Ethanol-induced changes in membrane ATPases: inhibition by iron chelation

The effect of chronic ethanol intake, with and without an iron chelator, on the activity of rat membrane ATPases was investigated. Using the intragastric feeding model, male Wistar rats (250 g) were fed a liquid diet and ethanol for 1 month. In control pair-fed animals, ethanol was isocalorically replaced by dextrose. In addition to the above groups, two groups of animals (dextrose or ethanol-fed) also received an oral iron chelator (1,2-dimethyl-3-hydroxypyrid-4-one, L₁) (25 mg/kg/day for 30 days). The blood ethanol levels were maintained between 150 and 300 mg/dL. Red cells were washed immediately with ice-cold saline, membranes were prepared, and ATPases were measured. The mean Ca²⁴⁺ pump ATPase in animals fed ethanol was lower than in dextrose-fed controls. In contrast, Na⁺/K⁺ pump ATPase was enhanced following chronic ethanol treatment. The addition of 1₁) to the diet prevented the changes in both the Ca²⁺-ATPase and Na⁺/K⁺-ATPase in ethanol-fed rats. Although the exact mechanism for the prevention of changes in ATPase activity by L₁ is unknown, it is not a result of non-specific interaction between the chelator and membranes. Incubation of purified membranes with different concentrations of L₁ for 60 min at 37° had no effect on the activity of the ATPase. In conclusion, chronic intake of ethanol specifically inhibited Ca²⁺ pump ATPase and enhanced Na⁺/K⁺-ATPase in rat red blood cell membranes. The iron chelator, L₁, corrected both of these ethanol-induced changes.