Toxicogenetic Studies of Desplatsia dewevrei using Gene Expression of Blood, Pancreatic, and Intestinal Genes in Wistar rats

Authors Affiliation(s)

  • 1Department of Biological and Chemical Sciences, Faculty of Natural and Applied Sciences, Michael and Cecilia Ibru University, Agbarha-Otor, PMB 100, Ughelli, Delta State, NIGERIA
  • 2Department of Plant Biology and Biotechnology, University of Benin, Benin City, PMB 1154, Edo State, NIGERIA
  • 3Center for Bio-computing and Drug Development, Adekunle Ajasin University, Akungba Akoko, Ondo State, NIGERIA

Can J Biotech, Volume 2Issue 4,  Pages 124-131,  DOI: https://doi.org/10.24870/cjb.2019-000126

Received: Feb 7, 2019; Revised: Mar 19, 2019; Accepted: Apr 16, 2019

Abstract

Background: Toxicity studies are relevant in assessing the side effects of chemical substances before they are incorporated into the process of drug development.
Introduction: Desplatsia dewevrei is a scarce forest species believed by natives to be nutritive and therapeutic, without scientific evidence though. Thus, this study was aimed at investigating the possible toxicity of short- and long-term oral administration of D. dewevrei using Wistar rats.
Methods: 0, 30 100, and 1000 mg/kg of D. dewevrei were daily administered p.o for 3 and 28 days to Wistar rats consisting of four animals (two females, two males) per group. Hemotoxicity and liver function tests were done using automated machines from ERMA Inc. RT-PCR method was used to study the regulation of intestinal glucose transporter 4 (GLUT4), glucose transporter 2 (GLUT2), glucagon-like peptide-1 (GLP-1), pancreatic insulin, KCJN5, and L-type voltage-gated calcium channel genes (CACNAIA).
Results: No morphological or hematological signs of toxicity were observed. Liver function test showed an elevated level of high-density lipoprotein (HDL-C) in the treatment group (100 mg/kg). The lethal dose (LD50) of D. dewevrei extracts were above 1000 mg/kg as no mortality was observed at the highest regimen dose used. Up-regulation of pancreatic insulin and down-regulation of intestinal GLUT-2 suggest that the plant may contain therapeutic constituents.
Conclusion: Short- or long-term administration of D. dewevrei is relatively safe.

References

  1. Adewale, J.O., Oludare, T.O., Olumide, K.I. and Olaposi, I.O. (2018) Evidence for the immune-toxicity of green tea polyphenols: A Computational Study. SAJ Pharm Pharmacol 5: 1-9. Crossref
  2. WHO 2007. The World Health Report: a safer future: global public health security in the 21st century. Geneva. 96P.
  3. Oyesola, T.O., Oyesola, O.A. and Okoye, C.S. (2010) Effects of aqueous extract of Aspilia africana on reproductive functions of female Wistar rats. Pak J Biol Sci 13: 126-131. Crossref
  4. Idu, M. and Timothy, O. (2012) 'Plant extracts and biodiversity testing'. In Biological Techniques and Applications (Okhuoya JA, Okungbowa FI, Shittu HO, Eds). UNIBEN Press, Nigeria, 157-179.
  5. Burkill, H.M. (1985) The useful plants of West Tropical Africa. 2nd Edition. Volume 1, Families A-D. Royal Botanic Gardens, Kew, United Kingdom.
  6. Harris, D.J., Moutsamboté, J.M., Kami, E., Florence, J., Bridgewater, S. and Wortley, A.H. (2011) An Introduction to the trees from the North of the Republic of Congo. Royal Botanic Garden Edinburgh.
  7. Ovuakporie-Uvo, O., Idu, M., Obarisiagbon, P. and Abode, C. 2018. Analgesic, pro and anti-inflammatory activities of Desplatsia dewevrei; Cytokine gene expression using Wistar rats and mice. J Phytopharmacol 7: 185-190.
  8. Chen, L., Alam, T., Johnson, J.H., Hughes, S., Newgard, C.B. and Unger, R.H. (1990) Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci USA 87: 4088-4092.
  9. Franca, A, Freitas, A.I., Henriques, A.F. and Cerca, N. (2012) Optimizing a qPCR gene expression quantification assay for S. epidermidis biofilms: a comparison between commercial kits and a customized protocol. PLoS One 7: e37480. Crossref
  10. Omotuyi, I.O., Ovuakporie-Uvo, O. and Idu, M. (2017) Regulation of intestinal GLP-1 and GLUT 2 genes underlie hypoglycemia in Desplatsia subericarpa (Bocq)-fed Wistar rats. J Herbal Drugs 8: 79-86.
  11. Akhila, J.S. Shyamjith, D. and Alwar, M.C. (2007) Acute toxicity studies and determination of median lethal dose. Curr Sci 93:917-920.
  12. Zhu, H., Martin, T.M., Ye, L., Sedykh, A., Young, D.M. and Tropsha, A. (2009) QSAR modeling of rat acute toxicity by oral exposure. Chem Res Toxicol 22: 1913-1921. Crossref
  13. Bhardwaj, S. and Gupta, D. (2012) Study of acute, sub acute and chronic toxicity test. Intl J Adv Res Pharm Bio Sci 2: 103-129.
  14. Raza, M., Al-Shabanah, O.A., El-Hadiyah, T.M. and Al-Majed, A.A. (2002) Effect of prolonged vigabatrin treatment on hematological and biochemical parameters in plasma, liver and kidney of Swiss albino mice. Sci Pharm 70: 135-145.
  15. Teo, S., Stirling, D., Thomas, S., Hoberman, A., Kiorpes, A. and Khetani, V. (2002) A 90-day oral gavage toxicity study of D-methylphenidate and D,L-methylphenidate in Sprague-Dawley rats. Toxicol 179: 183-196. Crossref
  16. Palmer, J.L., Trotter, T., Joy, A.A. and Carlson, L.E. (2008) Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls. J Cancer Surviv 2: 275-282. Crossref
  17. Anonymous (2005) Institute of Medicine, "Dietary intakes and energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acid". National Academy Press. Washington, DC, United States. 380-382.
  18. Ashafa, A.O.T., Yakubu, M.T., Grierson, D.S. and Afolyan, A.J. (2009) Toxicological evaluation of the aqueous extract of Felicia muricata Thunb. leaves in Wistar rats. Afr J Biotech 8: 949-954.
  19. Afolayan, A.J. and Yakubu, M.T. (2009) Effects of Bulbine natalensis Baker stem extract on the functional indices and histology of liver and kidney of male Wistar rats. J Med Food 12: 814-820. Crossref
  20. Yakubu, M.T., Akanji, M.A. and Oladiji, A.T (2005) Aphrodisiac potentials of the aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem in male albino rats. Asian J Androl 7: 399-404. Crossref
  21. Yakubu, M.T., Akanji, M.A. and Oladiji, A.T. (2008) Alteration in serum lipid profile of male rats by oral administration of aqueous extract of Fadogia agrestis stem. Res J Med Plant 2: 66-73. Crossref
  22. Anonymous (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). J Am Medic Assoc 285: 2486-2497. Crossref
  23. Genest, J., Marcil, M., Denis, M. and Yu, L. (1999) High density lipoproteins in health and in disease. J Investig Med 47: 31-42.
  24. Vaziri, N.D. (2006) Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. Am J Physiol - Renal Physiol 290: F262-F272. Crossref
  25. Ovuakporie-Uvo O., Idu M., Eze, G.O. and Ozolua, R.I. (2015) Toxicological studies of Anchomanes difformis Blume (Araceae) using rats and mice. Intl J Basic Clin Pharmacol 4: 1228-1234. Crossref
  26. Rastogi, S.C., Mendiratta, N. and Rastogi, P (2015) Bioinformatics: methods and applications: (Genomics, proteomics and drug discovery). Forth Edition, published by Ghosh, A.K., PHI learning private limited, Rimjhim House, III, Patparganj Industrial Estate, Delhi-110092.;628.