Adil Aldhahrani; Mohamed M. Ahmed; Maram H. Abduljabbar; Razaz A. Felemban; Alaa A. H. Alorabi & Mohamed E. Alkafafy

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 dose- dependent 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.

KEY WORDS: Aspartame; Saccharin; Rat; Kidney; Nephrotoxicity; h-Ras; P27.

ALDHAHRANI, A.; AHMED, M. M.; ABDULJABBAR, M. H.; FELEMBAN, R. A.; ALORABI, A. A. H. & ALKAFAFY, M. E. Nephrotoxic impacts of aspartame and saccharin in Wistar rat model: Biochemical, molecular and histopathological approach. Int. J. Morphol., 43(3):871-979, 2025.