PMID- 21822758 OWN - NLM STAT- MEDLINE DCOM- 20120626 LR - 20211020 IS - 1476-3524 (Electronic) IS - 1029-8428 (Linking) VI - 21 IP - 3 DP - 2012 Apr TI - Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice. PG - 245-55 LID - 10.1007/s12640-011-9264-9 [doi] AB - This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS; 100 mug/kg) in mice. Aspartame (0.625-45 mg/kg) was given via subcutaneous route at the time of endotoxin administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis factor-alpha (TNF-alpha) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7-32.8%, decreased GSH by 25.6-31.6%, and increased TNF-alpha by 16.7-44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline, and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration of LPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by 21.6 and 31.1%, respectively; increased brain TNF-alpha by 340.4%, and glucose by 39.9%, and caused marked increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%, respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5-16.9%, nitrite by 12.6-20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS, nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mild systemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver. FAU - Abdel-Salam, Omar M E AU - Abdel-Salam OM AD - Department of Toxicology and Narcotics, National Research Centre, Tahrir St., Dokki, Cairo, Egypt. omasalam@hotmail.com FAU - Salem, Neveen A AU - Salem NA FAU - Hussein, Jihan Seid AU - Hussein JS LA - eng PT - Journal Article DEP - 20110806 PL - United States TA - Neurotox Res JT - Neurotoxicity research JID - 100929017 RN - 0 (Biogenic Monoamines) RN - 0 (Lipopolysaccharides) RN - 0 (Sweetening Agents) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - 333DO1RDJY (Serotonin) RN - GAN16C9B8O (Glutathione) RN - IY9XDZ35W2 (Glucose) RN - VTD58H1Z2X (Dopamine) RN - X4W3ENH1CV (Norepinephrine) RN - Z0H242BBR1 (Aspartame) SB - IM MH - Animals MH - Aspartame/*pharmacology MH - Biogenic Monoamines/*metabolism MH - Brain/*drug effects/metabolism MH - Dopamine/metabolism MH - Glucose/metabolism MH - Glutathione/metabolism MH - Lipid Peroxidation/drug effects MH - Lipopolysaccharides/*pharmacology MH - Liver/drug effects/metabolism MH - Male MH - Mice MH - Nitric Oxide/metabolism MH - Norepinephrine/metabolism MH - Oxidative Stress/*drug effects MH - Serotonin/metabolism MH - Sweetening Agents/*pharmacology MH - Thiobarbituric Acid Reactive Substances/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2011/08/09 06:00 MHDA- 2012/06/27 06:00 CRDT- 2011/08/09 06:00 PHST- 2011/07/05 00:00 [received] PHST- 2011/07/28 00:00 [accepted] PHST- 2011/07/27 00:00 [revised] PHST- 2011/08/09 06:00 [entrez] PHST- 2011/08/09 06:00 [pubmed] PHST- 2012/06/27 06:00 [medline] AID - 10.1007/s12640-011-9264-9 [doi] PST - ppublish SO - Neurotox Res. 2012 Apr;21(3):245-55. doi: 10.1007/s12640-011-9264-9. Epub 2011 Aug 6.