Original Communications| Volume 132, ISSUE 5, P849-856, November 2002

Recovery of liver function in two-third partial hepatectomized rats evaluated by L-[1-13C]phenylalanine breath test


      Background. We have previously reported that by means of a breath test with intravenously administered L-[1-13C] phenylalanine (13Cphe), hepatopathy could be quantitatively evaluated by measuring expiratory 13CO2 levels in a short period. It is known that phenylalanine hydroxylase activity (PAHA) plays an important role in phenylalanine metabolism. We examined the relationship between changes in PAHA and the results of the 13Cphe breath test during hepatic regeneration in a rat model of 70% hepatectomy, to assess their usefulness for evaluating hepatic regeneration. Methods. Male Wistar rats (Shizvoka Laboratory Animal Center, Hamamatsu, Japan) weighing 230 to 290 g were subjected to 70% hepatectomy under anesthesia with sodium pentobarbital. One, 2, 3, 5, 7, and 14 days postoperatively, 30 mg/kg 13Cphe was intravenously injected into the femoral vein, and the increase in exhaled 13CO213CO2) was measured for 15 minutes. Simple laparotomy was performed in control rats. After the breath test, the regenerated liver was removed and weighed. The amount of DNA, amount of hepatic tissue total protein (TP), and PAHA were determined. Results. The r between liver weight/body weight and PAHA, between DNA and PAHA, and between TP and PAHA were 0.832, 0.720, and 0.758, respectively. Breath test graphs revealed that liver weight/body weight, DNA, and TP showed the best correlations with the peak value of Δ13CO2 (liver weight/body weight percentage, r = 0.801; DNA, r = 0.660; TP, r = 0.706), and r between PAHA and peak value was 0.638. Conclusions. These results suggest that measurement of PAHA in regenerated liver is an effective method for following up liver function after hepatic resection. Moreover, the 13Cphe breath test may also be useful to evaluate liver function after partial hepatectomy. Surgery 2002;132:849-56.
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        • Wolf HK
        • Michalopoulos GK.
        Hepatocyte regeneration in acute fulminant and nonfulminant hepatitis: a study of proliferating cell nuclear antigen expression.
        Hepatology. 1992; 15: 707-713
        • MacDermott KJ
        • Weber AL.
        Major hepatic resection: diagnostic techniques and metabolic problems.
        Surgery. 1963; 54: 56-66
        • Parker JJ
        • Siemsen JK.
        Liver regeneration following hepatectomy, evaluated by scintillation scanning.
        Radiology. 1967; 88: 342-344
        • Barrett Jr, O
        • Cohen A.
        Liver regeneration after major hepatectomy: effect of chemotherapy on growth and function, case report.
        Cancer. 1968; 22: 268-273
        • Aronsen KF
        • Ericsson B
        • Nosslin B
        • Nylander G
        • Pihl B
        • Waldeskog B.
        Evaluation of hepatic regeneration by scintillation scanning, cholangiography and angiography in man.
        Ann Surg. 1970; 171: 567-574
        • Heymsfield SB
        • Fulenwider T
        • Nordlinger B
        • Barlow R
        • Sones P
        • Kutner M.
        Accurate measurement of liver, kidney and spleen volume and mass by computerized axial tomography.
        Ann Intern Med. 1979; 90: 185-187
        • Chen MF
        • Hwang TL
        • Hung CF
        Human liver regeneration after major hepatectomy: astudy of liver volume by computed tomography [see comments].
        Ann Surg. 1991; 213: 227-229
        • Okamoto E
        • Kyo A
        • Yamanaka N
        • Tanaka N
        • Kuwata K.
        Prediction of the safe limit of hepatectomy by combined volumetric and functional measurements.
        Surgery. 1984; 95: 586-591
        • Hepner GW
        • Vesell ES.
        Assessment of aminopyrine metabolism in man by breath analysis after oral administration of 14C-aminopyrine. Effects of phenobarbital, disulfiram and portal cirrhosis.
        N Engl J Med. 1974; 291: 1384-1388
        • Schneider JF
        • Schoeller DA
        • Nemchausky B
        • Boyer JL
        • Klein P.
        Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labeled aminopyrine in man.
        Clin Chim Acta. 1978; 84: 153-162
        • Breen KJ
        • Bury RW
        • Calder IV
        • Desmond PV
        • Peters M
        • Mashford ML
        A [14C]phenacetin breath test to measure hepatic function in man.
        Hepatology. 1984; 4: 47-52
        • Matsumoto K
        • Suehiro M
        • Iio M
        • Kawabe T
        • Shiratori Y
        • Okano K
        • et al.
        [13C]methacetin breath test for evaluation of liver damage.
        Dig Dis Sci. 1987; 32: 344-348
        • Renner E
        • Wietholtz H
        • Huguenin P
        • Arnaud MJ
        • Preisig R.
        Caffeine: a model compound for measuring liver function.
        Hepatology. 1984; 4: 38-46
        • Oellerich M
        • Raude E
        • Burdelski M
        • Schulz M
        • Schmidt FW
        • Ringe B
        • et al.
        Monoethylglycinexylidide formation kinetics: a novel approach to assessment of liver function.
        J Clin Chem Clin Biochem. 1987; 25: 845-853
        • Hunton DB
        • Bollman JL
        • Hoffman HN.
        The plasma removal of indocyanine green and sulfobromophthalein: effect of dosage and blocking agents.
        J Clin Invest. 1961; 40: 1648-1658
        • Rosenthal SM
        • White EC.
        Studies in hepatic function: the pharmacological behavior of certain phthalein dyes; the value of selected phthalein compounds in the estimations of hepatic function.
        J Pharmacol Exp Ther. 1924; 24: 265-272
        • Jost G
        • Wahllander A
        • von Mandac U
        • Preisig R.
        Overnight salivary caffeine clearance: a liver function test suitable for routine use.
        Hepatology. 1987; 7: 338-344
        • Henderson JM
        • Kutner MH
        • Bain RP.
        First order clearance of plasma galactose: the effect of liver disease.
        Gastroenterology. 1982; 83: 1090-1096
        • Mion F
        • Rousseau M
        • Scoazec JY
        • Berger F
        • Minaire Y
        [13C]-Galactose breath test: correlation with liver fibrosis in chronic hepatitis C.
        Eur J Clin Invest. 1999; 29: 624-629
        • Heberer M
        • Talke H
        • Maier KP
        • Gerok W.
        Metabolism of phenylalanine in liver diseases.
        Klin Wochenschr. 1980; 58: 1189-1196
        • Clowes Jr, GJ
        • McDermott WV
        • Williams LF
        • Loda M
        • Menzoian JO
        • Pearl R.
        Amino acid clearance and prognosis in surgical patients with cirrhosis.
        Surgery. 1984; 96: 675-685
        • Pearl RH
        • Clowes GH
        • Bosari S
        • McDermott WV
        • Menzoian JO
        • Love W
        • et al.
        Amino acid clearance in cirrhosis: a predictor of postoperative morbidity and mortality.
        Arch Surg. 1987; 122: 468-473
        • Burke PA
        • Stack JA
        • Wagner D
        • Lewis DW
        • Jenkins RL
        • Forse RA
        L-[1-13C] phenylalanine oxidation as a measure of hepatocyte functional capacity in end-stage liver disease.
        Am J Surg. 1997; 173: 270-273
        • Ishii Y
        • Asai S
        • Kohno T
        • Suzuki S
        • Ishii M
        • Hosoi I
        • et al.
        13CO2 peak value of L-[1-13C]phenylalanine breath test reflects hepatopathy.
        J Surg Res. 1999; 86: 130-135
        • Higgins GM
        • Anderson RM.
        Experimental pathology of liver: restoration of liver of the white rat following partial surgical removal.
        Arch Pathol. 1931; 12: 186-202
        • Galand P
        • Degraef C.
        Cyclin/PCNA immunostaining as an alternative to tritiated thymidine pulse labelling for marking S phase cells in paraffin sections from animal and human tissues.
        Cell Tissue Kinet. 1989; 22: 383-392
        • Karsten U
        • Wollenberger A.
        Determination of DNA and RNA in homogenized cells and tissues by surface fluorometry.
        Anal Biochem. 1972; 46: 135-148
        • Yildirim SI
        • Poulsen HE.
        Quantitative liver functions after 70% hepatectomy.
        Eur J Clin Invest. 1981; 11: 469-472
        • Sendama I
        • Hemptinne B
        • Lambotte L.
        Recovery of liver function in partially hepatectomized rats evaluated by aminopyrine demethylation capacity.
        Hepatology. 1985; 5: 629-633
        • Hashimoto M
        • Sanjo K.
        Fuctional capacity of the liver after two-thirds partial hepatectomy in the rat.
        Surgery. 1997; 121: 690-697
        • Poulsen HE
        • Pilsgaard H.
        Antipyrine metabolism during hepatic regeneration in the rat.
        Liver. 1985; 5: 196-199
        • Assy N
        • Minuk GY.
        Liver regeneration: methods for monitoring and their applications.
        J Hepatol. 1997; 26: 945-952
        • Bucher NLR.
        Regeneration of mammalian liver.
        Int Rev Cytol. 1963; 15: 245-300
        • Bravo R
        • Rainer F
        • Blundel PA
        • Macdonald BH.
        Cyclin/PCNA is the auxiliary protein of DNA polymerase delta.
        Nature. 1987; 326: 515-517
        • Manjunath R
        • Shivaswamy V
        • Ramasarma T.
        Decrease of phenylalanine hydroxylase during hepatocyte proliferation.
        Biochem Pharmacol. 1982; 15: 1521-1525
        • Kaufman S
        The phenylalaninne hydroxylating system from mammalian liver.
        Adv Enzymol Relat Areas Mol Biol. 1971; 35: 245-319
        • Lichter-Konecki U
        • Hipke CM
        • Konecki DS.
        Human phenylalanine hydroxylase gene expression in kidney and other nonhepatic tissues.
        Mol Genet Metab. 1999; 67: 308-316