TY - JOUR
T1 - Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model
AU - Iyaswamy, Ashok
AU - Wankhar, Dapkupar
AU - Loganathan, Sundareswaran
AU - Shanmugam, Sambantham
AU - Rajan, Ravindran
AU - Rathinasamy, Sheeladevi
N1 - Funding Information:
The authors are grateful to the suggestions provided by Dr. NJ Parthasarathy. The authors are grateful to the help given by the Molecular Laboratory, Department of Genetics and Endocrinology for providing facilities to carry out the work. The financial assistance provided by the Indian Council of Medical Research File. No. 3/1/2/29/Nut./2012/Dated 29-09-2013 for Senior Research Fellow is gratefully acknowledged. We thank Mr. GS. Sravan for his language check on this manuscript. I acknowledge the University of Madras for providing the infrastructure to conduct the research.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Aspartame
KW - Free radical
KW - Hepatic injury
KW - Liver function test
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=85020816028&partnerID=8YFLogxK
U2 - 10.1016/j.jnim.2017.06.002
DO - 10.1016/j.jnim.2017.06.002
M3 - Journal article
AN - SCOPUS:85020816028
SN - 2352-3859
VL - 8
SP - 41
EP - 50
JO - Journal of Nutrition and Intermediary Metabolism
JF - Journal of Nutrition and Intermediary Metabolism
ER -
