RESUMO
The rapid recovery of smell and taste functions in COVID-19 patients could be attributed to a decrease in interleukin-6 levels rather than central nervous system ischemic injury or viral damage to neuronal cells. To correlate interleukin-6 levels in COVID-19 patients with olfactory or gustatory dysfunctions and to investigate the role of IL-6 in the onset of these disorders, this observational study investigated 67 COVID-19 patients with taste or smell disorders or both, who did not require intensive care admission, admitted at COVID Hospital of Policlinico of Bari from March to May 2020. Interleukin-6 was assayed in COVID-19 patients with taste or smell disturbances at the time of admission and at the time of swab negativization. At the same time, patients have been given a specific survey to evaluate the severity of taste and smell disturbances. Of 125 patients with smell or taste dysfunctions at onset of disease, 67 fulfilled the inclusion criteria, while 58 were excluded because 35 of them required intensive care admission, 5 were unable to answer, 5 died, 7 had finished chemotherapy recently, and 5 refused to participate. The evaluation of taste and smell disorders was carried out using a survey performed at the time of admission and at the time of swab negativization. Sinonasal outcome test 22 (SNOT-22) was used as a reference for olfactory function assessment, and Taste and Smell Questionnaire Section of the US NHANES 2011-2014 protocol (CDC 2013b) was used as reference for gustatory function assessment. A venous blood sample was taken for each patient to measure IL-6 levels upon entry and at swab negativization. Interleukin-6 levels in COVID-19 patients in relation to olfactory or gustatory disorders were correlated from the time of their admission to the time of swab negativization. Statistically significant correlations were obtained between the decrease of interleukin-6 levels and the improvement of smell (p value < 0.05) and taste (p = 0.047) functions at swab negativization. The acquired results demonstrate the key role of interleukin-6 in the pathogenesis of chemosensitive disorders in COVID-19 patients.
Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Interleucina-6/sangue , Transtornos do Olfato/sangue , Pneumonia Viral/sangue , Distúrbios do Paladar/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Interleucina-6/fisiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , SARS-CoV-2 , Paladar/fisiologia , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/etiologiaRESUMO
In this work, we have investigated the effects of nutritional antioxidants as antidegenerative agents on glutamate-induced apoptosis in primary cultures of cerebellar granule neurons (CGNs). Glutamate-induced apoptosis is also associated with intracellular [Ca(2+)]i overload, generation of reactive oxygen species (ROS), depression of cell energy metabolism, cytochrome c release, and increase in caspase-3 activity. Pretreatment (3 h) with red wine extract (5 microg/mL) and ascorbic acid (30 microM) blocks glutamate-induced apoptosis in CGNs. In vivo experiments carried out on transgenic mice expressing the human mutated Cu, Zn superoxide dismutase (SOD1) G93A (mSOD1(G93A)) show that mice fed with lyophilized red wine have significantly increased survival as compared to control, untreated animals.
Assuntos
Apoptose/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Vinho , Animais , Cálcio , Caspase 3/metabolismo , Células Cultivadas , Citocromos c/metabolismo , Ácido Glutâmico/toxicidade , Humanos , Camundongos , Camundongos Transgênicos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Análise de SobrevidaRESUMO
Primary cultures of cerebellar granule neurons (CGNs) were prepared from 8-day-old Wistar rats, and maintained in an appropriate medium containing a high (25 mM) concentration of KCl. To induce apoptosis, culture medium was replaced with serum-free medium (containing 5mM KCl) 8 days after plating. Apoptosis was measured by the terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end-labeling (TUNEL) method, and by flow cytometry. Since there is evidence that an increased formation of reactive oxygen species (ROS) is involved in the apoptosis induced by low K(+) (5mM) concentrations, the potential anti-apoptotic effect of caffeic acid phenethyl ester (CAPE), a potent flavonoid antioxidant, was tested in this experimental model. It was found that CAPE (10 microg/ml) promoted cell survival and was capable of blocking the apoptotic process as assayed by both TUNEL and flow cytometric methods. The same concentration of CAPE prevented the formation of ROS induced by low K(+). Since there is evidence that low K(+)-induced apoptosis in CGNs is associated with a drop in intracellular Ca(2+) concentration ([Ca(2+)](i)), activation of the cell death effector proteases caspase-3 and caspase-9, and of the transcription factor nuclear factor kappa B (NF-kappaB), the interference of CAPE with these purported mediators of apoptosis was also evaluated. It was found that CAPE did not interfere with the marked decrease in [Ca(2+)](i) induced by low K(+), whereas it completely blocked caspase-3, caspase-9, and NF-kappaB activation. It is concluded that CAPE could exert its anti-apoptotic effect in CGNs by blocking ROS formation and by inhibiting caspase activity.