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Abstract Sucralose and saccharin-cyclamate mixture are considered safe commercial artificial sweeteners with many health authorities instead of natural sugar. We aimed to reveal their effects on the physiological, immunological and histological profiles in vivo. Mice were given sucralose (0.3 mg/ml) or saccharin-cyclamate mixture (20 mg/ml) in drinking water for 8 and 16 weeks. Only sucralose caused a temporary significant increase in blood glucose after 8 weeks that ended after 16 week. Hematological studies showed that WBCs count was decreased significantly at 16 weeks of sucralose administration (long-term effect). Liver and kidney functionalities showed that AST, ALT, urea and creatinine recorded an increase at 8 and 16 weeks of two artificial sweeteners intake. For Immunological parameters both artificial sweeteners induced a significant increase in IL-6, TNF-Ü and LPS levels with a progress from 8th to 16th weeks post administration. Histological sections showed that both sugars, especially sucralose, caused a severe damage in kidney, liver, pancreas and urinary bladder. Data indicated the adverse effect of both sweeteners. Artificial sweeteners as sucralose, saccharine and cyclamate should be avoided. Their consumption can cause a severe inflammation in liver, kidney, pancrease and urinary bladder.These artificial sweeteners pass across alimentary canal without being digested and change microbiota composition and function. Moreover, they are disturbing intestinal barriers leading to an increase in circulating LPS and pro-inflammatory cytokine secretions |