title: Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.
abstract: The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure.
authors.affiliation: Department of Biotechnology, College of Science, Taif University, Saudi Arabia Department of Histology, College of Veterinary Medicine, University of Sadat City, Egypt dr_alkafafy@yahoo.com.
authors.forename: Mohamed El-Sayed
authors.initials: Mel-S
authors.lastname: Alkafafy
authors.affiliation: Department of Physiology, College of Veterinary Medicine, Kaferelsheikh University, Egypt Department of Physiology, College of Medicine, Taif University, Saudi Arabia.
authors.forename: Zein Shaban
authors.initials: ZS
authors.lastname: Ibrahim
authors.affiliation: Department of Biotechnology, College of Science, Taif University, Saudi Arabia Department of Biochemistry, College of Veterinary Medicine, University of Sadat City, Egypt.
authors.forename: Mohamed Mohamed
authors.initials: MM
authors.lastname: Ahmed
authors.affiliation: Department of Biotechnology, College of Science, Taif University, Saudi Arabia Department of Biochemistry, College of Veterinary Medicine, Kaferelsheikh University, Egypt.
authors.forename: Samir Ahmed
authors.initials: SA
authors.lastname: El-Shazly
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001218:Aspartame / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012439:Saccharin / Q000494:pharmacology*; D013549:Sweetening Agents / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013549:Sweetening Agents; D012439:Saccharin; D001218:Aspartame
keywords: P27; aspartame; h-Ras; histology; liver; rat; saccharin