Silybin Interferes with the Intracellular Replication of Piscirickettsia salmonis in SHK-1 Cells and Confers Protection in Salmo salar

<b>Background/Objectives</b>: The salmon industry plays an important role in the Chilean economy, positioning the country as the second-largest producer of salmonids worldwide after Norway. However, this rapid growth has led to an increase in outbreaks of infectious diseases, which cause significant economic losses to the industry. The pathogen that most affects the salmon industry is the bacterium <i>Piscirickettsia salmonis</i>, accounting for 43.1% of infection-related deaths. In the search for new treatment alternatives against <i>P. salmonis</i>, we have previously reported that the effect of co-incubating silybin at sub-IC50 concentrations decreases the intracellular presence of <i>P. salmonis</i> in SHK-1 cells. <b>Methods</b>: This article evaluates the effect of silybin on the immune response and oxidative stress of SHK-1 cells infected with <i>P. salmonis</i>, as well as the reduction in intracellular bacterial replication during the first 72 h of infection. Furthermore, we assess the ability of silybin administration to modulate the immune response in <i>S. salar</i> and protect against <i>P. salmonis</i> infection. <b>Results</b>: The results show that co-incubation of silybin during infection in SHK-1 cells modulates the expression levels of the genes <i>gsh-px</i>, <i>cat</i>, <i>tnf-α</i>, and <i>il-1β</i> and also decreases the levels of intracellular ROS generated by the infection. Furthermore, the mechanism of action of silybin in SHK-1 cells is related to interference with the intracellular replication of <i>P. salmonis</i> after 72 h of infection and not to adherence or internalization of the bacteria. Finally, silybin is able to generate protection in <i>S. salar</i> infected with <i>P. salmonis</i> independently of stimulation of the immune response. <b>Conclusions</b>: In conclusion, silybin administration may be an effective treatment against <i>P. salmonis</i> in salmonids; however, further studies are needed to clarify the mechanism of action.