Resumo Introdução: A rinite gestacional é um distúrbio comum da otorrinolaringologia relacionado a hormônios sexuais. Existem alguns estudos epidemiológicos e fisiológicos sobre rinite gestacional, mas as alterações histopatológicas e biomoleculares ainda não foram estudadas completamente. Objetivo: Os receptores VPAC1 e VPAC2 são conhecidos por seu papel na rinite alérgica. Por outro lado, a ativação da alergia subclínica tem sido sugerida na fisiopatologia da rinite gestacional. Portanto, objetivamos comparar o padrão fisiológico e gestacional da expressão de VPAC1 e VPAC2 na mucosa nasal de ratos. Método: Vinte ratas fêmeas Wistar albinas adultas foram incluídas no estudo. Os dois grupos foram divididos em 10 ratas; controle (grupo A) e 10 ratas prenhes (grupo B). Elas foram alimentadas ad libitum e abrigadas em temperatura ambiente (22° ±2° C). Sacrificamos as ratas no 20° dia de gestação por injeção intraperitoneal de 400 mg/kg de sódio-pentobarbital. Em seguida, foram coletados 10 a 15 mL de sangue e as amostras foram reservadas para a detecção dos níveis séricos de estradiol e progesterona pelo método Elisa. O septo nasal foi ressecado e dividido em 2 para análises imuno-histoquímicas e testes de reação em cadeia da polimerase em tempo real, RT-PCR, de VPAC1 e VPAC2. Resultados: VPAC1 e VPAC2 foram encontrados em todas as camadas da amostra septal, mas a imunocoloração do epitélio de superfície foi mais distinta nas amostras de ambos os grupos. Demonstramos maior intensidade geral de coloração no grupo gestante. A reação de polimerase em cadeia revelou aumento significante na expressão de VPAC1 (p = 0,023) e VPAC2 (p = 0,021) no grupo gestante quando comparado ao grupo controle. Além disso, demonstramos um efeito up-regulador do estradiol e progesterona na expressão do receptor peptídeo intestinal vasoativo. Conclusão: A up-regulação gestacional dos receptores VPAC1 e VPAC2 nasais foi demonstrada tanto por reação de polimerase em cadeia quanto por análise imuno-histoquímica. Esses achados corroboram a hipótese de que a rinite gestacional é causada pela ativação de alergia subclínica presente antes da gestação.

Abstract Introduction: Pregnancy rhinitis is a common sex hormone-related otorhinolaryngological disorder. There are some epidemiological and physiological studies on pregnancy rhinitis, but histopathological and biomolecular changes have not been studied thoroughly. Objectives: The receptors VPAC1 and VPAC2 are known for their roles in allergic rhinitis. On the other hand, activation of subclinical allergy has been suggested in the pathophysiology of pregnancy rhinitis. Therefore, we aimed to compare the physiological and gestational pattern of VPAC1 and VPAC2 expression in rat nasal mucosa. Methods: Twenty adult Wister albino female rats were enrolled into the study. Two groups constituted as 10 control (group A) and 10 pregnant (group B) rats. They were fed ad libitum and sheltered at room temperature (22°±2°C). The rats were sacrificed at the 20th day of gestation by intraperitoneal injection of 400mg/kg Na-pentobarbitone. Then, 10 – 15 mL of blood was taken, and samples were reserved for the detection of serum estradiol and progesterone levels by ELISA test. The nasal septum was resected and divided in half for immunohistochemical analyses and real time polymerase chain reaction testing of VPAC1 and VPAC2. Results: VPAC1 and VPAC2 were found to be in all layers of septal specimens, but the immunostaining of surface epithelium was more distinct in specimens of both groups. We demonstrated higher overall staining intensity in the pregnant group. PCR revealed significant increase in expression of VPAC1 (p = 0.023) and VPAC2 (p = 0.021) in pregnant group when compared with control group. In addition, we demonstrated upregulatory effect of estradiol and progesterone on the vasoactive intestinal peptide receptor expression. Conclusions: Gestational up-regulation of nasal VPAC1 and VPAC2 was shown both by PCR and immunohistochemical analysis. These findings support the hypothesis that PR is caused by the activation of subclinical allergy that is present before pregnancy.

SUMMARY OBJECTIVE: We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats. METHODS: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed. RESULTS: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05). CONCLUSIONS: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.