Implications of oxidative stress on viral pathogenesis Camini, Fernanda Caetano; da Silva Caetano, Camila Carla; Almeida, Letícia Trindade ...
Archives of Virology,
04/2017, Letnik:
162, Številka:
4
Journal Article, Book Review
Recenzirano
Reactive species are frequently formed after viral infections. Antioxidant defences, including enzymatic and non-enzymatic components, protect against reactive species, but sometimes these defences ...are not completely adequate. An imbalance in the production of reactive species and the body’s inability to detoxify these reactive species is referred to as oxidative stress. The aim of this review is to analyse the role of oxidative stress in the pathogenesis of viral infections and highlight some major therapeutic approaches that have gained importance, with regards to controlling virus-induced oxidative injury. Attention will be focused on DNA viruses (papillomaviruses, hepadnaviruses), RNA viruses (flaviviruses, orthomyxoviruses, paramyxoviruses, togaviruses) and retroviruses (human immunodeficiency virus). In general, viruses cause an imbalance in the cellular redox environment, which depending on the virus and the cell can result in different responses, e.g. cell signaling, antioxidant defences, reactive species, and other processes. Therefore, the modulation of reactive species production and oxidative stress potentially represents a novel pharmacological approach for reducing the consequences of viral pathogenesis.
Non-alcoholic fatty liver disease (NAFLD), the most predominant liver disease worldwide, is a progressive condition that encompasses a spectrum of disorders ranging from steatosis to steatohepatitis, ...and, ultimately, cirrhosis and hepatocellular carcinoma. Although the underlying mechanism is complex and multifactorial, several intracellular events leading to its progression have been identified, including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, and altered endoplasmic reticulum (ER) homeostasis. Phenolic compounds, such as those present in açai (Euterpe oleracea Mart.), are considered promising therapeutic agents due to their possible beneficial effects on the prevention and treatment of NAFLD. We tested in vitro effects of aqueous açai extract (AAE) in HepG2 cells and its influence on oxidative stress, endoplasmic reticulum stress, and inflammation in a murine model of high fat diet-induced NAFLD. In vitro AAE exhibited high antioxidant capacity, high potential to inhibit reactive oxygen species production, and no cytotoxicity. In vivo, AAE administration (3 g/kg) for six weeks attenuated liver damage (alanine aminotransferase levels), inflammatory process (number of inflammatory cells and serum TNFα), and oxidative stress, through the reduction of lipid peroxidation and carbonylation of proteins determined by OxyBlot and modulation of the antioxidant enzymes: glutathione reductase, SOD and catalase. No change was observed in collagen content indicating an absence of fibrosis, stress-related genes in RE, and protein expression of caspase-3, a marker of apoptosis. With these results, we provide evidence that açai exhibits hepatoprotective effects and may prevent the progression of liver damage related to NAFLD by targeting pathways involved in its progression.
•Zika virus (ZIKV) increases the production of reactive oxygen species.•ZIKV negatively regulates the Nrf-2 pathway.•Fullerol reduces oxidative stress caused by ZIKV.•Fullerol restores the negative ...effect on the Nrf-2 pathway.•Fullerol decreases viral multiplication by up to 90%.
Neglected for years, Zika virus (ZIKV) has become one of the most relevant arboviruses in current public health. The recent Zika fever epidemic in the Americas generated a worldwide alert due to the association with diseases such as Guillain-Barré syndrome and congenital syndromes. Among the pathogenesis of ZIKV, recent studies suggest that oxidative stress plays an important role during infection and that compounds capable of modulating oxidative stress are promising as therapeutics. Furthermore, so far there are no specific and efficient antiviral drug or vaccine available against ZIKV. Thus, fullerol was evaluated in the context of infection by ZIKV, since it is a carbon nanomaterial known for its potent antioxidant action. In this study, fullerol did not alter cell viability at the concentrations tested, proving to be inert, beyond to presenting high antioxidant power at low concentrations. ZIKV infection of human glioblastoma increased the production of reactive oxygen species by 60% and modulated the Nrf-2 pathway activity negatively. After treatment with fullerol, both conditions were restored to baseline levels. Additionally, fullerol was able to reduce viral production by up to 90%. Therefore, our results suggest that fullerol as a promising candidate in the control of ZIKV infections, presenting both antioxidant and antiviral action.
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ZIKV infection increases the production of ROS and modulates the Nrf-2 pathway activity negatively. However, with treatment with fullerol, these conditions are restored and occurs a reduction in viral production.
Aim
To analyse the impact of COVID‐19 on professional nursing practice environments and patient safety culture.
Background
The relationship between work environments and patient safety has been ...internationally recognized. In 2020, the pandemic imposed enormous challenges, yet the impact on these variables remains unknown.
Method
This is a quantitative observational study, conducted in a Portuguese hospital, with 403 registered nurses. A self‐completion questionnaire was used.
Results
The impact on the Structure and Outcome components of nursing professional practice environments was positive. Although the Process component remained favourable to quality of care, a negative trend was confirmed in almost all dimensions. The results regarding safety culture showed weaknesses; ‘teamwork within units’ was the only dimension that maintained a positive culture.
Conclusion
Positive responses regarding patient safety were significantly associated with the quality of the nursing professional practice environment. The need to invest in all dimensions of safety culture emerges to promote positive professional environments.
Implications for nursing management
Improving professional nursing practice environments can be achieved through managers' investment in the participation and involvement of nurses in the policies and functioning of institutions, as well as promoting an open, fair and participatory safety culture that encourages reporting events and provides adequate support for professionals.
Mayaro virus (MAYV) is a neglected arbovirus belonging to the family Togaviridae. Its infection leads to Mayaro fever, with clinical manifestations such as fever, myalgia, headache, rash, arthralgia, ...vomiting, and diarrhea. The most prominent complaint from infected person is the long-lasting arthritis/arthralgia. The treatment for Mayaro fever is mainly symptom-based and there are no vaccines or antiviral drugs currently available, thus, natural products with anti-MAYV activity may provide a potential alternative. Recent evidences suggest that oxidative stress plays an important role in MAYV infection and compounds capable of modulating oxidative stress could represent a novel therapeutic approach in modulating MAYV-associated oxidative cellular damage. Silymarin is a complex extracted of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. Its antioxidant and antiviral effects, including its antiviral activity against the Chikungunya virus (CHIKV), prompted us to think whether silymarin could also reduce the replication of the MAYV and restore the pro-oxidant/antioxidant balance in the context of MAYV infection, leading to reduced cellular oxidative stress. We assessed the antiviral activity and protective effect of silymarin against oxidative stress in MAYV-infected HepG2 cells. Cytopathic effect inhibition, viral replication, and plaque reduction assays were used to determine the anti-MAYV activity of silymarin. Additionally, we determined whether silymarin could reduce MAYV-induced oxidative cell damage. Briefly, silymarin exhibited potent antiviral activity against MAYV and reduced MAYV-induced ROS formation and levels of malondialdehyde (MDA) and carbonyl protein, which are biomarkers of oxidative stress. In conclusion, the ability of silymarin to inhibit MAYV replication and attenuate MAYV-induce oxidative stress warrants further investigation of this compound as a novel therapeutic approach to Mayaro fever disease.
•Antiviral activity of sylimarin against Mayaro virus.•Silymarin protects cells from MAYV-induced oxidative stress.•Promising potential of silymarin in the therapeutic of Mayaro fever.
Objective: to analyze the association among happiness at work, family interaction and sociodemographic/professional variables in nurses in the hospital context. Methods: cross-sectional study with a ...convenience sample of 363 nurses. Questionnaires for sociodemographic/professional characterization, Shorted Happiness at Work Scale and Survey Work-Home Interaction Nijmegen were applied. In data analysis and processing, descriptive and inferential statistics were used. Results: moderate levels of happiness at work (4.44±1.15) and moderate to low levels of family interaction (1.02±0.31) were observed. Marital status, leisure activities, place of work, length of professional experience, professional category, working hours and perception of stressful work were associated with happiness at work. Age, gender, children, dependents, leisure activities, length of professional experience, working hours and perception of stressful work were associated with family interaction. Conclusion: nurses showed moderate levels of happiness at work and moderate to low levels of family interaction, associated with specific sociodemographic and professional variables.
Infection caused by Mayaro virus (MAYV) is responsible for causing acute nonspecific fever, in which the majority of patients develop incapacitating and persistent arthritis/arthralgia. Mayaro fever ...is a neglected and underreported disease without treatment or vaccine, which has gained attention in recent years after the competence of Aedes aegypti to transmit MAYV was observed in the laboratory, coupled with the fact that cases are being increasingly reported outside of endemic forest areas, calling attention to the potential of an urban cycle arising in the near future. Thus, to mitigate the lack of information about the pathological aspects of MAYV, we previously described the involvement of oxidative stress in MAYV infection in cultured cells and in a non-lethal mouse model. Additionally, we showed that silymarin, a natural compound, attenuated MAYV-induced oxidative stress and inhibited MAYV replication in cells. The antioxidant and anti-MAYV effects prompted us to determine whether silymarin could also reduce oxidative stress and MAYV replication after infection in an immunocompetent animal model. We show that infected mice exhibited reduced weight gain, hepatomegaly, splenomegaly, anaemia, thrombocytopenia, leukopenia, increased liver transaminases, increased pro-inflammatory cytokines and liver inflammation, increased oxidative damage biomarkers, and reduced antioxidant enzyme activity. However, in animals infected and treated with silymarin, all these parameters were reversed or significantly improved, and the detection of viral load in the liver, spleen, brain, thigh muscle, and footpad was significantly reduced. This work reinforces the potent hepatoprotective, antioxidant, anti-inflammatory, and antiviral effects of silymarin against MAYV infection, demonstrating its potential against Mayaro fever disease.
•Silymarin improves MAYV infection in BALB/c mice.•Silymarin protects mice from liver damage, oxidative stress, inflammation, and virus replication after MAYV infection.•Promising potential of silymarin in the therapeutic treatment of Mayaro fever.
Mayaro virus (MAYV) causes Mayaro fever in humans, a self-limiting acute disease, with persistent arthralgia and arthritis. Although MAYV has a remerging potential, its pathogenic mechanisms remain ...unclear. Here, we characterized a model of MAYV infection in 3-4-week BALB/c mice. We investigated whether the liver acts as a site of viral replication and if the infection could cause histopathological alterations and an imbalance in redox homeostasis, culminating with oxidative stress. MAYV-infected mice revealed lower weight gain; however, the disease was self-resolving. High virus titre, neutralizing antibodies, and increased levels of aspartate and alanine aminotransferases were detected in the serum. Infectious viral particles were recovered in the liver of infected animals and the histological examination of liver tissues revealed significant increase in the inflammatory infiltrate. MAYV induced significant oxidative stress in the liver of infected animals, as well as a deregulation of enzymatic antioxidant components. Collectively, this is the first study to report that oxidative stress occurs in MAYV infection in vivo, and that it may be crucial in virus pathogenesis. Future studies are warranted to address the alternative therapeutic strategies for Mayaro fever, such as those based on antioxidant compounds.
Oropouche virus (OROV) is the aetiological agent of Oropouche fever, the symptoms of which are common to most arboviruses, such as fever, headache, malaise, nausea and vomiting. More than half a ...million people have been infected with OROV since its isolation in 1955. Although Oropouche fever is classified as a neglected and emerging disease, to date, there are no antiviral drugs or vaccines available against the infection and little is known about its pathogenicity. Therefore, it is essential to elucidate the possible mechanisms involved in its pathogenesis. Since oxidative stress plays a pivotal role in the progression of various viral diseases, in this study, redox homeostasis in the target organs of OROV infection was evaluated using an animal model. Infected BALB/c mice exhibited reduced weight gain, splenomegaly, leukopenia, thrombocytopenia, anaemia, development of anti-OROV neutralizing antibodies, increased liver transaminases, and serum levels of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interferon-γ (IFN-γ). The OROV genome and infectious particles were detected in the liver and spleen of infected animals, with liver inflammation and an increase in the number and total area of lymphoid nodules in the spleen. In relation to redox homeostasis in the liver and spleen, infection led to an increase in reactive oxygen species (ROS) levels, increased oxidative stress biomarkers malondialdehyde (MDA) and carbonyl protein, and decreased activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Taken together, these results help elucidate some important aspects of OROV infection that may contribute to the pathogenesis of Oropouche.
•Zika virus induces increase in ROS and biomarkers of oxidative stress, and decrease in antioxidant enzymes.•Zika virus infection triggers oxidative stress cellular response.•Oxidative stress may be ...an important factor in the Zika virus pathogenesis.
The first outbreak of Zika virus (ZIKV) infection in the Americas, especially in Brazil, was reported in 2015. Fever, headache, rash, and conjunctivitis are the common symptoms of ZIKV infection. Unexpected clinical outcomes, such as microcephaly and Guillain-Barré syndrome, have also been reported. The recent spread of ZIKV and its association with severe illness has created an urgent need to understand its pathogenesis and find potential therapeutic targets. Studies show that some viruses, including Flavivirus, trigger oxidative stress, which affects cellular metabolism, viral cycle, and pathogenesis. However, the role of oxidative stress in ZIKV infection needs to be investigated. Here, we analyzed ZIKV infection-triggered oxidative stress and modified antioxidant enzyme activities. U87-MG and HepG2 cells were infected to measure reactive oxygen species (ROS), malondialdehyde (MDA), and carbonyl protein levels, the activities of superoxide dismutase (SOD) and catalase (CAT), and the activation of nuclear factor erythroid 2p45-related factor 2 (Nrf2). ZIKV infection induced a significant increase in ROS, lipid peroxidation, and protein carbonylation products and a significant decrease in SOD and CAT activities accompanied by inhibition of Nrf2 activation in both cell lines. Further, MDA and carbonyl protein levels and SOD and CAT activities were evaluated in the brain and liver of ZIKV-infected C57BL/6 mice, and oxidative stress associated with antioxidant depletion was also found to occur in vivo. Together, our findings indicate the potential use of antioxidants as a novel therapeutic approach to Zika disease, and future studies in this direction are warranted.
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