Faculty of Science

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Browsing Faculty of Science by Subject "Acute toxicity"

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    Acute and sub-acute toxicity assessment of methanolic stem bark extract of Khaya anthotheca (Meliaceae) in Wistar rats
    (Springer Nature, 2025-08-29) Akwongo, Betty; Kakudidi, Esezah K.; Nsubuga, Anthony M.; Andama, Morgan; Namaganda, Mary; Tugume, Patience; Asiimwe, Savina; Anywar, Godwin; Katuura, Esther
    Background: Khaya anthotheca (Meliaceae) is a medicinal plant with a wide range of therapeutic properties attributable mainly to the diverse limonoids it contains. Different parts of the plant are used in traditional health care for treatment of various diseases including candidiasis. However, inadequate information on its safety prompted this particular study. Methods: Acute toxicity was assessed according to OECD guidelines 425 in female rats administered with single oral doses of 2000 and 5000 mg/kg body weight (b.wt), and monitored for 14 days for any sign of toxicity and mortality. Sub-acute toxicity was evaluated in both male and female rats following OECD guideline 407, and were administered with extract doses of 500, 250 and 125 mg/kg b.wt repeatedly for 28 days. Body weights were measured weekly, while food and water intake were measured daily. Blood for biochemistry, hematology, and organs for histopathology were collected at the end of the experimental period. Data were analyzed using one-way ANOVA followed by Turkey’s post hoc tests, and repeated measures ANOVA. Results: Acute toxicity showed no mortality, with half-lethal dose (LD50) being greater than 5000 mg/kg b.wt. For sub-acute toxicity, both male and female rats presented significant increase in food and water consumption, increased body weight with increasing time and extract doses (p < 0.05). The 500 mg/kg dosed female rats showed significant increase in stomach weights and alanine aminotransferase (ALT), while renal function marker of chloride ions (Cl−) decreased. Male rats showed dose-dependent significant rise in albumin (ALB) (p = 0.024). For both male and female rats, prolonged use of high extract doses of 250 and 500 mg/kg b.wt for 28 days were toxic to the stomach and liver. Conclusions: The methanolic stem bark extract of K. anthotheca is practically non-toxic at acute dose of 5000 mg/kg b.wt, and safe for clinical use at low sub-acute doses of 125 mg/kg b.wt. However, long-term administration of high extract doses above 125 mg/kg was toxic to mainly the liver and stomach. Thus, long-term administration of high dosage of methanol stem bark extract of K. anthotheca, and phytomedicine development should be done with cautions of potential side effects.
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    Antimycobacterial activity, acute toxicity, and characterisation of compounds from selected medicinal plants used in the treatment of Tuberculosis in Uganda
    (Natural Product Research Network for East and Central Africa (NAPRECA), 2021-11-25) Oloya, Benson; Namukobe, Jane; Heydenreich, Matthias; Ssengooba, Willy; Afayoa, Mathias; Schmidt, Bernd; Byamukama, Robert
    Tuberculosis (TB) is one of the leading causes of death globally, and the rise in drug-resistant forms of TB has become a significant threat (WHO, 2020). Subsequently, it is crucial to explore new, effective and safe anti-TB agents. Several plant species are used in traditional medicine for the treatment of TB in Africa. In Uganda, Acacia hockii, Albizia coriaria, Combretum molle, Warburgia ugandensis, and Zanthoxylum leprieurii are among the plant species used locally to treat tuberculosis, and they could have antimycobacterial compounds that may justify their traditional use but without scientific validation of their bioactivity and toxicity (Anywar et al., 2020; Bunalema et al., 2014; Muthee et al., 2011; Tabuti et al., 2010). This study aimed to conduct antimycobacterial activity and acute toxicity of the selected plant species’ crude extracts and isolate compounds from the stem bark of Z. leprieurii. The aqueous and methanol/dichloromethane (DCM) (1:1) extracts of each of the selected plant species and the isolated compounds were tested for antimycobacterial activity using microplate alamar blue assay (Lawal et al., 2011). For acute toxicity, a single dose (2000 mg/kg) of the aqueous extracts was orally administered to each adult female Winstar albino rat and then observed for 14 days (Lipnick et al., 1995; OECD, 2008). At the end of the experiment, blood samples were collected for haematological and biochemical analyses, while tissue samples from vital organs were collected for histopathological analysis. Isolation and purification of the compounds from the Z. leprieurii stem bark extract were performed using repeated column chromatography. Structure elucidation of the compounds was carried out using spectroscopic methods and by comparison with literature data. Aqueous extracts showed moderate-weak activity against the susceptible (H37Rv) TB strain and weak activity against the multidrug-resistant (MDR) TB strain. Methanol/DCM extracts showed significant-moderate activity against the susceptible (H37Rv) TB strain and moderate-weak activity against the MDR TB strain. After the acute toxicity tests, one mortality and significant lesions in the examined organs following histopathological analyses were recorded from the A. coriaria treated group. Still, the LD50 of all the extracts was estimated to be above 2000 mg/kg. Lupeol, sesamin, trans-fagaramide, arnottianamide, (S)-marmesinin, and hesperidin were isolated from the chloroform/methanol (1:1) extract of Z. leprieurii stem bark, and trans-Fagaramide showed significant antimycobacterial activity against the susceptible (H37Rv) TB strain (Oloya et al., 2021). A. hockii methanol/DCM extract had significant antimycobacterial activity against the susceptible (H37Rv) TB strain, and the methanol/DCM extracts of all the other selected plants had good antimycobacterial activity. The selected plant extracts except A. coriaria exhibited low acute toxicity levels and could be safe for formulations into herbal products. trans-Fagaramide may present a vital template in pursuit of novel and highly effective TB drugs.
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    Phytochemical screening, antimycobacterial activity and acute toxicity of crude extracts of selected medicinal plant species used locally in the treatment of tuberculosis in Uganda
    (Springer Nature, 2022-02-17) Oloya, Benson; Namukobe, Jane; Ssengooba, Willy; Afayoa, Mathias; Byamukama, Robert
    Background Tuberculosis (TB) is one of the leading causes of death globally, and the rise in drug-resistant forms of TB has become a significant threat. Subsequently, it is crucial to explore new, effective and safe anti-TB agents. This study aimed at conducting phytochemical screening, antimycobacterial activity, and acute toxicity of the selected plant species’ crude extracts to assess their toxicological potentials and efficacies against TB. Methods The aqueous and methanol/dichloromethane (DCM) (1:1) extracts of each selected plant species were subjected to phytochemical screening and antimycobacterial activity using microplate alamar blue assay. For acute toxicity, a single dose (2000 mg/kg) of the aqueous extracts was orally administered to each animal following the Organization for Economic Cooperation and Development (OECD) guidelines No. 425 and then observed for 14 days. The animals were closely observed on the general behavior and clinical signs of toxicity, and body weights were recorded. After the termination of the experiment, hematological, biochemical, and histopathological analyses were performed. Results The extracts contained alkaloids, flavonoids, tannins, saponins, steroids, terpenoids, resins, cardiac glycosides, phenolic compounds, and coumarins. Aqueous extracts showed moderate to weak activity against the susceptible (H37Rv) M. tuberculosis strain and weak activity against the MDR-TB strain with Minimum Inhibitory Concentrations (MIC μg/mL) ranging from 293.0–2344.0 and 1172.0–4688.0, respectively. Methanol/DCM extracts showed significant to moderate activity against the susceptible TB strain and moderate to weak activity against the MDR-TB strain with MIC (μg/mL) ranging from 98.0–586.0 and 293.0–781.0, respectively. One mortality was recorded from the A. coriaria treated group following the acute toxicity tests, but the LD50 of all the extracts was estimated to be above 2000 mg/kg. Histopathological analyses did not show any significant lesions in the examined organs except those from the A. coriaria treated group. Conclusion Phytochemical screening of the extracts revealed the presence of alkaloids, tannins, saponins, flavonoids, steroids, terpenoids, resins, cardiac glycosides, phenolic compounds, and coumarins. All the methanol/DCM extracts of the plant species studied have promising antimycobacterial activity. The selected plant extracts studied exhibited low acute toxicity levels except for A. coriaria and could be safe for formulations into herbal products.