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277 METABOLIC DISORDERS OF THE LIVER AFTER LONGTERM LOW-DOSE CHOLESTEROL FEEDING IN THE MONGOLIAN GERBIL. A.M.Temmerman*,H.J.Houthoff**,R.Vonk*iR.Ber~er*rB.Koopman***rJ.Fernandes*. * Dept. Paediatrics, University Hospital Groningen, The Netherlands. ** Dept. Pathology, University Groningen. *** Centr. Lab. for Clin. Chem., University Hospital Groningen. The mongolian gerbil is advocated as a good model for the study of elects of dietary lipids [DL) on cholesterol(C) and lipoprotein metabolism. In order to study long term elects of low dose C,we added 0.2%(w/w) C and/or 8.75% of various DL to their stock diet.In particular ani- mals fed with only C added,died within 2 months.After 4 months liver histology of gerbils fed polyunsaturated fat showed granulomas whereas C fed animals had liver disease varying from severe steatosis and liver cell damage with foam cells to micronodular cirrhosis.On C feeding we observed an increase in hepatic C content of 4±0.5mg/g wet weight up to 107±27mg/g,96% as C ester(CE).2 Months after lowering dietary C to 0.05% the liver of animals getting in addi- tion palm oil decreased in C to 40.9±9.9,with additional sunflowerseed oil to 72.9±14.5mg/g, (p<@.05).Analysis of dietary C by gas chromatography-mass spectrometry revealed none of the k~own toxic oxydation products of C.Hepatic acid lipase activity was the same in stock diet and C fed animals. In accordance with the normal acid lipase activity we found after C feeding a decrease in liver 3-hydroxy-3-methyl-glutarylCoA reductase activity of 90%(p<0.05).Biliary bile acids showing a preponderance of cholie acid were the same in all dietary groups.After C feeding the faecal bile acid excretion increased from 5.5±0.6(SD) to 9.6±0.2~mol/g freeze- dried faeces(p<O.05). We conclude that 1)The underlying mechanism of CE storage in the gerbil seems to be different from human CE storage disease,the former depending partially on DL.2)In view of the high susceptibility for DL and C,the gerbil may be a suitable model for the study of CE metabolism. 3)Based on our findings,because of the risk of interfering liver damage,the gerbil may not be as good a model for C and DL metabolism as has been reported. 278 SERUM AND HEPATIC HEPATITIS B MARKERS IN ALCOHOLIC LIVER DISEASE A.Tom~ Ribeiro, F.T.Veloso, H.Lecour',D.Serr~o",J.V.Saleiro~',F.Pereira Unity of Gastroenterology, "Department of Infectious Diseases, "'Depar- tment of Pathology. Medical School - Hospital S. Jo~o. Porto, Portugal In 22 patients (pts) with alcoholic liver disease we compared HBV markers in serum and in hepatic tissue, and both with histologic and serologic signs of activity of hepatic lesion. Method. HBV serum markers were evaluated by RIA and HBs Ag in the hepatic tissue by indirect IF. In each pt histologic and biochemical activity (ALAT and ASAT and ~ globulin) were classified from 0 to 3. Results. Group I - without HBs Ag in liver tissue: 9 pts, Group II - with weak fluorescence to HBs Ag: 5 pts, Group III- with moderate to strong fluo- rescence to HBs Ag: 8 pts. The prevalence of serum HBs Ag, anti-HBs, anti-HBc, HBe Ag and anti-HBe was not different in the 3 groups. The histologic activi- ty of lesions was higher in Group III than in Group II and in this one higher than in Group I, but these differences were not significant. Chronic active hepatitis was present in 2 pts in Group I, in 1 pt in Group II and in 2 pts in Group III. The values of ALAT and ASAT and ~ globulin were similar in the 3 Groups. Conclusion. We could not find any correlation between HBV markers in serum and hepatic tissue and between both and the activity of the hepatic lesion. $139

Metabolic disorders of the liver after longterm low-dose cholesterol feeding in the mongolian gerbil

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277 METABOLIC DISORDERS OF THE LIVER AFTER LONGTERM LOW-DOSE CHOLESTEROL FEEDING IN THE MONGOLIAN GERBIL.

A.M.Temmerman*,H.J.Houthoff**,R.Vonk*iR.Ber~er*rB.Koopman***rJ.Fernandes*.

* Dept. Paediatrics, University Hospital Groningen, The Netherlands. ** Dept. Pathology, University Groningen. *** Centr. Lab. for Clin. Chem., University Hospital Groningen.

The mongolian gerbil is advocated as a good model for the study of elects of dietary lipids [DL) on cholesterol(C) and lipoprotein metabolism. In order to study long term elects of low dose C,we added 0.2%(w/w) C and/or 8.75% of various DL to their stock diet.In particular ani- mals fed with only C added,died within 2 months.After 4 months liver histology of gerbils fed polyunsaturated fat showed granulomas whereas C fed animals had liver disease varying from severe steatosis and liver cell damage with foam cells to micronodular cirrhosis.On C feeding we observed an increase in hepatic C content of 4±0.5mg/g wet weight up to 107±27mg/g,96% as C ester(CE).2 Months after lowering dietary C to 0.05% the liver of animals getting in addi- tion palm oil decreased in C to 40.9±9.9,with additional sunflowerseed oil to 72.9±14.5mg/g, (p<@.05).Analysis of dietary C by gas chromatography-mass spectrometry revealed none of the k~own toxic oxydation products of C.Hepatic acid lipase activity was the same in stock diet and C fed animals. In accordance with the normal acid lipase activity we found after C feeding a decrease in liver 3-hydroxy-3-methyl-glutarylCoA reductase activity of 90%(p<0.05).Biliary bile acids showing a preponderance of cholie acid were the same in all dietary groups.After C feeding the faecal bile acid excretion increased from 5.5±0.6(SD) to 9.6±0.2~mol/g freeze- dried faeces(p<O.05). We conclude that 1)The underlying mechanism of CE storage in the gerbil seems to be different from human CE storage disease,the former depending partially on DL.2)In view of the high susceptibility for DL and C,the gerbil may be a suitable model for the study of CE metabolism. 3)Based on our findings,because of the risk of interfering liver damage,the gerbil may not be as good a model for C and DL metabolism as has been reported.

278 SERUM AND HEPATIC HEPATITIS B MARKERS IN ALCOHOLIC LIVER DISEASE

A.Tom~ Ribeiro, F.T.Veloso, H.Lecour',D.Serr~o",J.V.Saleiro~',F.Pereira Unity of Gastroenterology, "Department of Infectious Diseases, "'Depar- tment of Pathology. Medical School - Hospital S. Jo~o. Porto, Portugal

In 22 patients (pts) with alcoholic liver disease we compared HBV markers in serum and in hepatic tissue, and both with histologic and serologic signs of activity of hepatic lesion. Method. HBV serum markers were evaluated by RIA and HBs Ag in the hepatic tissue by indirect IF. In each pt histologic and biochemical activity (ALAT and ASAT and ~ globulin) were classified from 0 to 3. Results. Group I - without HBs Ag in liver tissue: 9 pts, Group II - with weak fluorescence to HBs Ag: 5 pts, Group III- with moderate to strong fluo- rescence to HBs Ag: 8 pts. The prevalence of serum HBs Ag, anti-HBs, anti-HBc, HBe Ag and anti-HBe was not different in the 3 groups. The histologic activi- ty of lesions was higher in Group III than in Group II and in this one higher than in Group I, but these differences were not significant. Chronic active hepatitis was present in 2 pts in Group I, in 1 pt in Group II and in 2 pts in Group III. The values of ALAT and ASAT and ~ globulin were similar in the 3 Groups. Conclusion. We could not find any correlation between HBV markers in serum and hepatic tissue and between both and the activity of the hepatic lesion.

$139