Oropouche virus infection induces ROS production and oxidative stress in liver and spleen of mice.

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.

Hepatoprotective, antioxidant, anti-inflammatory, and antiviral activities of silymarin against mayaro virus infection.

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.

Zika virus induces oxidative stress and decreases antioxidant enzyme activities in vitro and in vivo.

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.