Effects of ethanol on the changes in renal fluid and electrolyte handling and kidney morphology induced by long-term chloroquine administration to rats

This study investigated the effects of long-term chloroquine and ethanol ad ministration on renal fluid and electrolyte handling and kidney structure. Male Sprague-Dawley rats were orally administered with chloroquine diphosph ate (20 mug kg (-1) bw) and/or ethanol (1.6 g kg (-1) bw) every third conse cutive day for 4 weeks. Urine volume and total urinary outputs of Na (+) an d K+ were determined from 24-h samples. For detailed renal studies, rats we re subsequently anaesthetised and challenged with a continuous jugular infu sion of 0.077 M NaCl at 150 mul min (-1) 24 h after the last treatment. Aft er a 3-h equilibration period, urine flow, Na+ and K+ excretion rates were determined over a 4-h period. Plasma concentrations of AVP and aldosterone were measured in unanaesthetised rats and in anaesthetised rats after hypot onic saline infusion. In separate groups, the rats were anaesthetised with an overdose of ether after 4 weeks of treatment and part of the right kidne y was quickly collected and routinely processed for light microscopy. Chlor oquine decreased Nai excretion and increased plasma aldosterone concentrati ons in anaesthetised rats. Ethanol alone did not alter urinary Na+ outputs or aldosterone levels. Combined chloroquine and ethanol increased renal Na excretion, but did not affect plasma aldosterone levels. In unanaesthetise d animals all treatments increased aldosterone levels by comparison with co ntrol rats. Urinary Na+ excretion was decreased by separate administration of either chloroquine or ethanol, but increased by combined treatment. Micr oscopic studies showed that concurrent chloroquine and ethanol administrati on induced extensive damage of the proximal tubule and collecting ducts cel ls. The results of this study suggest that alcohol consumption and chloroqu ine administration could result in diminished renal function possibly due t o alteration of renally active hormones or kidney morphology. (C) 2001 Else vier Science Inc. All rights reserved.