TY - JOUR
T1 - Oxidant stress evoked damage in rat hepatocyte leading to triggered nitric oxide synthase (NOS) levels on long term consumption of aspartame
AU - Ashok, Iyaswamy
AU - Sheeladevi, Rathinasamy
N1 - Funding Information:
The author is grateful to the suggestion offered by Dr. NJ Parthasarathy and coauthors. The author is grateful to the help given by the Molecular Laboratory, Department of Genetics and Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-113, TN, India. The financial assistance provided by the Indian Council of Medical Research (ICMR) File. No. 3/1/2/29/Nut./2012/Dated 29-09-2013 for Senior Research Fellow is gratefully acknowledged. The University of Madras, Chennai, India is acknowledged for providing the resources to conduct the research.
Publisher Copyright:
© 2015, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC.
PY - 2015/12
Y1 - 2015/12
N2 - This study investigates how long-term (40 mg/kg b.wt) consumption of aspartame can alter the antioxidant status, stress pathway genes, and apoptotic changes in the liver of Wistar albino rats. Numerous controversial reports are available on the use of aspartame as it releases methanol as one of its metabolites during metabolism. To mimic the human methanol metabolism the methotrexate treated rats were included to study the aspartame effects. The aspartame treated methotrexate (MTX animals showed a marked significant increase in the superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and Glutathione peroxidase (GPx) activity in the liver from control and MTX control animals, and showed a significant decrease in reduced glutathione (GSH) and protein thiol in aspartame treated animals. The aspartame treated MTX animals showed a marked significant decrease in the body weight, brain, and liver weight. The aspartame treated MTX animals showed a marked increase in the inducible nitric oxide (iNOS), neuronal nitric oxide (nNOS), c-fos, Heat shock protein (Hsp) 70 Tumour necrosis Factor (TNF)α, caspase 8, c-jun N terminal kinases (JNK) 3 and Nuclear factor kappa B (NFkB) gene expression in the liver from control and MTX control animals. The aspartame treated MTX animals showed a marked increase in the c-fos, Hsp 70, iNOS Caspase 8, and JNK 3 protein expression in the liver from control and MTX control animals indicating the enhancement of stress and apoptosis. The aspartame treated MTX animals showed a streak of marked DNA fragmentation in the liver. On immunohistochemical analysis aspartame treated animals showed brown colored positive hepatocytes indicating the stress specific and apoptotic protein expression. Since aspartame consumption is on the rise among people, it is essential to create awareness regarding the usage of this artificial sweetener.
AB - This study investigates how long-term (40 mg/kg b.wt) consumption of aspartame can alter the antioxidant status, stress pathway genes, and apoptotic changes in the liver of Wistar albino rats. Numerous controversial reports are available on the use of aspartame as it releases methanol as one of its metabolites during metabolism. To mimic the human methanol metabolism the methotrexate treated rats were included to study the aspartame effects. The aspartame treated methotrexate (MTX animals showed a marked significant increase in the superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and Glutathione peroxidase (GPx) activity in the liver from control and MTX control animals, and showed a significant decrease in reduced glutathione (GSH) and protein thiol in aspartame treated animals. The aspartame treated MTX animals showed a marked significant decrease in the body weight, brain, and liver weight. The aspartame treated MTX animals showed a marked increase in the inducible nitric oxide (iNOS), neuronal nitric oxide (nNOS), c-fos, Heat shock protein (Hsp) 70 Tumour necrosis Factor (TNF)α, caspase 8, c-jun N terminal kinases (JNK) 3 and Nuclear factor kappa B (NFkB) gene expression in the liver from control and MTX control animals. The aspartame treated MTX animals showed a marked increase in the c-fos, Hsp 70, iNOS Caspase 8, and JNK 3 protein expression in the liver from control and MTX control animals indicating the enhancement of stress and apoptosis. The aspartame treated MTX animals showed a streak of marked DNA fragmentation in the liver. On immunohistochemical analysis aspartame treated animals showed brown colored positive hepatocytes indicating the stress specific and apoptotic protein expression. Since aspartame consumption is on the rise among people, it is essential to create awareness regarding the usage of this artificial sweetener.
KW - apoptosis
KW - aspartame
KW - hepatocyte
KW - hepatotoxicity
KW - stress specific genes
UR - http://www.scopus.com/inward/record.url?scp=84922138750&partnerID=8YFLogxK
U2 - 10.1016/j.jfda.2014.07.011
DO - 10.1016/j.jfda.2014.07.011
M3 - Journal article
AN - SCOPUS:84922138750
SN - 1021-9498
VL - 23
SP - 679
EP - 691
JO - Journal of Food and Drug Analysis
JF - Journal of Food and Drug Analysis
IS - 4
ER -