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

Abstract

Infection caused by Mayaro virus (MAYV) is responsible for causing acute nonspecific fever, in which the ma- jority 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 antioxi- dant 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.