title: In vitro toxicity assessment of a new series of high energy compounds.
abstract: Hydrazine is an aircraft fuel and propellant used by the US Air Force. Due to its toxicity the Propulsion Directorate of the Air Force Research Laboratory (AFRL/PR) has investigated alternative chemicals to replace hydrazine. AFRL/PR has synthesized a series of high energy chemicals (HECs), primarily hydrazine derivatives and amino containing compounds such as hydrazinium nitrate (HZN), 2-hydroxyethyl-hydrazine nitrate (HEHN), diethyl hydrazine nitrate (DEHN), ethanolamine nitrate (EAN), histamine dinitrate (HDN) and methoxylamine nitrate (MAN) to study as alternative chemical candidates. Although HECs are reliable constituents of powered propellant systems, they constitute an important class of toxic agents to which military and civilian personnel can be exposed. The current study was undertaken to examine the toxicity of HECs in primary hepatocytes in vitro. The effects of short-term exposure (4 h) of hepatocytes to HECs were investigated with reference to viability, mitochondrial function and oxidative stress markers. The results showed a decrease in mitochondrial activity, increase in lactate dehydrogenase (LDH) leakage and depletion of reduced glutathione (GSH) levels. The levels of reactive oxygen species (ROS) increased dose dependently in HZN, MAN and HDN exposed cells. However, there was no induction of ROS generation in EAN, DEHN and HEHN exposed cells. Depletion of GSH in hepatocytes by buthionine sulfoximine (BSO) prior to exposure to HZN increased its toxicity. The results suggest that at least one mechanism of HEC toxicity is mediated through oxidative stress.
authors.affiliation: Air Force Research Laboratory, HEST, Wright-Patterson Air Force Base, OH 45433-7400, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hussain
authors.forename: J M
authors.initials: JM
authors.lastname: Frazier
mesh_terms: D000401:Aircraft; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005648:Fuel Oils; D005978:Glutathione / Q000378:metabolism; D006077:Government Agencies; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006834:Hydrazines / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009566:Nitrates / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014481:United States
chemical_list: D002273:Carcinogens; D005648:Fuel Oils; D006834:Hydrazines; D009566:Nitrates; D017382:Reactive Oxygen Species; C029424:hydrazine; D019328:Buthionine Sulfoximine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione