Onah et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):207-216 ISSN: 2250-1177 [207] CODEN (USA): JDDTAO Available online on 15.05.2020 at jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research © 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted non-commercial use, provided the original work is properly cited Open Access Research Article Acute Oral Toxicity Studies of the Crude Extract of Endophytic Fungi Isolated from Annona senegalensis Pers Onah, A. Ikechukwu. 1* , Kenechukwu, C. Franklin 2 , Berebon, P. Dinebari 1 , Agboke, A. Akeem. 3 Ibezim, E. Chinedum. 2 , Attama, A. Anthony. 2 1 Department of Pharmaceutical Microbiology and Biotechnology, University of Nigeria, Nsukka, Nigeria 2 Department of Pharmaceutics, University of Nigeria, Nsukka, Nigeria 3 Department of Pharmaceutics and Pharmaceutical Technology, University of Uyo, Nigeria ABSTRACT Establishment of safety and toxicity profiles of metabolites of endophytic organisms from known medicinal plants are crucial in their pharmacological and biological applications. The aim of this study was to evaluate the oral acute toxicity (LD50) of crude extract of endophytic fungi isolated from Annona senegalensis Pers. The endophytic fungal metabolite was extracted with ethyl acetate. The LD50 was estimated following the method described by Lorke. Three dose levels (10, 100, and 1000 mg/kg) of the crude extract were administered t o three mice each for the first phase using oral gavage needle in a single dose disposable syringe. The animals were observed for possible deaths or other side effects of the test substance in each group within 24 hours of the treatment. In the second phase, which was deduced from the first phase, eight mice were sub-divided into four groups of two mice each and they were treated with doses of 1200, 1600, 2900 and 5000 mg/kg orally. They were also observed within 24 hours and final LD50 value was determined. Results showed that the endophytic fungal extract exhibited no mortality or any histological defect in the liver tissues of the mice. More so, the immunological parameter tested showed significant increase in neutrophils and lymphocytes relative to the control in all the fungal isolates. Additionally, the LD 50 for the crude metabolites was > 5000 mg/kg. This study has revealed that crude extract of endophytic fungi isolated from Annona senegalensis Pers did not show oral acute toxicity in mice. Further studies will evaluate long term-toxicity of the crude extract. Keywords: Endophytes, LD50, Annona senegalensis, Metabolites, Fungi Article Info: Received 11 March 2020; Review Completed 24 April 2020; Accepted 04 May 2020; Available online 15 May 2020 Cite this article as: Onah AI, Kenechukwu CF, Berebon PD, Agboke AA Ibezim EC, Attama A A, Acute Oral Toxicity Studies of the Crude Extract of Endophytic Fungi Isolated from Annona senegalensis Pers, Journal of Drug Delivery and Therapeutics. 2020; 10(3):207- 216 http://dx.doi.org/10.22270/jddt.v10i3.4052 *Address for Correspondence: Onah, A. Ikechukwu, Department of Pharmaceutical Microbiology and Biotechnology, University of Nigeria, Nsukka, Nigeria 1. INTRODUCTION Man has over time relied on plants for food and medicines. [1, 2] The rationale for the use of these plants by man for treatment of different disease conditions has been variously described as traditional, economic, accessibility and effectiveness. [3, 4, 5] Annona senegalensis Pers. is one of the foremost plants used in West Africa with documented evidence of its use traditionally in the treatment of malaria, trypanosomiasis, snake bite, body pain, fever, urinary tract infection, convulsion hepatitis e t c. [6, 7] Some of these plants known for their medicinal values are consistently being consumed for immediate health challenges without recourse to any established safety or scientific protocols. [1, 2] This has however, placed some consumer of these medicinal products at high risks of acute or chronic toxicities. Acute toxicity testing provides baseline toxicological data that can be used to describe an agent or substance based on its possible health risk. [8] It also describes the adverse toxicological effects of an agent that occur either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours) [8, 9]. In undertaking acute toxicity testing, various routes of exposure such as oral, dermal or inhalational are often explored in mice which serve as the most common animal model in toxicity studies. [8, 10] In a related development, the exploration of microbial diversity of medicinal plants as new frontiers in searching for novel compounds against human diseases has attracted interest towards the endophytic research [11]. In past years, endophytic studies were not eliciting so much interest among the scientific community probably due to focus on plant extract exploration. However, owing to recent