Sucrose and ethanol inhibit albumin synthesis; sucrose via an osmotic mechanism and ethanol during its metabolism. The present study was undertaken to compare the effects of both of these agents on albumin synthesis and secretion, and to see if ethanol inhibition could be related to an osmotic effect.
Male, fed rabbits served as liver donors in all studies. There were a total of 35 studies: 13 control; 10 ethanol (39 to 52 mM); 4 cycloheximide (0.5 mM), and 8 sucrose (1%). Plasma volume was measured with 125I-albumin (human) and extracellular volume measured with either 99mTc diethylenetriamine pentaacetic acid or [14C]sucrose. During perfusion, rabbit albumin content in the perfusate was measured immunologically every 15 to 30 min for 225 min. Interstitial albumin efflux was measured by the rate of appearance in the perfusate of 125I-albumin given to 10 other rabbits 3 days prior to hepatic removal and perfusion.
During the initial 75 min of perfusion, 74% of the in vivo equilibrated exchangeable 125I-albumin appeared in the perfusate, and during this period the rabbit albumin that entered the perfusate was taken to represent efflux from the interstitial volume plus synthesis. Rabbit albumin appearing in the perfusate during the later period of 150 min was taken to represent mainly synthesis and was used to calculate the amount of albumin that would be synthesized in 75 min. The difference between these two values would be hepatic interstitial albumin appearing in the perfusate. Acute ethanol exposure reduced hepatic extracellular volume from 18.4 ± 0.3 to 14.1 ± 0.2 ml per 100 gm wet liver weight, did not significantly alter hepatic plasma volume (8.4 ± 0.3 vs. 7.5 ± 0.2 ml in alcohol studies) and reduced hepatic interstitial volume from 10.0 ± 0.4 to 6.6 ± 0.3 ml. Sucrose infusions in eight rabbits did not alter hepatic extracellular volume, averaging 17.2 ± 0.8 ml, nor were plasma volume (mean = 8.7 ± 0.5 ml) and calculated hepatic interstitial volume (mean = 8.5 ± 0.4 ml) significantly altered. The amount of albumin (mg per 100 gm wet liver weight per hr) released from control livers during the first 75 min averaged 48 ± 3 mg, decreased to 36 and 38 mg with ethanol and cycloheximide, respectively, but was not effected by sucrose, even though all of these test substances reduced synthesis during the later time periods (T-75 to T-225). The synthetic rates for this time period were 27 mg per 100 gm wet liver weight per hr in controls, 9.5 mg in ethanol studies, 6.4 mg in the cycloheximide studies and 12.3 mg in the sucrose studies. Ethanol and cycloheximide, thus, must have lowered albumin synthesis nearly immediately, but sucrose required a longer exposure.