Methacrylate uptake by isolated hepatocytes and perfused rat liver

I showed recently (Int. J. Biochem. Cell Biol. 27, 1311-1316, 1995) that methacrylate formed in vivo from methyl methacrylate (a basic component of polymer used in medicine and industry) is very efficiently removed from the blood. To resolve whether the liver is responsible for methacrylate elimination from the blood, methacrylate uptake by isolated hepatocytes and by perfused liver was investigated. For comparative purposes methacrylate uptake by perfused heart was also examined. It has been found that methacrylate is eliminated efficiently both by isolated hepatocytes and by perfused liver. The whole liver eliminated more than 100-fold of this compound compared to the whole heart. If the rate of methacrylate uptake was calculated per gram of tissue, the liver was 10 times more effective than the heart. KCN (2 mM) addition inhibited methacrylate uptake both by the liver and the heart by approximately 40% at 20 min of perfusion. Pretreatment of rats with galactosamine, which causes liver damage, resulted in a significant inhibition of methacrylate uptake. The data presented in this paper suggest that the liver plays a central role in the methacrylate elimination from the blood. From the results published recently and presented in this paper one can conclude that the relatively low toxicity of orally administered methyl methacrylate is the consequence of a rapid ester hydrolysis with the subsequent elimination of methacrylate by the liver. The toxicity of methacrylate (especially towards organs other than the liver) could be increased under conditions leading to liver damage.