landran, Mohali India. 2012;27-28.

Balunasa MJ, Kinghorn AD. Drug Discovery from Medicinal Plants. Journal of Life Sciences. 2005;78:431-441.

Butler MS. The Role of Natural Product Chemistry in Drug Discovery. Journal of Natural Product. 2004;67:2141-2153.

Pal S, Shukla Y. Herbal Medicine: Current Status and the Future. Asian Pacific Journal of Cancer Prevention. 2003;4:281-288.

Lazarou J, Pomeranz BH, Corey PN. Incidence of Adverse Drug Reaction in Hospitalized Patients: A Meta-analysis of Prospective Studies. Journal of American Medical Association. 1998;279(15):1200-1205.

George P. Concerns Regarding the Safety and Toxicity of Medicinal Plants: An Overview. Journal of Applied Pharmaceutical Science. 2011;1(06):40-44.

Rowin J, Lewis SL. Spontaneous Bilateral Subdural Hematomas Associated with Chronic Ginkgo Biloba Ingestion. Journal of Neurology. 1996;46:1775-1776.

Becker BN, Greene J, Evanson J, Chidsey G, Stone WJ. Ginseng-Induced Diuretic Resistance. Journal of American Medical Association. 1996;276(8):606-607.

Patil MS, Gaikwad DK. A Critical Review on Medicinally Important Oil Yielding Plant Laxmitaru (Simarouba glauca DC). Journal of Pharmaceutical Sciences and Research. 2011;3(4):1195-1213.

ICRAF Agroforestry Tree Database; 2016.
http://ecocrop.fao.org/ecocrop/srv/en/cropView?id=9785.

Taylor L. Simarouba glauca In: Herbal Secrets of Rainforest Sage Press Inc. (2nd edition). 2003;48-58.

Awate PD, Patil MS, Gaikwad DK. Alleviation of Oxidative Damage by Exogenous Application of Plant Growth Regulators on Medicinally Important Oil Yielding Plant Simarouba glauca DC. Under Water Stress Conditions. Indian Journal of Applied Research. 2014;4(6):36-37.

Joshi S, Joshi S. Oil Tree- Laxmitaru glauca University of Agricultural sciences, Bangalore and Indian Council of Agricultural Research, New Delhi, India. 2002;86.

U.S Patent #5676948A on use of Simarouba Extract for Reducing Patchy Skin Pigmentation; 1997.

Bonte F, Grieco PM, Ogura M. Use of a Simarouba Extract for Reducing Patchy Skin Pigmentation. U.S. Patent #5,676,948A; 1997.

Govindaraju K, Darukeshwara J, Srivastava AK. Studies on Protein Characteristics and Toxic Constituents of Simarouba glauca Oilseed Meal. Food and Chemical Toxicology. 2009;47:1327- 1332.

Technical Data Report for Simarouba (Simarouba amara) Sage Press, Inc; 2002.

Ogura M, Cordell, GA, Kinghorn AD, Farnsworth NR. “Potential Anticancer Agents VI. Constituents of Ailanthus excelsa (Simaroubaceae)”. Lloydia. 1977;40(6):579-584.

Valeriote FA, Corbett TH, Grieco PA, Moher ED, Collins JL, Fleck TJ. Anticancer Activity of Glaucarubinone Analogues. Journal of Oncology Research. 1998;10:201-208.

Ghosh PC, Larrahondo JE, Lequesne PW, Raffaul RL. “Antitumor Plants. IV. Constituents of Simarouba versicolor”. Lloydia Journal. 1977;40(4):364-369.

Polonsky J, Varon Z, Jacquemin H, Pettit GR. “The Isolation and Structure of 13,18-dehydroglaucarubinone a New Antineoplastic Quassinoid from Simarouba amara”. Journal of Experientia. 1978;34(9):1122-1123.

Kaij-a-Kamb M., Amoros M, Gierre L. The Chemistry and Biological Activity of Genus centaurea. Pharmaceutica Acta Helvetiae. 1992;6(7):178-188.

Shepheard S. “Persistent Carriers of Entameba histolytica.” Lancet. 1918;1:501.

Cuckler AC, Collins AC, Martins S. Efficacy and Toxicity of Simaroubidin in Experimental Amoebiasis. Journal of Federation Proceedings. 1944;8:284-289.

Wright CW, O’Neill MJ, Phillipson JD, Wrhurst DC. Use of Microdilution to Assess in vitro Antiamoebic Activities of Brucea javanica fruits, Simarouba amara Stem, and a Number of Quassinoids. Journal of Antimicrobial Agents and Chemotherapy. 1988;32(11):1725-1729.

Caceres A, Cano O, Samayoa B, Aguilar L. Plants used in Guatemala for the Treatment of Gastrointestinal Disorders: Screening of 84 Plants against Enterobacteria. Journal of Ethnopharmacology. 1990;30(1):55-73.

Spencer CF, Koniuszy FR, Rogers EF. Survey of Plants for Antimalarial Activity. Lloydia. 1947;10:145-174.

O’Neill MJ, Bray DH, Boardman P, Wright CW, Phillipson JD, Warhurst DC, Gupta MP, Solis P. “Plants as Sources of Antimalarial Drugs, Part 6: Activities of Simarouba amara fruits.” Journal of Ethnopharmacology. 1988;22(2):183-190.

Franssen FFJ, Smeijster LJJW, Berger IMA. In vivo and in vitro Antiplasmodial Activities of Some Plants Traditionally used in Guatemala against Malaria. Journal of Antimicrobial Agents and chemotherapy. 1997;41(7):1500-1503.

Wright CW, Anderson MM, Allen D, Phillipson JD, Kirby GC, Warhurst DC, Chang HR. “Quassinoids Exhibit Greater Selectivity Against Plasmodium falciparum than Against Entamoeba histolytica, Giardia intestinalis or Toxoplasma gondii in vitro.” Journal of Eukaryotic Microbiology. 1993;40(3):244-246.

Grieco PA, Polonsky J, Varn Z. “Therapeutic Quassinoid Preparations with Antineoplastic, Antiviral and Herbistatic Activity” U.S. Patent #6,573,296; 2003.

Osagie-Eweka SDE, Orhue NEJ, Ekhaguosa DO. Comparative Phytochemical Analyses and in-vitro Antioxidant Activity of Aqueous and Ethanol Extracts of Simarouba glauca (Paradise Tree). European Journal of Medicinal Plants. 2016;13(3):1-11.

Lorke DD. A New Approach to Tropical Acute Toxicity Testing. Archives of Toxicology. 1983;53:275-287.

Organisation for Economic Co-operation and Development. Guidance Document on Acute Oral Toxicity Testing OECD Environment, Health and Safety Publications, Series on Testing and Assessment 29 (Online); 2008.

Available:https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd-gd129.pdf.

Rout PK, Rao YR, Jena KS, Sahoo D, Ali S. Safety Evaluation of Simarouba glauca Seed Fat. Journal of Food Science Technology. 2014;51(7):1349-1355.

Oliveira MS, Fernandes MZLCM, Mineiro ALBB, Santos RFD, Viana GEN, Coelho JM, Ribeiro SM, Cunha APGP, Costa JF, Fernandes JF. Toxicity Effects of Ethanol Extract of Simarouba versicolor on Reproductive Parameters in Female Wistar rats. African Journal of Biotechnology. 2016;15(8):221-235.

Reitman S, Frankel S. A Colorimetric Method for the Determination of Serum Glutamic Oxalacetic and Glutamic Pyruvic Transaminases. American Journal of Clinical Pathology. 1957;28(1):56-63.

Englehardt A. Measurement of Alkaline Phosphatase. Aerzti Labor. 1970;16:42.

Teitz NW. Fundamentals of Clinical Chemistry Philadelphia. W B Saunders (3rd edition) 1987;391.

Jendrassik L, Grof P. Vereinfache, Photometrische Methoden. Zur Bestimmung des Blutbilirubins Biochemistry. 1938;297:81-89.

Busher JT. Serum Albumin and Globulin In: Clinical Methods: The History, Physical, and Laboratory Examinations Walker, Hall and Hurst, Boston: Butterworths, third ed. 1990;401-465.

Weatherburn MW. Urease-Berthelot Colorimetric Method. Journal of Analytical Chemistry. 1967;39:971.

Bartels H, Bohmer M. Colorimetric method of Creatinine Determination. Journal of Clinical Chemistry Acta. 1972;37:193.

Ray-Sarker BC, Chauhan UPS. A New Method for Determining Micro Quantity of Calcium in Biological Materials. Analytical Biochemistry. 1967;20:155-166.

Maruna RFL. Colorimetric Determination of Sodium in Human Serum and Plasma. Clinical Chemistry Acta. 1958;2:581.

Trinder P. Colorimetric Determination of Sodium in Human Serum and Plasma. Analyst. 1951;76:596.

Tietz N.W. Fundamentals of Clinical Chemistry, In: Saunders, W.B. Philadelphia, PA, third ed. 1976;897.

Terri AE, Sesin PG. Determination of Serum Potassium by Sodium Tetraphenyboron Method. American Journal of Clinical Pathology. 1958;29:86.

Tietz NW, Pruden EL, Siggaard- Andersen O. Electrolytes, Blood Gas and Acid Base-Balance In: W.B. Saunders. Clinical Chemistry, Philadelphia. 1986;1188.

Gurr E. Methods for Analytical Histology and Histochemistry. Leonard Hill Publishers, first ed. 1959;256.

Windsor L. Tissue Processing In: Laboratory Histopathology, In: Wood, E. A Complete Reference. Churchill Livingstone, New York. 1994;(1):1-42.

Bako HY, Ibrahim M, Mohammad JS, Zubairu M, Bulus T. Toxicity Studies of Aqueous, Methanolic and Hexane Leaf Extracts of Guiera senegalensis in Rats. International Journal of Scientific & Engineering Research. 2014;5(10):1338-1347.

Saidu Y, Nwachukwu FC, Bilbis LS, Faruk UZ, Abbas AY. Toxicity Studies of the Crude Aqueous Extract of Albizzia chevalieri Harms in Albino Rats. Nigerian Journal of Basic and Applied Science. 2010;18(2):308-314.

Petterino C, Argentino-Storino A. Clinical Chemistry and Haematology Historical Data in Controlled Sprague-Dawely Rats from Preclinical Toxicity Studies. Experimental and Toxicological Pathology. 2006;57(3):213-219.

Gurupriya S, Cathrine L, Ramesh J. Qualitative and Quantitative Phytochemical Analysis of Simarouba glauca Leaf Extract. International Journal for Research in Applied Science & Engineering Technology. 2017;5(11):475-479.

Seth SD, Sharma B. Medicinal plants in India. Journal of Medicinal Research. 2004;120:9-11.

Busari MB, Muhammad HL, Ogbadoyi EO, Kabiru AY, Sani S. In Vivo Evaluation of Antidiabetic Properties of Seed Oil of Moringa oleifera Limn. Journal of Applied and Life Sciences International. 2015;2(4):160-174.

Orhue NEJ, Nwanze EAC. Effect of Scoparia dulcis on Trypanosoma brucei Induced Alterations in Serum Transaminases, Alkaline Phosphatase and Bilirubin in Rabbits. Journal of Medical Sciences. 2004;4(3):194-197.

Alkali YI, Jimoh AO, Muhammad U. Acute and Sub-Chronic Toxicity Studies of Methanol Leaf Extract of Cassia singueana F. (Frensen) in Wistar Rats. Journal of Herbal Medicine. 2018;4:2-6.

Ogbonnia SO, Mbaka GO, Nwozor AM, Igbokwe HN, Usman A, Odusanya PA. Evaluation of Micro¬bial Purity and Acute and Sub-Acute Toxicities of a Nigerian Commercial Polyherbal Formulation used in the Treatment of Diabetes Mellitus. British Journal of Pharmaceutical Research. 2013;3(4):948-962.

Wasan K, Najafi S, Wong J, Kwong M. Assessing Plasma Lipid Levels, Body Weight, and Hepatic and Renal Toxicity Following Chronic Oral Administration of a Water Soluble Phytostanol Compound FM-VP4 to Gerbils. Journal of Pharmaceutical Sciences. 2001;4(3):228-234.

Wu AHB. Clinical Chemistry Diagnostic Test In: W.B. Saunders. Tietz Clinical Guide to Laboratory Tests Company, fourth ed. 2006;64-66, 154-156, 470-473, 880-885, 992-993, 234-239, 245, 244-248, 685, 1075, 649, 225, 515, 235, 649, 1097, 317.

European Center for Ecotoxicology and Toxicology of Chemicals, Recognition of, and Differentiation Between, Adverse and Non-Adverse Effects in Toxicology Studies Brussels: European Center for Ecotoxicology and Toxicology of Chemicals. Technical Report No. 85. (Online); 2002.

Available:http://members.ecetoc.org/Documents/Document/TR%20085.pdf (Accessed on 28th September, 2019).

Wolf PL. Clinical Significance of Increased or Decreased Alkaline Phosphatase. Archive of Pathology and Laboratory Medicine. 1978;102:497-501.

McComb RB, Bowers GN, Posen S. Alkaline Phosphatase New York: Plenum Publishing Corporation; 1979.

Tsai LC, Hung MW, Chen YH, Su WC, Chang GG, Chang TC. Expression and Regulation of Alkaline Phosphatases in Human Breast Cancer MCF-7 Cells. European Journal of Biochemistry. 2000;267:1330-1339.

Griffin CA, Smith M, Henthorn PS. Human Placental and Intestinal Alkaline Phosphatase Genes Map to 2q34-q37. American Journal of Human Genetics. 1987;41:1025-1034.

Murali MR, Carey WD. Liver Test Interpretation-Approach to the Patient with Liver Disease: A Guide to Commonly Used Liver Tests. Cleveland Clinic, Cleveland, USA; 2000.

Evans GO. Animal Clinical Chemistry, In: Taylor and Francis. A practical Handbook for Toxicologists and Biomedical Researchers Boca Raton, FL: CRC Press; 2010.

Dobrek L, Baranowska A, Skowron B, Thor P. Biochemical and Histological Evaluation of Kidney Function in Rats after a Single Administration of Cyclophosphamide and Ifosfamide. Journal of Nephrology and Kidney Diseases. 2017;1(1):1002-1008.

Henry RF. Clinical Chemistry Principles and Techniques. In: Harper and Row, Hagerstein, second ed; 1974.

Burtis CA, Ashwood ER. Bicarbonate In: W.B. Saunders. Tietz Fundamentals of Clinical Chemistry. Philadelphia, fifth ed. 2006;166-167.

Alan H, Gowenlock M, Janet R, McMurray S, McLanchlan DM. Varley’s Practical Clinical Biochemistry, sixth ed. 2002;601.