The Effect of Chronic Ethanol Consumption on the Rate of Whole Animal and Perfused Liver Oxygen Consumption

Summary

In order to assess the thyroid state of rats chronically treated with an alcohol containing diet, the rate of minimal oxygen consumption, the level of serum thyroid hormones and the rate of perfused liver oxygen consumption were measured. In no case was there any evidence for alcohol induced systemic or hepatic hyperthyroidism or hypermetabolism.

Observations of increased rates of oxygen consumption in liver slices from rats which had chronically consumed an ethanol containing diet led Israel and his co-workers to suggest that a condition of thyroid mediated hypermetabolism is present in livers of chronically alcoholic rats (Videla et al., 1973; Israel et al., 1975). This observation was further supported by observations of increased ouabain sensitivity of liver slice respiration, increased levels of ∝-glycerophosphate dehydrogenase, an increased uptake of thyroxine by liver slices, and increased rates of perfused liver oxygen consumption in the presence of ethanol (Videla et al., 1973; Israel et al., 1975; Thurman et al., 1976). It was consecutively proposed that the increased rates of oxygen consumption in livers from rats chronically fed alcohol resulted in hypoxic degeneration (Israel et al., 1975). However, with the exception of the observation of increased oxygen uptake by chronically alcoholic livers perfused in the presence of ethanol (Thurman et al., 1976), the findings that supported these hypotheses have not been observed in subsequent studies employing hepatocytes from alcoholic rats (Cederbaum et al.., 1978; Gordon, 1977; Christensen et al., 1977). In spite of the uncertainties raised by these later studies, clinical trials have been conducted to test the therapeutic effectiveness of the antithyroid drug, propylthiouracil, in treating alcoholic hepatitis (Orrego et al., 1979). The reports of these trials indicate reduced morbidity for patients admitted with sub-normal triiodothyronine levels, suggesting the theoretical basis for improvement is poorly understood. Since, uncertainties in the original observations have been extended to a clinical setting, it seems important that the contribution of thyroid or non-thyroid mediated hepatic hypermetabolism to alcoholic liver disease be reassessed as quickly as possible. Therefore, in order to delineate the systemic and hepatic thyroid state of chronic alcoholic rats, the rate of minimal oxygen consumption, serum thyroid hormone levels, and the rate of perfused liver oxygen consumption have been measured.