Quaranta, D. V. | bioRxiv Science

bioRxiv2021

Effects of anesthesia on ozone-induced lung and systemic inflammation

Anesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 hours, 3ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations, and were administered 1-2 hours or 24 hours prior to initiating ozone exposure. We found that Iso given 1-2 hours prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23-24 hours prior to ozone. In contrast, K/X/A given 1-2 hours prior to ozone increased lung and systemic inflammation. Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.

physiology↗

bioRxiv2021

Effects of ozone on sickness and depressive-like behavioral and biochemical phenotypes and their relations to serum amyloid A and kynurenine in blood

Ozone (O3) is an air pollutant which primarily damages the lungs, but growing evidence supports that O3 exposure can also affect the brain. Serum amyloid A (SAA) and kynurenine have been identified as circulating factors that are upregulated by O3, and both can contribute to depressive-like behaviors in mice. However, little is known about the relations of O3 exposure to sickness and depressive-like behaviors in experimental settings. In this study, we evaluated O3 dose-, time- and sex-dependent changes in circulating SAA in context of pulmonary inflammation and damage, sickness and depressive-like behavioral changes, and systemic changes in kynurenine and indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates kynurenine production and contributes to inflammation-induced depressive-like behaviors. Our results in Balb/c and CD-1 mice showed that 3ppm O3, but not 2 or 1ppm O3, caused elevations in serum SAA and pulmonary neutrophils, and these responses resolved by 48 hours. Sickness and depressive-like behaviors were observed at all O3 doses (1-3ppm), although the detection of certain behavioral changes varied by dose. We also found that Ido1 mRNA expression was increased in the brain and spleen 24 hours after 3ppm O3, and that kynurenine was increased in blood. Together, these findings indicate that acute O3 exposure induces transient symptoms of sickness and depressive-like behaviors which may occur in the presence or absence of overt pulmonary neutrophilia and systemic increases of SAA. We also present evidence that the IDO/kynurenine pathway is upregulated systemically following an acute exposure to O3 in mice.

physiology↗