Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain

Iyaswamy Ashok, Rathinasamy Sheeladevi*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

51 Citations (Scopus)


Aspartame, an artificial sweetener, is very widely used in many foods and beverages. But there are controversies about its metabolite which is marked for its toxicity. Hence it is believed to be unsafe for human use. Previous studies have reported on methanol exposure with involvements of free radicals on excitotoxicity of neuronal apoptosis. Hence, this present study is proposed to investigate whether or not chronic aspartame (FDA approved Daily Acceptable Intake (ADI),40mg/kg bwt) administration could release methanol, and whether or not it can induce changes in brain oxidative stress status and gene and protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax and caspase-3 in the rat brain region. To mimic the human methanol metabolism, Methotrexate (MTX)-treated Wistar strain male albino rats were used and after the oral administration of aspartame, the effects were studied along with controls and MTX-treated controls. Aspartame exposure resulted with a significant increase in the enzymatic activity in protein carbonyl, lipid peroxidation levels, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase activity in (aspartame MTX)-treated animals and with a significant decrease in reduced glutathione, glutathione reductase and protein thiol, pointing out the generation of free radicals. The gene and protein expression of pro apoptotic marker Bax showed a marked increase whereas the anti-apoptotic marker Bcl-2 decreased markedly indicating the aspartame is harmful at cellular level. It is clear that long term aspartame exposure could alter the brain antioxidant status, and can induce apoptotic changes in brain.

Original languageEnglish
Pages (from-to)820-831
Number of pages12
JournalRedox Biology
Publication statusPublished - Apr 2014

Scopus Subject Areas

  • Organic Chemistry
  • Clinical Biochemistry

User-Defined Keywords

  • Antioxidant
  • Apoptosis
  • Aspartame
  • Free radical
  • Mitochondria
  • Oxidative stress


Dive into the research topics of 'Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain'. Together they form a unique fingerprint.

Cite this