alcohol-induced liver injury following jejunoileal bypass (jip) in rats: changes in hepatic contents...

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180 ALCOHOL-INDUCED LIVER INJURY FOLLOWINGJEJUNOILEAL BYPASS (JIP) IN RATS: CHANGES IN HEPATIC CONTENTSOF CARNITIN; COENZYMEA (CoA) AND THEIR ACYLESTERS Ch. Bode, B. Brauner, J.Ch. Bode Department of Internal Medicine, Robert-Bosch-Krankenhaus, Stuttgart, F.R.G. In a recent study we could demonstrate that alcohol-feeding (AF) in rats with JIB leads to marked fatty liver and other signs of liver injury (2nd ISBRA Meeting, Helsinki, June 1986). The aim of the present study was to clarify whether changes in the hepatic content of carnitin (Carn.), CoA and their acylesters occur in this model of alcoholic liver injury. Material and methods: Male Wistar rats (SPF) were subjected I) to a 90 % JIB or 2) to a sham-operation (SO). Groups (n=6-7) of JIB and SO were fed a) a liquid diet with 36 % of alcohol (AD) or b) a diet were alcohol was replaced isocalorically by starch (CD, pair-feeding). After 4 months the liver was removed in ether anesthesia for extraction and estimation of free CoA, free Carn. and their acetyl-(Ac) and acylesters (short-chain=Sc,long-chain=Lc). Results: I) AF in SO did not significantly influence the content of free CoA, free Carn. ~ r Ac- or acylester. 2) In the liver of animals with JIB receiving CD Carn. and its Sc-esters decreased significantly when compared to SO (free -45%, Ac -40%, Sc -47%, pc 0.05 respectively) while LC-esters increased (+16%, n.s.). A less pronounced decrease was observed for free CoA (-20%), Ac-CoA (-20%) and Lc-CoA (-26%, p< 0.05 respectively). 3) AF in JIB resulted in a further decrease in free Carn.(-33%, p 0.05) and an increase in Ac-Carn. (+80%, p<0.05). Conclusion: The decrease in hepatic free Carn. and CoA and their Ac-esters might play a role in the fatty liver induced by AD after JIB. 181 ALCOHOL-INDUCED LIVER INJURY FOLLOWING JEJUNOILEAL BYPASS OPERATION (JIB) IN RATS: EFFECT ON ADENOSINPHOSPHATES AND PHOSPHOLIPIDS J.Ch. Bode, B. Brauner, Ch. Bode Department of Internal Medicine, Robert- Bosch-Krankenhaus, Stuttgart, F.R.G. Ina recent study we could demonstrate that alcDhol-feeding in rats with JIB leads to marked fatty liver and other signs of liver injury (2nd ISBRA Meeting, Helsinki, June 1986). The aim of the present study was to investigate whether changes in the contents of adenosinphsphates (AP) and phospholipids (PL) might contribute to the development of this type of experimental alcoholic liver injury. Material and methods: Male Wistar rats (SPF) were subjected I) to a 90% JIB or 2) to a sham-operation (SO). Groups (n=6-7) of JIB and SO were fed a) a liquid diet with 36 % alcohol (AD) or b) a diet were alcohol was replaced isocalorically by starch (CD, pair-feeding). After 4 months a sample of the liver was removed by freeze-clamp technique for estimation of ATP, ADP and AMP in light ether anesthesia. Other samples were taken for determination of triglycerides (T), PL and liver histology. Results: I) Feeding AD in JIB caused a marked fat accumulation (histology + T content). In rats with JIB receiving CD ATP decreased by 40% when compared to SO (p<O.O5). Feeding AD in rats with JIB lead to a further reduction in ATP (-41%,p~0.05). Total content of AP was markedly reduced by AD when compared to CD in rats with JIB (-40%, pc0.05). 3) Feeding AD resulted in a decrease in total PL content in rats with JIB (pc 0.05) while the content of lecithin was only slightly reduced (n.s.). Conclusion: The results support the assumption of a decreased energy supply as one possible causative factor in the pathogenesis of alcoholic liver injury following JIB. $96

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180 ALCOHOL-INDUCED LIVER INJURY FOLLOWING JEJUNOILEAL BYPASS (JIP) IN RATS: CHANGES IN HEPATIC CONTENTS OF CARNITIN; COENZYME A (CoA) AND THEIR ACYLESTERS Ch. Bode, B. Brauner, J.Ch. Bode Department of Internal Medicine, Robert-Bosch-Krankenhaus, Stuttgart, F.R.G.

In a recent study we could demonstrate that alcohol-feeding (AF) in rats with JIB leads to marked fatty l iver and other signs of l iver injury (2nd ISBRA Meeting, Helsinki, June 1986). The aim of the present study was to c la r i fy whether changes in the hepatic content of carnit in (Carn.), CoA and their acylesters occur in this model of alcoholic l iver injury. Material and methods: Male Wistar rats (SPF) were subjected I) to a 90 % JIB or 2) to a sham-operation (SO). Groups (n=6-7) of JIB and SO were fed a) a l iquid diet with 36 % of alcohol (AD) or b) a diet were alcohol was replaced isocalorical ly by starch (CD, pair-feeding). After 4 months the l iver was removed in ether anesthesia for extraction and estimation of free CoA, free Carn. and their acetyl-(Ac) and acylesters (short-chain=Sc,long-chain=Lc).

Results: I) AF in SO did not s igni f icant ly influence the content of free CoA, free Carn. ~ r Ac- or acylester. 2) In the l iver of animals with JIB receiving CD Carn. and i ts Sc-esters decreased s igni f icant ly when compared to SO (free -45%, Ac -40%, Sc -47%, pc 0.05 respectively) while LC-esters increased (+16%, n.s.) . A less pronounced decrease was observed for free CoA (-20%), Ac-CoA (-20%) and Lc-CoA (-26%, p< 0.05 respectively). 3) AF in JIB resulted in a further decrease in free Carn.(-33%, p 0.05) and an increase in Ac-Carn. (+80%, p<0.05).

Conclusion: The decrease in hepatic free Carn. and CoA and their Ac-esters might play a role in the fat ty l iver induced by AD after JIB.

181 ALCOHOL-INDUCED LIVER INJURY FOLLOWING JEJUNOILEAL BYPASS OPERATION (JIB) IN RATS: EFFECT ON ADENOSINPHOSPHATES AND PHOSPHOLIPIDS J.Ch. Bode, B. Brauner, Ch. Bode Department of In ternal Medicine, Robert- Bosch-Krankenhaus, Stu t tgar t , F.R.G.

Ina recent study we could demonstrate that alcDhol-feeding in rats with JIB leads to marked f a t t y l i v e r and other signs of l i v e r in ju ry (2nd ISBRA Meeting, Hels ink i , June 1986). The aim of the present study was to invest igate whether changes in the contents of adenosinphsphates (AP) and phospholipids (PL) might contr ibute to the development of t h i s type of experimental a lcohol ic l i v e r in ju ry .

Material and methods: Male Wistar rats (SPF) were subjected I) to a 90% JIB or 2) to a sham-operation (SO). Groups (n=6-7) of JIB and SO were fed a) a l i qu id d ie t wi th 36 % alcohol (AD) or b) a d ie t were alcohol was replaced i soca lo r i ca l l y by starch (CD, pa i r - feeding) . Af ter 4 months a sample of the l i v e r was removed by freeze-clamp technique for estimation of ATP, ADP and AMP in l i g h t ether anesthesia. Other samples were taken fo r determination of t r i g l yce r i des (T), PL and l i v e r h is to logy.

Results: I) Feeding AD in JIB caused a marked fa t accumulation (h is to logy + T content) . In rats with JIB receiving CD ATP decreased by 40% when compared to SO (p<O.O5). Feeding AD in rats with JIB lead to a fu r the r reduction in ATP (-41%,p~0.05). Total content of AP was markedly reduced by AD when compared to CD in rats with JIB (-40%, pc0 .05) . 3) Feeding AD resulted in a decrease in to ta l PL content in rats with JIB (pc 0.05) whi le the content of l ec i t h i n was only s l i g h t l y reduced (n .s . ) .

Conclusion: The resul ts support the assumption of a decreased energy supply as one possible causative factor in the pathogenesis of a lcohol ic l i v e r in ju ry fo l lowing JIB.

$96