How does ozone affect mice? - briefly
Ozone exposure triggers pulmonary inflammation, oxidative damage, and reduced lung compliance in laboratory rodents. It also compromises systemic immune responses and diminishes exercise tolerance.
How does ozone affect mice? - in detail
Ozone inhalation produces a dose‑dependent inflammatory response in the respiratory tract of laboratory mice. Acute exposure (0.5–2 ppm for 1–4 h) triggers epithelial injury, neutrophil recruitment, and elevated levels of cytokines such as IL‑6, TNF‑α, and KC. Histological examination reveals epithelial desquamation, mucus hypersecretion, and thickening of the airway wall. Pulmonary function tests show reduced forced expiratory volume and increased airway resistance, indicating airway hyperresponsiveness.
Chronic exposure (0.1–0.5 ppm for 6–12 weeks) leads to persistent oxidative stress. Measurements of glutathione depletion, protein carbonylation, and lipid peroxidation confirm ongoing redox imbalance. Antioxidant enzymes (superoxide dismutase, catalase) are up‑regulated, but insufficient to prevent tissue damage. Fibrotic remodeling appears after prolonged exposure, with collagen deposition in peribronchial regions and increased expression of transforming growth factor‑β.
Systemic consequences extend beyond the lungs. Elevated plasma fibrinogen and C‑reactive protein indicate systemic inflammation. Cardiovascular assessments reveal endothelial dysfunction, reduced nitric‑oxide bioavailability, and heightened blood pressure. In metabolic studies, ozone‑exposed mice exhibit impaired glucose tolerance and altered lipid profiles, suggesting a link between pulmonary oxidative stress and metabolic dysregulation.
Neurobehavioral effects are documented in several paradigms. Open‑field and elevated‑plus‑maze tests show increased anxiety‑like behavior after subchronic exposure. Neuroinflammatory markers (Iba‑1, GFAP) rise in the hippocampus, and synaptic proteins (PSD‑95, synaptophysin) decrease, indicating potential neurotoxicity mediated by peripheral cytokine spillover.
Reproductive outcomes are also affected. Female mice exposed to ozone during estrous cycles display reduced implantation rates and smaller litter sizes. Male fertility declines, with lower sperm count, decreased motility, and increased DNA fragmentation, correlating with oxidative damage in testicular tissue.
Mechanistic investigations identify several pathways:
- Direct oxidation of lipids and proteins in airway epithelium.
- Activation of the NF‑κB signaling cascade, driving transcription of pro‑inflammatory genes.
- Induction of the Nrf2 pathway, attempting to restore redox balance.
- Modulation of the renin‑angiotensin system, contributing to vascular dysfunction.
Experimental design considerations include:
- Selection of exposure concentration and duration to mimic ambient or occupational levels.
- Use of whole‑body versus nose‑only inhalation chambers to control dose distribution.
- Monitoring of ozone concentration with calibrated UV photometric analyzers.
- Inclusion of appropriate control groups (filtered air, sham exposure).
Overall, ozone exposure in mice produces a multifaceted pathology encompassing respiratory injury, systemic inflammation, cardiovascular impairment, metabolic disturbance, neurobehavioral alteration, and reproductive toxicity. The model provides mechanistic insight relevant to human health risk assessment and informs potential therapeutic strategies targeting oxidative and inflammatory pathways.