Pancreatic disease: a casualty of hepatic "detoxification"?

Abstract

The rising incidence of pancreatic disease suggests that environmental factors are involved: the susceptibility of only a small proportion of individuals indicates that host factors are important. It is postulated that aberrant function of the hepatic mixed-function oxidases (MFOs) is the root cause of pancreatic disease. The MFO system processes numerous chemicals and is induced by many of them: suspected aetiological factors in pancreatic disease (drugs, cigarettes, alcohol, coffee) are inducers of the system. The degree of inducibility is governed by an individual's genetic endowment, and induction is facilitated by an ample supply of dietary polyunsaturated fatty acids. An increase in dietary polyunsaturated fat might explain the rising incidence of pancreatic disease. It is suggested that the products of hepatic "detoxification" (lipid peroxidation products, toxic epoxides, carcinogens, free radicals) are excreted in bile, reflux into the pancreatic duct, and induce pathological changes. Factors that promote reflux would increase risk of disease only when bile contains excessive amounts or abnormal types of reactive intermediates.