ACUTE TOXICITY STUDIES OF MAX GLUCAGON LIKE PEPTIDE (MAX GLP-1) ON MALE WISTAR RATS
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Abstract
Glucagon-like peptide-1 (GLP-1) is an incretin hormone with potential therapeutic applications in metabolic disorders, including type 2 diabetes mellitus. While its pharmacological effects have been extensively studied, data on its acute toxicity profile remain limited. This study aimed to evaluate the acute oral toxicity of a MaxGLP-1 supplement in male Wistar rats using the Lorke method. Experimental animals were administered single oral doses of 10, 100, 1000, 1600, 2900, and 5000 mg/kg and monitored continuously for 24 hours and subsequently for 14 days to detect immediate, persistent, or delayed toxic effects. Observations included clinical signs, mortality, feed and water consumption, body weight changes, and external and internal organ examinations, supplemented by histopathological evaluation of the liver and spleen. No mortality occurred at any dose, establishing an LD₅₀ greater than 5000 mg/kg. Immediate effects were mild and transient, including slight restlessness at 1000 mg/kg and mild sedation at higher doses, which resolved within hours. Delayed adverse effects were limited to intermittent mild irritation or itching in animals exposed to doses ≥1000 mg/kg. Feed and water intake, relative weight gain, feed efficiency, and body weight progression were not significantly altered (p>0.05) across all groups. External and internal examinations revealed no gross pathological changes, and histopathological analysis of liver and spleen at 1600 mg/kg showed no lesions. These findings indicate that MaxGLP-1 possesses low acute oral toxicity, with a conservative No Observed Adverse Effect Level (NOAEL) of 100 mg/kg in male Wistar rats. This study provides foundational safety data supporting the further preclinical development of MaxGLP-1 and shows the need for subsequent subacute and chronic toxicity evaluations to establish long-term safety profiles.
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