Proliferation of Smooth ER

This slide is an EM of liver from a rat treated with Phenobarbital. Chronic exposure to substances that are toxic, such as the barbituates that are handled by the cytochrome P450 system, results in a need for increased activity of these detoxification enzymes and the proliferation of the hepatocyte smooth endoplasmic reticulum on which they are located. As the cell becomes better equipped to modify the drugs, this proliferation leads to drug tolerance.