Combined exposure to sarin and pyridostigmine bromide increased levels of rat urinary 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine, biomarkers of oxidative stress.
In this study concentrations of markers of oxidative stress 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OhdG) were determined in rat urine following a single oral dose of pyridostigmine bromide (PB) 13 mg/kg and a single intramuscular dose of sarin 80 microg/kg alone or in combination. Urine samples were collected 16, 24, 48, 72, and 96 h following dosing. Control urine samples of five rats treated with normal saline were also collected at the same time intervals. A combined dose of PB and sarin significantly increased levels of 3-nitrotyrosine and (8-OhdG) starting 48 h after dosing. An increase in the concentration of these markers was not detected following a single dose of PB or sarin alone. Maximal increase in 3-nitrotyrosine and 8-OhdG was detected 48 h after administration of a combination PB and sarin. The results indicate that concurrent exposure to PB and sarin could generate free radical species that may cause oxidative stress in rats. The results may have significant impact if veterans were expose to sarin following an oral dose of PB.
Abu-Qare
A W
AW
Department of Pharmacology and Cancer Biology, Duke University Medical Center, PO Box 3813, Durham, NC 27710, USA.
Abou-Donia
M B
MB
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002138:Calibration; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012524:Sarin / Q000633:toxicity*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000652:urine*
D015415:Biomarkers; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D012524:Sarin; D003849:Deoxyguanosine; D011729:Pyridostigmine Bromide