The
nerve agent VX is one of the most deadly threat agents available in weapons stockpiles for intentional release. While mostly considered a percutaneous toxicant, it can be fatal when aerosolized. The objective of this study was to investigate toxic responses in the lung up to two weeks following a single 10-minute exposure to inhaled
VX. Anesthetized rats were exposed singly and only once to
VX. The nebulization rate in this system was 0.2-0.3 ml per minute with the delivery of a consistent particle size of 2.1 µm. Following exposure, all rats were removed from the
ventilator and allowed to recover in the glovebox for 10-15 minutes. Results showed that inhaled
VX altered several respiratory parameters and caused increased lung resistance up to 6 h post-exposure (PE). There was a trending increase in SOD and
xanthine oxidoreductase (XOR) activities, both of which are indicative of oxidative stress. Based on increased lung tissue p38 signaling, MAP
kinase expression was activated after
VX exposure.
IL-6 expression was also increased at 6 h post-inhalation for the 31.6 mg/m3 exposed group. Innate survival response mechanisms in rats may be present due to increased lung tissue
mRNA AChE expression 6 h after exposure. Immunohistochemistry showed reduced staining for
surfactant D and increased expression of iNOS, indicating that the activation of •NO precursor pathways. Bronchoalveloar lavage fluid (BALF) results from 1 h to 2 weeks PE show that inflammatory cells are highly active as evidenced by the increased production of
cytokines and
chemokines. This is the first study linking
VX-induced
lung injury to a possible innate survival amplification of AChE and possibly compromised immune function. These results could supplement medical treatment strategies with regard to therapeutic approaches against
VX inhalational challenge.