Abstract
Aspartame, a “first generation sweetener”, is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg·day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame [40 mg/(kg·day)] or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes.
Highlights
Aspartame, an artificial sweetener in low-calorie foods and soft drinks, is a low calorie option for people who should or need to limit their sugar intake
Aspartame for 90 days caused a significant increase in the mRNA transcript levels of hsp70 in the spleen, thymus and lymph node of both the rats fed a normal diet and rats fed with the folate deficient diet compared to their control counterparts
During the course of the present study, we observed that there was up regulation of hsp70 gene expression in immune organs at both the RNA expression level and the protein expression level (Western blot and immunohistochemistry), which may be a primary biological response to the oxidative stress caused by aspartame and its metabolites
Summary
An artificial sweetener in low-calorie foods and soft drinks, is a low calorie option for people who should or need to limit their sugar intake. Aspartame does not contribute to tooth decay and is approximately 200 times sweeter than sugar. Aspartame is currently used in over 6,000 products in over 120 countries worldwide. It consists of 2 amino acids, aspartic acid and phenylalanine, in addition to methanol. Phenylal1anine is believed to mediate or exacerbate hepatic encephalopathy[1]. Safety issues that have been raised include possible toxicity from methanol and/or its systemic metabolites, formaldehyde and formic acid, which are corrosive to mucous membranes and can result in liver and kidney injury
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