Acute and Delayed Oral Toxicity Studies and Observations on Pregnancy, Gestation and Reproductive Performance of Wistar Rats Administered Limit Dose of Purified Extract from Stem Bark of Antidiabetic Anogeissus leiocarpus (African Birch Tree)

Authors

  • King Akpofure Nelson Esievo Lecturer/Resource Person, College of Veterinary Surgeons, Nigeria, Pathology Faculty, Samaru, Zaria Study Centre, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria. https://orcid.org/0009-0007-7752-0150
  • Lauretta Oghenekevwe Esievo Department of Theriogenology and Production, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.
  • Dahiru Sani Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria. https://orcid.org/0000-0002-0597-5582
  • Kingsley Oghenerukevwe Esievo Department of Agronomy, Faculty of Agriculture, Ahmadu Bello University, Zaria, Nigeria.
  • Edith Monica Esievo Department of Veterinary Surgery, College of Veterinary Medicine, Federal University of Agriculture, Zuru, Nigeria.
  • Emmanuel Oluwadare Balogun Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria. https://orcid.org/0000-0002-2092-0045
  • John Wassagwa Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria.
  • Peter Ibrahim Rekwot Department of Theriogenology and Production, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria. https://orcid.org/0009-0007-7482-3316
  • Lushaikyaa Allam Department of Theriogenology and Production, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria. https://orcid.org/0000-0003-0788-9183
  • Edward Oniovosa Uyobisere Department of Soil Science, Faculty of Agriculture, Ahmadu Bello University, Zaria, Nigeria https://orcid.org/0000-0002-6121-0453

Abstract

Objectives: The maximum purification of the extracts of antidiabetic Anogeissus leiocarpus stem bark led to a quest for its lethal dose (LD50) and effects on pregnancy, gestation, pups (kitten) and reproductive performance of Wistar rats.

Design: Extracts of A. leiocarpus were subjected to column and thin layer chromatography until final purification.

Five (5) each of adult male and female rats were used for the study. The revised limit test dose of 2000mg/kg.bd.wt. was used to evaluate the acute oral toxicity and effects on reproductive characteristics of the purified extracts on Wistar rats. The rats were monitored for instant death and 24hours later, 3 each of male and female rats were humanely sacrificed. On day 0 and 24hours later biomarkers of liver damage, AST, ALT, and ALP and that of kidney, urea, were assayed. The remaining 4 rats (2 males and 2 females) were monitored for additional 14days and thereafter for any effect of the limit dose on reproductive activities.

Results: The limit dose caused no death within the first 24hours and no hepato-renal damages. Pregnancy, gestation, parturition, pups (kitten) and reproductive performance were normal. The median lethal Dose (LD50) is > 2000mg/kg./bd.wt.

Conclusion: Animal experimentation, using Wistar rats showed that purified extracts of A. leiocarpus stem bark as a non-conventional drug for diabetes mellitus, has no effects on pregnancy and reproductive performance. There was no teratogenic effect on pups. The compound has a wide range of safety value.

Keywords: Oral Toxicity, Pregnancy, Gestation, Reproductive Performance, Wistar Rats, Anogeissus leiocarpus, Purified Extract

Keywords:

Oral Toxicity, Pregnancy, Gestation, Reproductive Performance, Wistar Rats, Anogeissus leiocarpus, Purified Extract

DOI

https://doi.org/10.22270/jddt.v13i10.5965

Author Biographies

King Akpofure Nelson Esievo, Lecturer/Resource Person, College of Veterinary Surgeons, Nigeria, Pathology Faculty, Samaru, Zaria Study Centre, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.

Department of Veterinary Pathology, College of Veterinary Medicine, Federal University of Agriculture, Zuru, Nigeria.

Consultant, Research and Diagnosis Unit, Kanesco Global Services Limited (RC 829505), Hayin Mallam, Samaru Zaria, Nigeria.

Lauretta Oghenekevwe Esievo, Department of Theriogenology and Production, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.

Department of Theriogenology, College of Veterinary Medicine, Federal University of Agriculture, Zuru, Nigeria.

Dahiru Sani, Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.

Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.

Kingsley Oghenerukevwe Esievo, Department of Agronomy, Faculty of Agriculture, Ahmadu Bello University, Zaria, Nigeria.

Department of Agronomy, Faculty of Agriculture, Ahmadu Bello University, Zaria, Nigeria.

Edith Monica Esievo, Department of Veterinary Surgery, College of Veterinary Medicine, Federal University of Agriculture, Zuru, Nigeria.

Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, United Kingdom.

Emmanuel Oluwadare Balogun, Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria.

African Centre of Excellence for Neglected Tropical Diseases and Forensic Biotechnology (ACENTDFB), Ahmadu Bello University, Zaria, Nigeria.

John Wassagwa, Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria.

UNESCO International Centre for Biotechnology, University of Nigeria, Nsukka, Nigeria

Peter Ibrahim Rekwot, Department of Theriogenology and Production, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.

  1. Artificial Insemination Unit, National Animal Production Research Institute, Ahmadu Bello University, Shika, Zaria, Nigeria.

Lushaikyaa Allam, Department of Theriogenology and Production, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.

Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria.

Edward Oniovosa Uyobisere, Department of Soil Science, Faculty of Agriculture, Ahmadu Bello University, Zaria, Nigeria

Department of Soil Science, Faculty of Agriculture, Ahmadu Bello University, Zaria, Nigeria

References

Punthakee Z, Goldenberg R, Katz P, Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome, Canadian Journal of Diabetes, 2018; 42:1S10-5. https://doi.org/10.1016/j.jcjd.2017.10.003 PMid:29650080

Qureshi M, Gammoh E, Shakil J, Robbins R, Update on management of type 2 diabetes for cardiologists, Methodist DeBakey Cardiovascular Journal, 2018; 14(4): 273-280. https://doi.org/10.14797/mdcj-14-4-273 PMid:30788013 PMCid:PMC6369620

Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE, Global estimates of diabetes prevalence for 2013 and projections for 2035, Diabetes Research and Clinical Practice, 2014; 103(2):137-49. https://doi.org/10.1016/j.diabres.2013.11.002 PMid:24630390

Amjad S, Jafri A, Sharma AK, Serajuddin M. A, novel strategy of nanotized herbal drugs and their delivery in the treatment of diabetes: Present status and future prospects, Journal of Herbal Medicine, 2019; 17:100279. https://doi.org/10.1016/j.hermed.2019.100279

World Health Organization, Global report on diabetes: executive summary, World Health Organization; 2016.

International Diabetes Federation, IDF Diabetes Atlas.8th ed. 2017.

Armstrong DG, Boulton AJ, Bus SA, Diabetic foot ulcers and their recurrence, New England Journal of Medicine, 2017; 376(24):2367-75. https://doi.org/10.1056/NEJMra1615439 PMid:28614678

Skrepnek GH, Mills Sr JL, Lavery LA, Armstrong DG, Health care service and outcomes among an estimated 6.7 million ambulatory care diabetic foot cases in the US, Diabetes Care, 2017; 40(7):936-42. https://doi.org/10.2337/dc16-2189 PMid:28495903

Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, Qin R, Wang H, Shen Y, Du K, Zhao L, Diabetes is a risk factor for the progression and prognosis of COVID‐19. Diabetes/Metabolism Research and Reviews, 2020; 36(7):e3319. https://doi.org/10.1002/dmrr.3319 PMid:32233013 PMCid:PMC7228407

Hussain A, Bhowmik B, do Vale Moreira NC, COVID-19 and diabetes: Knowledge in progress. Diabetes Research and Clinical Practice, 2020; 162:108142. https://doi.org/10.1016/j.diabres.2020.108142 PMid:32278764 PMCid:PMC7144611

Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H, Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes, Cell Metabolism, 2020; 31(6):1068-77. https://doi.org/10.1016/j.cmet.2020.04.021 PMid:32369736 PMCid:PMC7252168

Kumar V, Ahmed D, Gupta PS, Anwar F, Mujeeb M, Anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of Melastoma malabathricum Linn. leaves in streptozotocin induced diabetic rats, BMC Complementary and Alternative Medicine, 2013; 13(1):1-9. https://doi.org/10.1186/1472-6882-13-222 PMid:24010894 PMCid:PMC3847142

Vega GL, Grundy SM, Current trends in non-HDL cholesterol and LDL cholesterol levels in adults with atherosclerotic cardiovascular disease, Journal of Clinical Lipidology. 2019; 13(4):563-7. https://doi.org/10.1016/j.jacl.2019.05.012 PMid:31248654

Ponnanikajamideen M, Rajeshkumar S, Vanaja M, Annadurai G, In vivo type 2 diabetes and wound-healing effects of antioxidant gold nanoparticles synthesized using the insulin plant Chamaecostus cuspidatus in albino rats, Canadian Journal of Diabetes, 2019; 43(2):82-9. https://doi.org/10.1016/j.jcjd.2018.05.006 PMid:30413371

Blakytny R, Jude E, The molecular biology of chronic wounds and delayed healing in diabetes, Diabetic Medicine, 2006; 23(6):594-608. https://doi.org/10.1111/j.1464-5491.2006.01773.x PMid:16759300

Ihedioha JI, Enahoro G, Prevalence of diabetes mellitus and reference values for the fasting blood glucose levels of locally available breeds of dogs in Warri, Nigeria, Comparative Clinical Pathology, 2019; 28:1107-12. https://doi.org/10.1007/s00580-019-02938-7

Num-Adom SM, Adamu S, Aluwong T, Ogbuagu NE, Umar IA, Esievo KA, Ethanolic extract of Anogeissus leiocarpus ameliorates hyperglycaemia, hepato-renal damage, deranged electrolytes and acid-base balance in alloxan-induced diabetes in dogs, Scientific African, 2022; 16:e01183. https://doi.org/10.1016/j.sciaf.2022.e01183

Meier H, Diabetes Mellitus in Animals: A Review, Diabetes, 1960; 9(6):485-9. https://doi.org/10.2337/diab.9.6.485

Jayalakshmi K, Selvaraj P, Veeraselvam M, Yogeshpriya S, Venkatesan M, Diabetic ketoacidosis in a buck: a case report, Iranian Journal of Veterinary Research, 2019; 20(3):213.

Sharma GU, Diabetes mellitus in a buffalo-cow, Indian Veterinary Journal, 1941; 17:370.

Hui H, Zhao X, Perfetti R, Structure and function studies of glucagon‐like peptide‐1 (GLP‐1): the designing of a novel pharmacological agent for the treatment of diabetes, Diabetes/Metabolism Research and Reviews, 2005; 21(4):313-31. https://doi.org/10.1002/dmrr.553 PMid:15852457

Raj RR, Sahay SS, Tripathi JT, Medications of diabetes mellitus and antidiabetic medicinal plants: a review. International Journal of Indigenous Herbs and Drugs, 2016; 31:19-28.

Balogh E, Toth M, Bölcsházi G, Abonyi-Toth ZS, Kocsis E, Semjen G, Oral hypoglycaemic drugs in alloxan-induced diabetes mellitus in dogs, Acta Veterinaria Brno, 2008; 77(3):363-71. https://doi.org/10.2754/avb200877030363

Rao MU, Sreenivasulu M, Chengaiah B, Reddy KJ, Chetty CM, Herbal medicines for diabetes mellitus: a review. International Journal of Pharmaceutical Technology Research, 2010; 2(3):1883-92.

Gaikwad S, Krishna Mohan G, Sandhya Rani M, Phytochemicals for diabetes management, Pharmaceutical Crops, 2014; 5(1). https://doi.org/10.2174/2210290601405010011

Govindappa M, A review on role of plant (s) extracts and its phytochemicals for the management of diabetes, Journal of Diabetes Metabolism, 2015; 6(7):1-38.

Bacanli M, Effects of phytochemicals against diabetes, Advances in Food and Nutrition Research (2019): 1-28. https://doi.org/10.1016/bs.afnr.2019.02.006 PMid:31351526

Mursiti S, Matsjeh S, The Hypoglycemia Effect of Alkaloid Compounds from Oil Free Mahagony Seeds (Swietenia macrophylla, King), European Journal of Medicinal Plants, 2016; 16(4):1-5. https://doi.org/10.9734/EJMP/2016/18574

Num SM, Oladele SB, Esievo KA, Useh NM, Some observations in Wistar rats administered ethanol extracts of the stem barks of Anogeissus leiocarpus, Asian Journal of Pharmacology and Toxicology, 2014; 2(03):4-10.

Onoja US, Ugwu CC, Uzor PF, Nweze IE, Omeje EO, Nnamani PO, Nwachukwu E, Njoku I, Effiong EJ, Effect of Anogeissus leiocarpus guill and perr leaf on hyperglycaemia and associated dyslipidaemia in alloxan-induced diabetic rats, Dhaka University Journal of Pharmaceutical Sciences, 2018; 17(1):65-72. https://doi.org/10.3329/dujps.v17i1.37120

Motto EA, Lawson-Evi P, Kantati Y, Eklu-Gadegbeku K, Aklikokou K, Gbeassor M, Antihyperglycemic activity of total extract and fractions of Anogeissus leiocarpus, Journal of Drug Delivery and Therapeutics, 2020; 10(3):107-13. https://doi.org/10.22270/jddt.v10i3.4078

Esievo KA, Num-Adom SM, Adamu S, Ogbuagu NE, Aluwong T, Umar IA, Elevated serum sialic acids, a potent biomarker of alloxan-induced type 1 diabetes in dogs by ethanolic extract of Anogeissus leiocarpus, Journal of Diabetes & Metabolic Disorders. 2021; 20:179-86. https://doi.org/10.1007/s40200-021-00726-1 PMid:34178829 PMCid:PMC8212296

Num-Adom SM, Adamu S, Aluwong T, Ogbuagu NE, Umar IA and Esievo KAN, Antidiabetic and antioxidant activities of ethanolic extract of Anogeissus leiocarpus in alloxan induced type 1 diabetes mellitus in Wistar rats, EC Diabetes and Metabilic Research., 2022b; 6.1.

Num-Adom SM, Ogbuagu NE, Aluwong T, Adamu S, Umar IA and Esievo KAN "Dyslipidaemia of alloxan-induced type 1 diabetes in dogs is attenuated by ethanolic extracts of A. leiocarpus stem bark". Diabetes & Obesity International Journal. 7.3: (2022c). https://doi.org/10.23880/doij-16000260

Anefu EO, Ogbuagu NE, Adamu S and Esievo KAN, Healing activities of ethanolic extract of Anogeissus leiocarpus on surgically-induced skin wounds in alloxan-induce diabetic dogs". EC Diabetes Metabolic. Research 2022; 6.3.

Gee GW, Bauder JW, Particle‐size analysis. Methods of soil analysis: Part 1 Physical and mineralogical methods, 1986; 5:383-411. https://doi.org/10.2136/sssabookser5.1.2ed.c15

McLean E O, "Soil pH and lime requirement. In methods of oil analysis". Part 2. Page, A.I., Miller, R.H., Keeny, D.R. (Eds). America Society of Agronomy, Madison, Wisconsin. 1982; 199-224. https://doi.org/10.2134/agronmonogr9.2.2ed.c12

Juo ARS, Selected methods of soils and plant analysis, Institute for Tropical Agriculture. Manual, Series 1. 1979

Bremner JM, Nitrogen‐total. Methods of soil analysis: Part 3 Chemical methods, 1996; 5:1085-121. https://doi.org/10.2136/sssabookser5.3.c37

Udo EJ, Ibia TO, Ogunwale JA, Ano AO, Esu IE, Manual of soil, plant and water analysis. Lagos: Sibon Books Limited, 2009:4-8.

Knudsen D, Peterson GA, Pratt PF, Lithium, sodium, and potassium. Method Soil Analysis, Part. In America Society, 1982.

Anderson JM, Ingram JS, TSBF: A Handbook of Methods of Analysis: CAB International, 1989: 39.

Ebada SS, Edrada RA, Lin W, Proksch P, Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates, Nature Protocols. 2008; 3(12):1820-31.https://doi.org/10.1038/nprot.2008.182 PMid:18989260

Harvey D, Modern analytical chemistry. (1st Ed). McGraw-Hill, 2000; Pp 547-589.

Mbaveng AT, Ngameni B, Kuete V, Simo IK, Ambassa P, Roy R, Bezabih M, Etoa FX, Ngadjui BT, Abegaz BM, Meyer JM, Antimicrobial activity of the crude extracts and five flavonoids from the twigs of Dorstenia barteri (Moraceae), Journal of Ethnopharmacology, 2008; 116(3):483-9. https://doi.org/10.1016/j.jep.2007.12.017 PMid:18280679

Dixon JL, Furukawa S, Ginsberg HN, Oleate stimulates secretion of apolipoprotein B-containing lipoproteins from Hep G2 cells by inhibiting early intracellular degradation of apolipoprotein B, Journal of Biological Chemistry, 1991; 266(8):5080-6. https://doi.org/10.1016/S0021-9258(19)67758-6 PMid:1848237

Ebbo AA, Sani D, Suleiman MM, Ahmad A, Hassan AZ, Acute and sub-chronic toxicity evaluation of the crude methanolic extract of Diospyros mespiliformis hochst ex a. Dc (ebenaceae) and its fractions, Toxicology Reports, 2020; 7:1138-44. https://doi.org/10.1016/j.toxrep.2020.08.028 PMid:32983901 PMCid:PMC7493130

Sani D, Abdu PA, Mamman M, Jolayemi KO, Yusuf PO, Andamin AD, Research Note: Evaluation of acute oral toxicity of povidone-iodine in cockerels using the up-and-down procedure, Poultry Science, 2021; 100(2):631-4. https://doi.org/10.1016/j.psj.2020.11.002 PMid:33518116 PMCid:PMC7858085

Sani D, Sanni S, Ngulde SI, Hypoglycaemic effect of aqueous stem extract of Anisopus mannii in normal rats, African Journal of Pharmacy and Pharmacology, 2009; 3(10):481-4.

Esievo KAN, "Veterinary Clinical Pathology", 1st Edit Spectrum Books, Ibadan. United Kingdom Limited, Jersey, Safari Books (Export) 37: pp. 37, 118-112, 149, 157-158.

Federal Ministry of Agriculture and Natural Resources (FMANR). "Literature review on soil fertility investigations in Nigeria" in five volumes, 1990; 280: 20-25.

Gupta A, Behl T, Sehgal A, Sharma S, Singh S, Sharma N, Garg M, Unmasking the therapeutic potential of biomarkers in type-1 diabetes mellitus, Biointerface Research of Applied Chemistry, 2021; 11:13187-201. https://doi.org/10.33263/BRIAC115.1318713201

Adejoh IP, Mark-Maria AU, Ojochegbe AB, Mayowa OJ, Boniface MT, Effect of aqueous leaf extract of Anogeissus leiocarpus against experimental models of pain and pyrexia. International Journal of Advanced Biological and Biomedical Research, 2019; 6(6):181-8.

Namadina MM, Nuhu A, Aliyu BS, Sani A, Aliko AA, Hayatu M, Babura SR, Muhammad MI, Umar A, Anas A. Physicochemical screening and acute toxicity study of Anogeissus leiocarpa stem bark, Dutse Journal of Pure and Applied Science, 2019; 5(1b):32-40.

Published

2023-10-15
Statistics
Abstract Display: 442
PDF Downloads: 430
PDF Downloads: 26

How to Cite

1.
Esievo KAN, Esievo LO, Sani D, Esievo KO, Esievo EM, Balogun EO, et al. Acute and Delayed Oral Toxicity Studies and Observations on Pregnancy, Gestation and Reproductive Performance of Wistar Rats Administered Limit Dose of Purified Extract from Stem Bark of Antidiabetic Anogeissus leiocarpus (African Birch Tree). J. Drug Delivery Ther. [Internet]. 2023 Oct. 15 [cited 2026 Jan. 21];13(10):11-27. Available from: https://jddtonline.info/index.php/jddt/article/view/5965

Issue

Vol. 13 No. 10 (2023): Volume 13, Issue 10, October 2023

Section

Research

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

How to Cite

1.
Esievo KAN, Esievo LO, Sani D, Esievo KO, Esievo EM, Balogun EO, et al. Acute and Delayed Oral Toxicity Studies and Observations on Pregnancy, Gestation and Reproductive Performance of Wistar Rats Administered Limit Dose of Purified Extract from Stem Bark of Antidiabetic Anogeissus leiocarpus (African Birch Tree). J. Drug Delivery Ther. [Internet]. 2023 Oct. 15 [cited 2026 Jan. 21];13(10):11-27. Available from: https://jddtonline.info/index.php/jddt/article/view/5965
Crossref
Scopus
Google Scholar
Europe PMC

Most read articles by the same author(s)