Effect of Chronic Neotame Exposure on Visfatin Level, Oxidative Stress Biomarkers, and Small Intestine Tissue in Male Rats

Background: Neotame (NEO) is a potent artificial sweetener widely used as a low-calorie sugar substitute. Although considered safe at recommended levels, prolonged exposure may contribute to physiological and biochemical disturbances through oxidative stress and free radical production, potentially resulting in dose- and duration-dependent cellular and functional damage.
Objectives: This study aimed to investigate the effects of chronic neotame administration on oxidative stress biomarkers (GSH and MDA), serum visfatin levels, and histopathological alterations in the small intestine.
Materials and Methods: A total of 40 healthy adult male albino rats (180–230 g, 60–75 days old) were housed in the animal house of the College of Science, University of Babylon. The animals were acclimatized for two weeks under controlled laboratory conditions (20–25°C, 12 h light/dark cycle) with free access to food and water, The experiment began on the first of December, 2025, and ended on the first of March, 2026.
Results: Statistical analysis revealed no significant differences in serum visfatin levels among the experimental groups. In contrast, oxidative stress biomarkers showed significant alterations following chronic neotame administration, with a significant decrease (P ≤ 0.05) in glutathione (GSH) levels and a significant increase (P ≤ 0.01) in malondialdehyde (MDA) levels in a dose-dependent manner, indicating enhanced oxidative stress and lipid peroxidation. Histopathological examination of the small intestine demonstrated dose-related tissue alterations, including goblet cell proliferation, villous atrophy and sloughing, inflammatory cell infiltration, vascular congestion, crypt hyperplasia, villous fusion, and necrosis of intestinal glands, with more severe lesions observed at higher neotame doses.
Conclusion: The study reveals that continuous exposure to neotame leads to dose-dependent physiological, Histopathological, and biochemical alterations.