Biochemistry and regulation of liver regeneration

Malik, Salman A (1983) Biochemistry and regulation of liver regeneration. PhD thesis, University of Glasgow.

Abstract

1. Attempts have been made to use clearance of bromsulphalein or of alcohol to estimate the growth of the liver fragment after partial hepatectomy. 2. The liver's ability to clear an injected dose of bromsulphalein is not affected by biopsy but is diminished to about 45 per cent of the control value after partial hepatectomy. A similar reduction is produced by fasting or induction of diabetes by administration of alloxan. 3. The liver's ability to clear an injected dose of ethanol is not affected by biopsy but is reduced to almost zero fifteen minutes after partial hepatectomy. 4. A comparison has been made of the composition and metabolism of the liver remaining after either two-thirds hepatectomy or removal of a small biopsy. 5. The wet weight, dry weight and total protein content of the remaining liver fragment show no change for the first twelve hours after partial hepatectomy. Thereafter they increase together at a rate which remains roughly constant for the next twenty-four hours. DNA synthesis, measured by [3H]-thymidine incorporation, starts to increase sixteen hours after the operation, reaches a peak at twenty-four hours and thereafter declines sharply. The total DNA content of the liver fragment remains unaltered for sixteen hours after the operation but thereafter increases steadily for the next twenty hours. 6. The mean cell mass (wet and dry) and the protein content per cell fall slightly in the first four hours after partial hepatectomy then rise to a maximum at about twelve hours, returning to the pre-operative level at twenty hours. Biopsy produces similar but less marked changes. 7. Both partial hepatectomy and liver biopsy result in a precipitate loss of glycogen from the remaining liver cells followed by a slow recovery. The loss is slightly greater, and the recovery slightly slower, after partial hepatectomy. The lipid content per cell increases markedly after partial hepatectomy and the RNA per cell falls. Neither of these is affected by removal of a biopsy. 8. In the anaesthetized laparatomized rat the liver secretes glucose and lipids into the blood flowing through it. At the same time it takes up phospholipids, proteins, ammonia and oxygen. 9. The immediate effects of biopsy are to increase glucose output, change output of lipids to rapid uptake, decrease the uptake of proteins and increase, the uptake of oxygen by the liver. There is no effect on the uptake of ammonia and phospholipids. These changes however are soon reversed/,and by eight to twelve hours the uptake and release of metabolites by the liver is much as it was before the operation. 10. The effects of partial hepatectomy differ from those of biopsy in the following respects. a) The output of glucose decreases instead of increasing and after returning to normal between eight to twelve hours it decreases again. b) The uptake of lipids is significantly less but the return to normal is much slower. c) The uptake of phospholipids is less. d) The uptake of proteins (after the initial decrease at four hours) is very much greater. e) The uptake of ammonia shows erratic changes; but there is a steady increase in the ammonia concentration in the hepatic venous blood. f) The uptake of oxygen by the liver fragment is as great as that of the liver after biopsy, in spite of the fact that the liver fragment amounts to only one third of the intact organ. 11. The consumption of oxygen vitro by liver slices has been measured. Slices from the fragment remaining after partial hepatectomy show a substantially greater uptake than slices from normal liver. The uptake is maximal (twice normal) at sixteen hours and thereafter starts to decline. Slices from a liver from which a biopsy has been taken show only a small increase in uptake at four hours and thereafter return to normal. 12. If partial hepatectomy is performed on a fasted rat,jthe increase in lipid concentration in the liver and the peak of DNA synthesis occur about eight hours later than is the case if the operation is performed on a fed animal. 13. The response to partial hepatectomy, in terms of increase in liver remnant weight, increase in lipid concentration and increase in rate of DNA synthesis is not modified if the time of day at which the operation is carried out is varied. 14. Intraperitoneal injections of a commercial amino-acid mixture supplemented with glucose into rats produce a small decrease in the mean cell mass and the content of RNA per cell in the liver. 15. Partial hepatectomy performed on rats made diabetic by previous administration of alloxan is followed by liver regeneration comparable, in terms of increase in liver mass and DNA content, to that elicited in healthy animals. 16. A single intraperitoneal injection of indomethacin four hours before partial hepatectomy results in a delay of the peak of DNA synthesis and a reduction in the increase of liver remnant weight. Multiple injections of indomethacin effectively inhibit both.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: R Y Thomson
• Keywords: Biochemistry
• Date of Award: 1983
• Depositing User: Enlighten Team
• Unique ID: glathesis:1983-73355
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73355