title: Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.
abstract: Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.
authors.affiliation: Loma Linda VA Medical Center, Loma Linda, California, USA. Larry.fechter@va.gov
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Fechter
authors.forename: Alisa
authors.initials: A
authors.lastname: Nelson-Miller
authors.forename: Caroline
authors.initials: C
authors.lastname: Gearhart
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015986:Confounding Factors, Epidemiologic; D005978:Glutathione / Q000378:metabolism*; D006838:Hydrocarbons / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D006838:Hydrocarbons; C098607:JP8 aviation fuel; D005978:Glutathione