Gasoline fume inhalation induces apoptosis, inflammation, and favors Th2 polarization in C57BL/6 mice

• Published in: Journal of applied toxicology 2022-07, Vol.42 (7), p.1178-1191
• Main Authors: Nour‐Eldine, Wared, Sayyed, Katia, Harhous, Zeina, Dagher‐Hamalian, Carole, Mehanna, Stephanie, Achkouti, Donna, ElKazzaz, Hanan, Khnayzer, Rony S., Kobeissy, Firas, Khalil, Christian, Abi‐Gerges, Aniella
• Format: Article
• Language: English
• Subjects: Animal tissues; antioxidant enzymes; Apoptosis; Biomarkers; Body weight; Cytokines; Exposure; Gasoline; gasoline inhalation; Health risks; Inflammation; Inhalation; Interleukins; Intoxication; Liver; Lungs; Lymphocytes T; Mitochondria; Molecular modelling; Phenotypes; Respiration; Staining; Th2 polarization; Therapeutic targets; Tumor necrosis factor; Vapors
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4286

Gasoline exposure has been widely reported in the literature as being toxic to human health. However, the exact underlying molecular mechanisms triggered by its inhalation have not been thoroughly investigated. We herein present a model of sub‐chronic, static gasoline vapor inhalation in adult female C57BL/6 mice. Animals were exposed daily to either gasoline vapors (0.86 g/animal/90 min) or ambient air for 5 days/week over 7 consecutive weeks. At the end of the study period, toxic and molecular mechanisms underlying the inflammatory, oxidative, and apoptotic effects triggered by gasoline vapors, were examined in the lungs and liver of gasoline‐exposed (GE) mice. Static gasoline exposure induced a significant increase (+21%) in lungs/body weight (BW) ratio in GE versus control (CON) mice along with a pulmonary inflammation attested by histological staining. The latter was consistent with increases in the transcript levels of proinflammatory cytokines [Interleukins (ILs) 4 and 6], respectively by ~ 6‐ and 4‐fold in the lungs of GE mice compared to CON. Interestingly, IL‐10 expression was also increased by ~ 10‐fold in the lungs of GE mice suggesting an attempt to counterbalance the established inflammation. Moreover, the pulmonary expression of IL‐12 and TNF‐α was downregulated by 2‐ and 4‐fold, respectively, suggesting the skewing toward Th2 phenotype. Additionally, GE mice showed a significant upregulation in Bax/Bcl‐2 ratio, caspases 3, 8, and 9 with no change in JNK expression in the lungs, suggesting the activation of both intrinsic and extrinsic apoptotic pathways. Static gasoline exposure over seven consecutive weeks had a minor hepatic portal inflammation attested by H&E staining along with an increase in the hepatic expression of the mitochondrial complexes in GE mice. Therefore, tissue damage biomarkers highlight the health risks associated with vapor exposure and may present potential therapeutic targets for recovery from gasoline intoxication. Gasoline exposure triggers pulmonary and hepatic inflammation in gasoline‐exposed versus control mice. Gasoline inhalation leads to an increase in interleukins 4, 6, and 10 mRNA levels and a decrease in IL‐12 and TNF‐α, suggesting the skewing toward Th2 phenotype. Gasoline exposure leads to the activation of both intrinsic and extrinsic apoptotic pathways.