Energy Charge and Mitotic Activity in Regenerating Rat Liver During Parenteral Nutrition

Abstract

The relationship among parenteral nutrition, hepatic energy charge, and mitotic activity was investigated in partially hepatectomized rats fed diets based on glucose, ketone bodies, and saline (starvation). Male Sprague-Dawley rats underwent 70% hepatectomy and jugular vein catheterization for parenteral feeding. All rats were infused with saline for 6 hours, then randomly assigned to one of three parenteral infusions. Rats received either 0.9% saline only (group A rats), 25% glucose + 4% amino acid (group B rats), or 18% monoacetoacetin + 7% glucose + 4% amino acid (group C rats). Three rats receiving saline infusion were killed at 2, 4, and 6 hours after surgery, and three rats from each diet group were killed at 2- to 4-hour intervals from 10 through 32 hours. Hepatic energy charge and mitotic index were measured at each time point. Energy charge was similar for each treatment until 18 hours but was depressed from 6 through 16 hours and began to increase between 16 and 18 hours. Energy charge at 22 hours for group B rats was significantly higher than energy charge for group A and C rats. This difference was maintained through 32 hours. Mitosis started between 24 and 26 hours for all treatments, and group A and C rats exhibited a much higher mitotic index than did group B rats. Adenosine triphosphate was the main driving force for changes in energy charge. The data showed that energy charge and mitotic index were inversely related. It is speculated that high energy charge may negatively influence activity of enzymes inasmuch as activity of these enzymes is altered by phosphorylation-dephosphorylation. (Journal of Parenteral and Enteral Nutrition 18:326–330, 1994)

Get full access to this article

View all access options for this article.

References

1. Birkhahn RH , Awad S , Klaunig JE, et al : Interaction of ketosis and liver regeneration in the rat. J Surg Res 47:427–432, 1989.

2. Caurana JA , Whalen DA , Anthony WP, et al : The paradoxical effects of glucose feeding on liver regeneration and survival after partial hepatectomy. Endocr Res 12:147–151, 1986.

3. Nakatani T , Ozawa K , Asano K, et al : Differences in predominant energy substrate in relation to the resected hepatic mass in the phase immediately after hepatectomy. J Lab Clin Med 97:887, 1981.

4. Bucher NLR , McGowan JA , Russell WE : Control of liver regeneration: Present status. IN Nerve, Organ, and Tissue Regeneration: Research Perspectives, Seil FJ (ed). Academic Press, New York, 1983, pp 455–469

5. Kirsch RE , Frith LO'C , Vinik A, et al : Insulin, glucagon and liver regeneration. S Afr Med J 58:854–856, 1980.

6. Nakatani T , Yasuda K , Ozawa K, et al : Effects of (+)-octanoylearnitine on deoxyribonucleic acid synthesis in regenerating rabbit liver. Clin Sci 62:295–297, 1982.

7. Birkhahn RH , Awad S , Klaunig JE, et al : Effect of parenteral amino acids on DNA synthesis and mitosis in regenerating liver after partial hepatectomy.[Abstr]. JPEN 13(Suppl):22S, 1989.

8. Akerman P , Cote P , Yang SQ, et al : Antibodies to tumor necrosis factor-a inhibit liver regeneration after partial hepatectomy. Am J Physiol 263:G579–G585, 1992.

9. Miles JM , Haymond MW , Gerick JE : Suppression of glucose production and stimulation of insulin secretion by physiological concentrations of ketone bodies in man. J Clin Endocrinol Metab 52:34–37, 1981.

10.

10. Le-Quoc J , Le-Quoc K : Relationships between the NAD(P) redox state, fatty acid oxidation, and inner membrane permeability in rat liver mitochondria. Arch Biochem Biophys 273:466–478, 1989.

11.

11. Lai HS , Chen WJ , Chen KM : Energy substrate for liver regeneration after hepatectomy in rats: Glucose vs fat. JPEN 16:152–156, 1992.

12.

12. Higgins GM , Anderson RM : Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol Lab Med 12:186–202, 1931.

13.

13. Birkhahn RH , Border JR : Intravenous feeding of the rat with short chain fatty acid esters, n. Monoactoacetin. Am J Clin Nutr 31:436–441, 1978.

14.

14. Lamprecht W , Trautschold I : Adenosine-5'-triphosphate: Determination with hexokinase and glucose-6-phosphate dehydrogenase. IN Methods of Enzymatic Analysis, Bergmeyer HU (ed). Academic Press, New York, 1974, pp 2101–2111

15.

15. Jaworek D , Gruber W , Bergmeyer HU : Adenosine-5'-diphosphate and adenosine-5'-monophosphate. IN Methods of Enzymatic Analysis, Bergmeyer HU (ed). Academic Press, New York, 1974, pp 2127–2129.

16.

16. Glantz SA : Primer of Biostatistics, 3rd ed. McGraw-Hill, Inc, New York, 1992, pp 91–94

17.

17. Zajicek G , Schwartz-Arad D , Bartfeld E : The streaming liver V: Time and age-dependent changes of hepatocyte DNA content following partial hepatectomy. Liver 9:164–171, 1989.

18.

18. Melnick RL : Does chemically induced hepatocyte proliferation predict liver carcinogenesis? FASEB J 6:2698–2706, 1992.

19.

19. Atkinson DE : The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 7:4030–4034, 1968.

20.

20. Shen LC , Fall L , Walton GM, et al : Interaction between energy charge and metabolite modulation in the regulation of enzymes of amphibolic sequences: Phosphofructokinase and pyruvate dehydrogenase. Biochemistry 7:4041–4045, 1968.

21.

21. Klungøyr L , Hagemen JH , Fall L, et al : Interaction between energy charge and product feedback in the regulation of biosynthetic enzymes: Aspartokinase, phosphoribosyladenosine triphosphate synthetase, and phosphoribosyl pyrophosphate synthetase. Biochemistry 7:4035–4040, 1968.

22.

22. Sapega AA , Sokolow DP , Graham TJ, et al : Phosphorus nuclear magnetic resonance: A non-invasive technique for the study of muscle bioenergetics during exercise. Med Sci Sports Exerc 19:410–420, 1987.

23.

23. Argov Z , Chance B : Phosphorus magnetic resonance spectroscopy in nutritional research. Ann Rev Nutr 11:449–464, 1991.

24.

24. Rapaport E : Treatment of human tumor cells with ADP or ATP yields arrest of growth in the S phase of the cell cycle. J Cell Physiol 114:279–283, 1983.

25.

25. Rapaport E , Fishman RF , Gercel C : Growth inhibition of human tumor cells in soft-agar cultures by treatment with low levels of adenosine 5'-triphosphate. Cancer Res 43:4402–4406, 1983.

26.

26. Rapaport E : Experimental cancer therapy in mice by adenine nucleotides. Eur J Cancer Clin Oncol 24:1491–1497, 1988.

27.

27. Rapaport E : Mechanisms of anticancer activities of adenine nucleotides in tumor-bearing hosts. Ann NY Acad Sci 603:142–150, 1990.

28.

28. Rathbone MP , Christjanson L , Deforge S, et al : Extracellular purine nucleosides stimulate cell division and morphogenesis: Pathological and physiological implications. Med Hypotheses 37:232–240, 1992.

29.

29. Williamson DH , Lund P , Krebs HA : The redox state of free nicotinamide-adenine dinucleotide in cytoplasm and mitochondria of rat liver. Biochem J 103:514–527, 1967.

30.

30. Reed SI , Dulic V , Lew DJ, et al : Gl control in yeast and animal cells. IN Regulation of the Eukaryotic Cell Cycle, Marsh J (ed). Ciba Foundation 1970, John Wiley, New York, 1992, pp 7–19

31.

31. Dasso M , Smythe C , Milarski K, et al : DNA replication and progression through the cell cycle. IN Regulation of the Eukaryotic Cell Cycle, Marsh J (ed). Ciba Foundation #170, John Wiley, New York, 1992, pp 147–160