Age-associated oxidative macromolecular damages in rat brain regions: role of glutathione monoester.
The generation of reactive oxygen species (ROS) and resultant oxidative stress has been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases. We have evaluated the efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on glutathione, ROS, superoxide anion production, lipid peroxidation (LPO), protein carbonyls, thiol status, oxidative DNA damage products such as 8-hydroxy deoxy guanosine and DNA protein cross-links in discrete brain regions of young and aged rats. An age associated increase in ROS, superoxide anion production, LPO, protein oxidation, and DNA damage products in cortex, striatum, and hippocampus was observed which was reversed by GME. Contradictorily, a decline in the levels of glutathione, total thiol, and nonprotein and protein thiols was observed which was also reversed upon GME administration. These findings suggest that GME administration inhibits free radical-induced oxidative macromolecular damage in aged rats and thereby protects the brain from ROS.
Murali
Ganesan
G
Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai - 600 113, India. biomurali@gmail.com
Panneerselvam
Chinnakkannu
C
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000188:drug therapy / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013053:Spectrophotometry; D013481:Superoxides / Q000378:metabolism; D016896:Treatment Outcome
D015415:Biomarkers; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013481:Superoxides; C042431:S-ethyl glutathione; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D005978:Glutathione