Oluwashola Samuel Olaolu, Federal university of Ouro preto

Oluwashola Samuel Olaolu 1 , Marília Bueno da Silva Menegatto 2 , Rafaela Lameira Souza Lima 2 , Ariane Coelho Ferraz 2 ,Felipe Rocha da Silva Santos 3 , Danielle cunha Teixeira 3 , Vivian Vasconcelos Costa 3 , Cintia Lopes de Brito Magalhães 1,2 1 Universidade Federal de Ouro Preto; 2 Universidade Federal de Ouro Preto; 3 Universidade Federal de Minas Gerais

Discovering & Evolving

Yellow fever virus (YFV) infection exhibits variable clinical severity in humans, from mild febrile illness to life-threatening systemic disease. Despite the availability of an effective vaccine, the molecular mechanisms underlyingYFV-induced hepatic pathogenesis remain poorly understood. Our prior studies demonstrated that oxidative stresscontributes to YFV pathogenesis and identified silymarin as a potential antioxidant and hepatoprotective agent. In thisstudy, we evaluated the antioxidant, hepatoprotective and anti-inflammatory properties of silymarin against YFVinfection using in vitro (HepG2) and in vivo (AG129) experimental model. To evaluate the therapeutic potential ofsilymarin against YFV infection, we established an experimental model using 6-week-old AG129-knockout mice.Animals were inoculated with YFV intravenously and treated with silymarin at 200 mg/kg/day, administered every 12hours through gavage. Preliminary results from infected and treated animals showed reduced viral load in the liver.Histopathology showed that silymarin was able to reduce inflammation in the liver, though liver enzymes ALT and ASTwere not reduced significantly. For the cells, results revealed a significant decrease in Reactive Oxygen Species levels at4 days post-infection (dpi) in silymarin-treated cells. When measuring oxidative parameters at 4 dpi, treatment withsilymarin resulted in a decrease in lipid peroxidation and carbonyl protein. Furthermore, there was a significant increasein the activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, indicating an antioxidantenvironment. Therefore, our results show that silymarin restores redox homeostasis, in addition to having antiviral andanti-inflammatory action against YFV infection, making this herbal medicine a promising therapeutic agent againstYFV infection.