The effects of silymarin on the attachment and viability of primary cultures of rat hepatocytes.

The effects of the hepatoprotective compound silymarin on hepatocytes in primary culture were studied. Exposure of cells in primary culture (both conventional cells and perivenous or periportal cells isolated by the digitonin-collagenase perfusion technique) to high concentrations of silymarin surprisingly demonstrated that silymarin per se was cytotoxic. Incubation of cells for 18 hr with silymarin at concentrations exceeding 25 mum abruptly increased cell damage, whereas viability decreased in a more linear fashion with increasing concentrations of its major constituent, silybin. Morphologically, cell cultures exposed to silymarin concentrations lower than 20 mum appeared normal, but at higher concentrations intercellular contacts were lost; cells appeared granulated and took up eosin. Silymarin and silybin at these doses were also found to prevent cell attachment. The mechanism responsible for this effect at relatively low concentrations of silymarin during prolonged exposure in the primary cell culture system is not clear at present. The effects of low doses on cell attachment to the matrix suggest an action on the cell membrane and/or on the cytoskeleton.