Nephrotoxic Impacts of Aspartame and Saccharin in Wistar Rat Model: Biochemical, Molecular and Histopathological Approach

Abstract

The present study was designed to resolve the dispute about the nephrotoxicity of the non-nutritive sweeteners (NNS), mainly aspartame and saccharin.Twenty-five, 7-week old, male Wistar rats were divided into a control group (n=5) and 4 experimental groups (n=5).The first and second experimental groups received daily doses of 250 mg aspartame/ Kg BW (Asp.L) and of 1000 mg aspartame/ Kg BW (Asp.H), respectively.The third and fourth experimental groups received daily doses of 25 mg saccharin / Kg BW (Sacch.L) and of 100 mg saccharin/ Kg BW (Sacch.H), respectively.The experimental groups received the corresponding sweetener dissolved in water by oral route for 56 consecutive days.The biochemical assays indicated that both NNS exerted a dosedependent significant increase of serum urea and creatinine, compared to the control group.The NNS-treated groups displayed histological changes reflecting dose-dependent nephrotoxic effects.These included glomerular and tubular disorders, and outstanding interstitial haemorrhages and fibroplasia as well.The gene expression levels of the key oncogene (h-Ras) and the tumour suppressor gene (P27) were also estimated, displaying a significant overexpression of the first and a significant downregulation of the second.Taken together, the biochemical and histological alterations, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumour suppressor gene (P27) in all NNS-treated rat groups may indicate a potential risk of carcinogenesis, especially on long-term exposure.