ACUTE TOXICITY

ACUTE TOXICITY AND IN VIVO ANTIMALARIAL ACTIVITY OF PERSEA AMERICANA (UBE BEKEE) SEED METHANOL EXTRACT IN MICE INFECTED WITH PLASMODIUM BERGHEI NK65

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Abstract
Malaria is an acute, life-threatening parasitic infection caused by protozoan parasites of the genus Plasmodium, posing a significant global health threat. The most virulent form that infects humans is Plasmodium falciparum. Current first-line treatments involve Artemisinin-based combination therapies (ACTs), but the increasing prevalence of antimalarial drug resistance constitutes a major impediment to global malaria control initiatives. Historically, traditional knowledge of indigenous plants has guided the discovery of effective antimalarials, such as quinine and artemisinin, underscoring the urgent need to explore plant-based medicines for alternative therapeutic strategies. Persea americana (avocado), a commercially valuable fruit tree, is used traditionally for malaria treatment. This study aimed to evaluate the methanolic extract of Persea americana seed for its antimalarial activity and acute toxicity level. The overall objective was to scientifically validate the plant’s use for anti-malarial therapy and suggest it as a promising source for new antimalarial compounds. Acute toxicity was assessed in six male Wistar strain mice (6–8 weeks old) using the limit test dose up and down procedure of the Organisation for Economic Cooperation and Development (OECD) guideline 423. Antimalarial activity was tested using the Peter’s 4-day Suppressive test in 20 male Wistar strain mice inoculated intraperitoneally with Chloroquine Sensitive Plasmodium berghei NK65 infected red blood cells. Extract doses of 100, 250, and 500 mg/kg b.wt. were administered orally and daily for four days. Control groups received normal saline vehicle, chloroquine (25 mg/kg b.wt.), or lithium chloride (10 mg/kg b.wt.). In the acute toxicity study (OECD guideline 423), following the administration of 2000 mg/kg b.wt. of the Persea americana seed methanol extract, no mice death was recorded, and no other signs of toxicity were observed during the 14-day period. Therefore, the extract was deemed safe for administration at 2000 mg/kg b.wt.. The findings suggest that the Persea americana seed methanol extract has a low acute toxicity profile, as demonstrated by the safety of administering 2000 mg/kg b.wt. in mice. The antimalarial activity of Persea americana recorded decrease in % Parasitemia in mice and the most significant decrease in the highest dose administered. This validates the traditional use of the plant sample and highlight the Persea americana seed as a promising resource for discovering new antimalarial compounds
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ACUTE TOXICITY, GLUCOSE LEVEL AND ANTIDIABETIC EFFECT OF METHANOL EXTRACT OF Moringa oleifera LEAVES ON STREPTOZOTOCIN- INDUCED DIABETES MELLITUS ON LIVER INTEGRITY IN SPRAGUE-DAWLEY RATS

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This study was conducted to investigate the acute toxicity, blood glucose concentration and the anti-diabetic effect of methanol extract of Moringa oleifera in streptozotocin- induced diabetes mellitus on Liver integrity in Sprague-Dawley rats. Acute toxicity was carried out in two phases using different doses of Moringa oleifera leaves extract. There was no mortality recorded in both phases. A total of twenty-five Sprague-dawley rats divided into five groups of five animals each were used for the experiment. All animals were allowed unlimited access to feed and water. Group 1 served as control and receieved normal feed and water. Animals in groups 2,3,4 & 5 were induced with diabetes mellitus using 55mg/kg body weight streptozotocin. Animals in group 2 were treated with standard drug glibenclamide (5mg/kg bwt) once daily for 21 days. In addition, animals in groups 3,4 &5 were treated with graded doses of Moringa oleifera leaves extract (100mg/kg bwt, 200mg/kg bwt and 300mg/kg bwt) respectively. Blood glucose level was checked weekly for three weeks. On day 22, all the animals were sacrificed and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Malondialdehyde (MDA) were analyzed. Results obtained showed that there was a significant (P<0.05) decrease in ALT and MDA level. Also there was a significant (P<0.05) decrease in AST in 250mg/kg bwt and 300mg/kg bwt. There was a significant increase in AST in groups treated with 100mg/kg bwt and 200mg/kg bwt this maybe as a result of the low doses of the Moringa oleifera leaves extract used in their treatment. 300mg/kg bwt maybe the safest and best dose to use for medicinal purposes. All the animals treated with methanol extract of Moringa oleifera showed a significant (P <0.05) decrease in blood glucose concentration. The animals treated with glibenclamide maintained a significant high blood glucose concentration, there was no reduction in blood glucose concentration in this group when compared with control group after treatment for 21 days. Methanol extract of Moringa oleifera leaves has an anti-diabetic effect and also liver protective effect because of the antioxidant and phytochemical compounds it
contains.
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co-supervisor

ACUTE TOXICITY STUDIES OF CELLIFEIQ IN MALE WISTAR RATS

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Acute toxicity studies is essential for determining the immediate safety of substances following a single high-dose exposure, providing early indicators of potential adverse effects or lethality. CellifeIQ, a multi-component nutraceutical formulated with antioxidant-rich herbal extracts, vitamins, and minerals, is widely promoted for supporting cellular health, yet its toxicological safety has not been scientifically evaluated.This study evaluated the acute oral toxicity of CellifeIQ in male Wistar rats. Using Lorke’s method,male wistar rats received single oral doses of 10, 100, 1000, 1600, 2900, and 5000 mg/kg and were observed for 14 days for mortality, behavioural changes, body-weight trends, feed and water intake, and gross pathological alterations in major organs. No mortality occurred at any tested dose, indicating an LD₅₀ greater than 5000mg/kg. Mild and transient effects, such as slight restlessness or sedation, were observed at higher doses but resolved within hours, while delayed mild itching was noted only at doses ≥1000 mg/kg. Body-weight progression, feed consumption, water intake, and feed efficiency showed no significant differences compared to controls (p>0.05). Gross necropsy revealed no visible abnormalities in the liver, kidneys, heart, lungs, or spleen. CellifeIQ demonstrated very low acute oral toxicity and may be considered practically non-toxic under single-dose exposure conditions in male Wistar rats. However,further studies including sub acute and chronic toxicity,biochemical assays,histopathology, and genotoxicity evaluations are recommended to fully characterize its long-term safety profile.
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co-supervisor

ACUTE TOXICITY AND EFFECT OF Terminalia mantaly H. Perrier (COMBRETACEAE) LEAF EXTRACT ON HAEMATOLOGICAL PARAMETERS OF WISTAR RATS

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The leaf of T. mantaly is a component of traditional medicine, yet its scientific safety profile, particularly on the blood, is not well-established. This research aimed to provide information on the acute toxicity profile and a comprehensive description of the haematological effects of the plant's methanol leaf extract in Wistar rats, by examining both the immediate effect of a single high dose, and the sub – acute effect of repeated daily administrations. The leaf of T. mantaly was collected, authenticated, dried and milled into powder form. The powder (1050 g) was Soxhlet extracted using methanol, concentrated and dried to obtain 27.98% yield of extract. Acute toxicity test was done using Lorke’s method. Evaluation of the acute effect of a single high dose of 5000 mg/kg and the sub – acute effect of graded doses (200, 400 and 800 mg/kg) of the extract on haematological parameters of female Wistar rats, were done using standard methods. The acute toxicity test revealed that the extract is relatively safe with LD50 > 5000 mg/kg. However, administration of the 5000 mg/kg dose of the extract revealed a non – toxic physiological stress response, which manifested as a decrease in platelets (thrombocytopenia) and lymphocytes (lymphopenia), as well as a sharp rise in neutrophils (neutrophilia). The 28 days sub – acute study demonstrated the safety profile associated with the administration of lower graded doses of the extract. An immunomodulatory effect, with a slight increase in the number of lymphocytes an platelets, were observed. In conclusion, the methanol leaf extract of T. mantaly possesses a high margin of safety and it is relatively safe, at the tested doses. However, caution is seriously advised in its use, at high doses.
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