Alcohol action on liver: dose dependence and morpho-biochemical correlations

Since the duration and the dose of alcohol administration are acknowledged as factors that influence the risk of liver injury, it was interesting to compare the character and degree of liver damage following various doses and methods of alcohol administration. In addition, it was assumed to compare the degree of liver damage histologically and on the activity of marker liver enzymes in blood plasma in the same animals.

The several experiments on heterogeneous stock rats with the various daily dose, duration and method of alcohol administration have been carried out. It was found, that the 9-month intake of 15.20% (v/v) ethanol solution as the only source of drinking (the consumption of absolute alcohol was about 4 g/kg/day) did not affect the normal development of animals and did not induce any harmful morphological changes in liver. Moreover, the liver parenchyma looks even better in the context of lesser inflammatory infiltration and vacuolisation of hypatocytes. The activities of the marker liver injury enzymes: alanine and aspartate amino transferases (ALT and AST), alkaline phosphatase (AP) as well as alcohol dehydrogenase (ADH) in blood were also not changed. The intragastric administration 25% (v/v) ethanol (3.5 g/kg twice a day, during 14 days) induced some morphological disturbances in the liver: an extension of blood capillaries and veins in parenchyma and insignificant increasing of the hepatocyte vacuolisation degree (from 0.7 +/- 0.1 points in control to 1.2 +/- 0.2 points in alcohol treated animals). In blood serum, a slight elevation of ADH (from 1.2 +/- 0.2 microM/min/l in control to 1.7 +/- 0.3) and AP (from 236 +/- 19 microM/min/l in control to 278 +/- 25) activities were found. The liquid alcohol diets (mean consumption of absolute alcohol was 14-18 g/kg/day, during a month) induced the more pronounced liver injury: extension of the liver blood vessels, inflammatory infiltration (from 1.1 +/- 0.1 points in control to 2.0 +/- 0.3; P, 0.05) and destruction of hepatocytes (from 0.5 +/- 0.01 points in control to 1.2 +/- 0.1; p < 0.05). Another liquid alcohol diet (mean consumption of absolute alcohol was 20-24 g/kg/day, during a month) induced the expressive hepatocyte vacuolisation (from 0.5 +/- 0.1 points in control to 1.5 +/- 0.2; p < 0.05). In both the experiments, the weaker staining of hepatocyte cytoplasms, basophilia in particular, were found. The activity of blood plasma ADH was insignificantly increased by 47% and 134% and that of AP--by 15% and 38%. The activity of ALT insignificantly increased in the third experiment only and AST remained unchanged. Some correlations among the morphological and biochemical indexes were found in the above experiments: between the degree of hepatocytes vacuolisation and the blood ADH or AP activities (r = 0.62; p < 0.01 and r = 0.54; p < 0.05), accordingly. The oxyphilia intensity correlated with the AST activity (r = 0.64; p < 0.01) and the intensity of hepatocyte basophilia with the ADH activity (r = 0.67; p < 0.01). The negative correlation was also found between the degree of extension of liver blood vessels and the activity of AST (r = -0.57; p < 0.05).

The data obtained confirm the earlier observations concerning the dependence of the degree of liver injury on the dose and manner of alcohol administration as well as great individuality in the liver response to alcohol in heterogeneous stock rats. There are the significant correlations between the some morphological and biochemical markers of alcohol liver injury; among the biochemical markers studied, the ADH activity was the most sensitive.