Long-term consumption of aspartame and brain antioxidant defense status

Abstract

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Anti-neuroinflammatory and antioxidant effects of N-acetyl cysteine in long-term consumption of artificial sweetener aspartame in the rat cerebral cortex

“…The present results propose that ASP (excitotoxic food additives) or its metabolites increase the permeability of BBB and can bypass the blood barrier system and enter the brain in toxic concentrations that produced brain lesions. In accordance with the present results, previous study of the neurotoxic action of ASP on neuronal brain structures, the chronic administration demonstrates the high vulnerability of brain structure and functionality to ASP or to its metabolites' toxicity (Iyyaswamy and Rathinasamy, 2012) and the exposure of brain rats to ASP results in the rapid depletion of cortical GSH followed by an increase in ROS and with a diminishing supply of GSH, there is an accumulation of excessive amounts of ROS and ultimately cell death, (Abhilash et al, 2013).…”

“…ASP is metabolized into three toxic molecules, phenylalanine (50%), aspartic acid (40%), and methanol (10%), which are then absorbed into the circulation and various neurochemical effects of ASP have been associated with increases in and persistence of their metabolites in CNS; those levels are controlled by the blood-brain barrier (BBB) (Humphries et al, 2008). ASP may also be carcinogenic because at least its metabolite diketopiperazine (DKP) can cause cancers in the central nervous system such as glioblastoma, medulloblastomas and meningiomas (Abhilash et al, 2013).…”

“…This form of DKP would undergo a nitrosation process in the stomach producing a type of chemical that could cause brain tumors (Davis et al, 2008). Additionally, long-term consumption of ASP leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathionedependent system (Abhilash et al, 2013).…”

<i>In vitro</i> evaluation of mutagenicity and genotoxicity of sitagliptin alone and in combination with artificial sweeteners

“…Aspartame is an artificial, non-saccharide sweetener and is considered to be closely linked with increased incidence of malignancy of brain tumors. It is suggested that long term use of aspartame might lead to improper antioxidant status of brain mainly through glutathionedependent system involvement [8].…”

Assessment of carcinogenic potential of soft drinks of cola, diet cola, orange and lemon, produced in the city of Uberlândia, Minas Gerais state, Brazil

“…Abhilash et al (2013) showed the effects of chronic aspartame ingestion in Wistar rats which resulted in imbalance in the oxidative states in the brain of the exposed, through a glutathionedependent system. In spite of controversial results for mutagenic and genotoxic profile in different study models, Yılmaz and Uçar (2014) in a revision highlight the genotoxic effects of aspartame, characterizing it as a moderate carcinogenic agent for humans, with positive results for 45% of the epidemiological studies.…”