EFFECT OF THYROIDECTOMY AND ADRENALECTOMY ON CHANGES IN LIVER GLUTATHIONE AND MALONALDEHYDE LEVELS AFTER ACUTE ETHANOL INJECTION

At low concentrations ethanol is metabolized largely by alcohol dehydr ogenase to acetaldehyde, while at higher concentrations a microsomal e thanol oxidising system (MEOS) is involved, namely cytochrome P450 IIE 1, which also probably generates free radical species. In hyperthyroid ism hepatic glutathione stores are depleted and net superoxide anion p roduction occurs. In contrast, in hypothyroidism hepatic glutathione m ay be increased and thus renders the liver less sensitive to alcohol g enerated free radical production. Steroid hormones inhibit lipid perox idation. Sixty male Wistar rats either underwent thyroidectomy, adrena lectomy, or sham procedures. Twenty control animals were pair fed with thyroidectomized animals, whilst another twenty fed ad libitum. An in traperitoneal injection of alcohol (75 mmol/kg) was given 2.5 h prior to sacrifice to half the animals in each group, the remainder receivin g saline. The total hepatic glutathione contents of the pair fed and t he ad libitum groups were not different, but were significantly increa sed by thyroidectomy (p = <0.001). This effect was significantly reduc ed by alcohol (p < 0.01). The sham procedures and dietary restrictions had no effect. The ethanol atone reduced total hepatic glutathione, b ut this only reached statistical significance in the thyroidectomized and sham-adrenalectomized groups. Hepatic malonaldehyde (MDA) levels w ere significantly reduced in the thyroidectomy group but alcohol had n o effect on them. We conclude that hypothyroidism increased hepatic gl utathione status, presumably by reducing radical production by enzyme systems, which would otherwise consume this important scavenger. Long term exposure to ethanol with induction of MEOS is probably required f or it to generate toxic levels of free radical species.