Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model

Ashok Iyaswamy*, Dapkupar Wankhar, Sundareswaran Loganathan, Sambantham Shanmugam, Ravindran Rajan, Sheeladevi Rathinasamy

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

5 Citations (Scopus)


This study assesses the effect of long-term intake of aspartame on liver function and apoptosis signaling pathway in the Wistar albino rats. Several reports have suggested that methanol is one of the major metabolites of Aspartame. Non-primate animals are usually resistant to methanol-induced metabolic acidosis due to high levels of hepatic folate content; hence a folate deficiency model was induced by treating animals with methotrexate (MTX) prior to aspartame exposure. The aspartame treated MTX animals exhibited a marked significant increase in hepatic alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) activity compared to controls. Aspartame treated MTX animals additionally exhibited down-regulation of genes namely B-cell lymphoma 2 (Bcl2) expression and up-regulation of Bcl-2-associated X protein (Bax), Fas-associated protein with death domain (FADD) and Caspase 3, 9 genes and apoptotic protein expression, indicating the augmentation of hepatic apoptosis. Nuclear condensation, micro vacuole formation in the cytoplasm and necrosis were observed in the liver of the aspartame treated animals on histopathology evaluation. Additionally, Immunohistochemical analysis revealed a significant increase in positive cells expressing Fas, FADD, Bax and Caspase 9 protein, indicating an increase in apoptotic protein expression in the liver. Thus, Aspartame may act as a chemical stressor which alters the functional status of liver, leading to hepatotoxicity.

Original languageEnglish
Pages (from-to)41-50
Number of pages10
JournalJournal of Nutrition and Intermediary Metabolism
Publication statusPublished - Jun 2017

Scopus Subject Areas

  • Endocrinology, Diabetes and Metabolism
  • Food Science
  • Nutrition and Dietetics

User-Defined Keywords

  • Apoptosis
  • Aspartame
  • Free radical
  • Hepatic injury
  • Liver function test
  • Stress


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