Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice

Abstract

No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway.

Chronic intake of 4-Methylimidazole induces Hyperinsulinemia and Hypoglycaemia via Pancreatic Beta Cell Hyperplasia and Glucose Dyshomeostasis

“…NAS and 4-MEI are the major additives in the soft drinks. NAS are proven to induce hyperglycaemia in animals and humans by augmenting gluconeogenesis 26 , 27 and based on our results, 4-MEI induces the opposite effect with hyperinsulinemic-hypoglycaemia in animals. In our human studies, the cohorts consuming 4-MEI also had suppressed glucose level compared to controls and NAS only consumers.…”

Worsening of Oxidative Stress, DNA Damage, and Atherosclerotic Lesions in Aged LDLr-/- Mice after Consumption of Guarana Soft Drinks

“…Until the present study, there was no evidence that guarana SD could contribute to liver or gastric damage. In parallel, only a few studies have demonstrated a potential risk of hepatotoxicity under chronic exposure to aspartame [76, 77] or acesulfame K [12]. Thus, our data clarify this question by demonstrating that the excessive consumption of carbohydrates (but not guarana per se) is the main contributor to steatosis and oxidative stress in the liver.…”

Histological changes of tongue papillae induced by the artificial sweetener Aspartame and the protective effect of Platelet-rich plasma

“…Although ASP is widely used all over the world in many products, however there was lack of awareness among consumers about its potential toxic effects (25) . Several experimental researches have confirmed the negative effects of ASP consumption on different tissues and organs such as kidney (8) , liver (14,26) , cerebral cortex (27) and salivary glands (28,29) .…”