Depth of invasion of oral squamous cell carcinoma in Nos2-knockout mice correlated to alterations in systemic inflammatory markers following 4NQO treatment.

BACKGROUND: Peripheral blood analysis is a non-invasive and low-cost technique of prognostic value for several diseases, including oral cancer. Considering the role of inducible nitric oxide synthase in tumor-associated inflammation, this study purposed to evaluate the influence of this enzyme on peripheral blood parameters and systemic inflammatory biomarkers during murine oral carcinogenesis. METHODS: A 50 µg/mL solution of 4-nitroquinoleine-N-oxide was provided to 15 C57BL/6J (Nos2+/+ ) and 16 B6.129P2-Nos2tm1Lau /J (Nos2-/- ) for 16 weeks. Animals were followed for 8 weeks after treatment. Blood samples and tongues were collected for hematological and histopathological analyses. Red blood cells, white blood cells, and platelet cell parameters were analyzed. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index were also calculated. The depth of invasion of all carcinomas was measured. RESULTS: Differences were found in several blood parameters. The depth of invasion in Nos2-/- was lower than in Nos2+/+ (p = 0.009), and strong correlations were found between depth of invasion and neutrophil count (ρ = -0.68, p = 0.017), lymphocyte count (ρ = 0.72, p = 0.011), neutrophil-to-lymphocyte ratio (ρ = -0.65, p = 0.025), platelet-to-lymphocyte ratio (ρ = -0.73, p = 0.013), and systemic immune-inflammation index (ρ = -0.67, p = 0.037) in Nos2-/- mice. CONCLUSION: Inducible nitric oxide synthase seems to have an important role in OSCC invasion and progression, which might be associated to alterations in immune-inflammatory cell dynamics evidenced by peripheral blood and systemic inflammatory biomarkers.

Estudo imunohistoquímico do bulbo olfatório de ratos wistar submetidos a exposição pre-natal aguda com etanol / Imunohistochemical study of the olfactory bulb in wistar rats submited to acute prenatal expossure to ethanol

Os efeitos do uso crônico de etanol durante a gravidez sobre a morfologia e as funções do sistema neural são conhecidos na literatura, mas os efeitos do uso agudo de etanol em momentos críticos da gravidez ainda precisam ser esclarecidos. A exposição pré-natal crônica ao etanol tem sido associada a várias anormalidades em fetos e neonatos, como alterações na densidade neuronial e heterotopia de neurônios da zona sub-ventricular do telencéfalo, no bulbo olfatório. Neste trabalho nós estudamos os efeitos da utilização pré-natal aguda de etanol (3 doses de 3 g/kg de peso corporal) no décimo-segundo dia de vida intrauterina (E12) sobre a morfologia do bulbo olfatório de ratos Wistar no oitavo dia de vida pós-uterina (P8), quando as células na fase de síntese foram marcadas in vivo com bromodesoxiuridina e os animais foram sacrificados para observação. Os bulbos olfatórios apresentaram uma diminuição significante na densidade neuronial, como também é observado na síndrome alcoólica fetal decorrente da exposição materna crônica ao etanol durante a gravidez. Estes efeitos poderiam justificar problemas na sensibilidade olfatória de neonatos cujas mães sofreram exposição aguda ao etanol durante a gravidez.