THE ACUTE EFFECTS OF ETHANOL AND ACETALDEHYDE ON THE SYNTHESIS OF MIXED AND CONTRACTILE PROTEINS OF THE JEJUNUM

An investigation was made into the acute effects of ethanoland acetaldehyde with or without enzyme inhibitors of alcoholdehydrogenase (4-methylpyrazole) and aldehyde dehydrogenase(cyanamide) on fractional rates of protein synthesis of mixedand contractile proteins of the jejunum. Ethanol decreased thefractional rates of mixed and contractile protein synthesis(i.e. k_o defined as the percentage of tissue protein renewedeach day) by -25%. Pretreatment with 4-methylpyrazole followedby treatment with ethanol further reduced mixed and contractilek_o by -30%, when compared with saline plus saline and 4-methylpyrazoleplus saline groups. The greatest reductions in k_o of mixed andcontractile proteins occurred with cyanamide pretreatment followedby ethanol treatment: mixed and contractile protein k_o in thecyanamide plus ethanol group decreased by -60% when comparedwith saline plus saline and cyanamide plus saline groups, whereask_o decreased by -45% when compared with the saline plus ethanolinjected group. Acetaldehyde treatment alone caused no significantinhibition of protein synthesis. However, 4-methylpyrazole pretreatmentplus acetaldehyde treatment significantly reduced mixed andcontractile k_o by -20% when compared with the saline group,and by -15% when compared with the 4-methylpyrazole plus salineand saline plus acetaldehyde groups. These data show that ethanolalone and perhaps high levels of acetaldehyde may be responsiblefor the inhibition of intestinal protein synthesis and relatedpathological derangements, e.g. motility disturbances due toloss of contractile proteins.     

EFFECT OF ACUTE ETHANOL DOSAGE ON NUCLEOTIDE LEVELS IN THE RAT JEJUNUM: RELATIONSHIP TO PROTEIN SYNTHESIS

In previous studies we have shown that ethanol-fed rats generateantibodies reactive with proteins modified by acetaldehyde invitro and that their livers contain proteins modified by acetaldehyde.In this study we demonstrate that the antibodies from theseanimals react with the modified proteins found in their livers.Furthermore, when the antibodies reactive with specific proteinswere isolated, they were found to react with all of the modifiedproteins detected by the whole serum. This suggests that allof the proteins modified by acetaldehyde in vivo carry the sameor similar epitope(s). In addition, antibodies from alcoholicsand a rabbit immunised with proteins modified by acetaldehydein vitro also reacted with the liver cytosolic proteins fromethanol-fed rats. Therefore it appears that similar epitopesare generated in alcoholics as a result of ethanol misuse, inrat liver due to prolonged ethanol feeding and by the in vitromodification procedure used to produce the immunogen for therabbit.     

RATES OF PROTEIN SYNTHESIS IN DIFFERENT REGIONS OF THE NORMOTENSIVE AND HYPERTROPHIED HEART IN RESPONSE TO ACUTE ALCOHOL TOXICITY

The objective of study was (a) to investigate whether proteinsynthesis in different regions of the heart (i.e. left and rightatria, left and right ventricles) expressed equal sensitivityto acute ethanol dosage, and (b) to ascertain whether concomitantcardiac abnormalities (i e. experimental hypertrophic heartdisease) exacerbated these responses. Acute ethanol dosage (75mmol/kg body weight. i.p.) to mature male Wistar rats reducedthe fractional rate of protein synthesis (k₅ %/day) in all regions(atria and ventricles) of the normal and overloaded (30 daysaortic constricted) hearts. The responses in k₃ were variable.In normal heart, the atrial tissues showed a slightly greaterdecrease in k₅ (approx. –30%) when compared to the ventricularregions (approx –2O%). The most pronounced effects occurredin the hypertrophied left ventricular tissues where the depressiveeffects of ethanol on the rate of protein synthesis were potentiatedin the presence of hypertrophy (k₃, reduced by approx 40%).Other regions of the overloaded heart did not show additionalsensitivity to the effects of ethanol on protein synthesis inthe presence of chronic hypertension. In conclusion, the deleteriouseffects of ethanol on the left ventricle are additive in thepresence of chronic hypertrophy. These results may have importantimplications for other cardiac abnormalities where there isalso concomitant ethanol exposure.