The overall goal is to determine if hypoxia caused by carbon monoxide (CO) contributes to the progression of alcoholic liver disease (ALD). This is especially relevant to the observations that in ALD, cell necrosis and fibrosis takes place around central veins where oxygen tension is lowest. We will administer ethanol and a defined diet by an indwelling gastric cannula. This gives us complete control of diet and alcohol intake so we can maintain high blood levels, adequate nutrition and perfect pair feeding of isocaloric diets to controls. The method of CO exposure that we propose to use also allows perfect control of CO inspired by rats. Five groups of five rats each will form the experimental group. All rats exposed to CO and fed ethanol and liquid diet are pair fed with rats receiving the same diet plus glucose in amounts isocaloric to ethanol. The progression of liver injury will be followed through all phases i.e. fatty liver, necrosis and fibrosis. The amount of fat, necrosis and fibrosis will be compared in experimental and control groups. In addition, correlations will be done between the carboxyhemoglobin levels and progression of liver injury. We anticipate that rats receiving alcohol and breathing CO will develop more severe alcoholic liver disease earlier than rats in other groups. The significance of the information is related to the possible interaction between smoking and alcohol in the pathogenesis of ALD and to provide a basis for such an interaction.
