RESUMO
NADPH oxidase enzymes (NOX) are involved in all stages of carcinogenesis, but their expression levels and prognostic value in breast cancer (BC) remain unclear. Thus, we aimed to assess the expression and prognostic value of NOX enzymes in BC samples using online databases. For this, mRNA expression from 290 normal breast tissue samples and 1904 BC samples obtained from studies on cBioPortal, Kaplan-Meier Plotter, and The Human Protein Atlas were analyzed. We found higher levels of NOX2, NOX4, and Dual oxidase 1 (DUOX1) in normal breast tissue. NOX1, NOX2, and NOX4 exhibited higher expression in BC, except for the basal subtype, where NOX4 expression was lower. DUOX1 mRNA levels were lower in all BC subtypes. NOX2, NOX4, and NOX5 mRNA levels increased with tumor progression stages, while NOX1 and DUOX1 expression decreased in more advanced stages. Moreover, patients with low expression of NOX1, NOX4, and DUOX1 had lower survival rates than those with high expression of these enzymes. In conclusion, our data suggest an overexpression of NOX enzymes in breast cancer, with certain isoforms showing a positive correlation with tumor progression.
Assuntos
Neoplasias da Mama , NADPH Oxidases , Humanos , Feminino , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Oxidases Duais/genética , Neoplasias da Mama/genética , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , RNA Mensageiro/genética , Expressão Gênica , NADPH Oxidase 4/genética , NADPH Oxidase 1/genéticaRESUMO
Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels - increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1ß, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.
Assuntos
Antioxidantes , Bócio , Ratos , Feminino , Masculino , Humanos , Animais , Antioxidantes/metabolismo , Peróxido de Hidrogênio , Estresse Oxidativo , Tireotropina , InflamaçãoRESUMO
The non-therapeutic use of the androgenic anabolic steroid Nandrolone Decanoate is popular due to its effects on physical performance and body composition, especially for its lipolytic and anabolic effects associated. However, high doses of such drugs are often associated with a series of pathologies related to unbalanced redox homeostasis, which, in turn, can be linked to inflammation. The oxidative stress onset could deregulate the secretion of cytokines, evidencing a dysfunctional adipocyte. Thus, the aim of this study was to investigate the effect of supraphysiological doses of Nandrolone Decanoate on redox homeostasis of retroperitoneal fatpad of male rats and its relationship with cytokines-based inflammatory signaling. Hydrogen peroxide production was assessed in the retroperitoneal fat pad of adult male rats which received either 10 mg kg of Nandrolone Decanoate or only a vehicle. Also, catalase, superoxide dismutase and glutathione peroxidase activities were measured, together with total reduced thiols and protein carbonylation, as well as IL-1ß, TNF-α, and IL-6 local levels. High doses of Nandrolone Decanoate caused an increase in the hydrogen peroxide production, together with lower activities of the antioxidant enzymes and lower levels of total reduced thiol. There were also higher protein carbonylation and greater levels of IL-1ß, TNF-α, and IL-6 in the treated group compared to control group. Therefore, it was possible to verify that high doses of Nandrolone Decanoate cause oxidative stress and induce higher inflammatory signaling in retroperitoneal fat pad of male rats.