Phenylbutyrate exerts adverse effects on liver regeneration and amino acid concentrations in partially hepatectomized rats
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27381898
PubMed Central
PMC4960577
DOI
10.1111/iep.12190
Knihovny.cz E-zdroje
- Klíčová slova
- ammonia, branched-chain amino acids, encephalopathy, glutamine, hepatic injury,
- MeSH
- aminokyseliny metabolismus MeSH
- amoniak metabolismus MeSH
- fenylbutyráty škodlivé účinky MeSH
- glutamin metabolismus MeSH
- hepatektomie metody MeSH
- játra účinky léků metabolismus MeSH
- potkani Wistar MeSH
- regenerace jater účinky léků MeSH
- větvené aminokyseliny účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aminokyseliny MeSH
- amoniak MeSH
- fenylbutyráty MeSH
- glutamin MeSH
- větvené aminokyseliny MeSH
Phenylbutyrate is recommended in urea cycle disorders and liver injury to enhance nitrogen disposal by the urine. However, hypothetically there may be adverse responses to the use of phenylbutyrate in the treatment of liver disease because of its role as a histone deacetylase inhibitor and its stimulatory effect on branched-chain alpha-keto acid dehydrogenase, the rate-limiting enzyme in the catabolism of branched-chain amino acids (BCAA; valine, leucine and isoleucine). We report the effects of phenylbutyrate on liver regeneration and amino acid levels in plasma of partially hepatectomized (PH) rats. Phenylbutyrate or saline was administered at 12-h intervals to PH or laparotomized rats. Phenylbutyrate delayed the onset of liver regeneration compared to the saline-treated controls, as indicated by lower hepatic DNA specific activities 18 and 24( ) h post-PH, decreased hepatic fractional protein synthesis rates 24 h post-PH and lowered the increases in liver weights and hepatic protein and DNA contents 48 h after PH. Hepatic DNA fragmentation (a hallmark of apoptosis) was higher in the phenylbutyrate-treated animals than in controls. Phenylbutyrate decreased the glutamine and BCAA concentrations and the ratio of the BCAA to aromatic amino acids (phenylalanine and tyrosine) in the blood plasma in both hepatectomized and laparotomized animals. In conclusion, the delayed onset of liver regeneration and the decrease in BCAA/AAA ratio in blood suggest that phenylbutyrate administration may be disastrous in subjects with acute hepatic injury and BCAA supplementation is needed when phenylbutyrate is used therapeutically.
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Ben Mosbah I., Alfany‐Fernández I., Martel C. et al (2010) Endoplasmic reticulum stress inhibition protects steatotic and non‐steatotic livers in partial hepatectomy under ischemia‐reperfusion. Cell Death Dis. 1, e52. PubMed PMC
Bolden J.E., Peart M.J. & Johnstone R.W. (2006) Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5, 769–784. PubMed
Brunetti‐Pierri N., Lanpher B., Erez A. et al (2011) Phenylbutyrate therapy for maple syrup urine disease. Hum. Mol. Genet. 20, 631–640. PubMed PMC
Brusilow S.W. (1991) Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion. Pediatr. Res. 29, 147–150. PubMed
Bucher N.L.R. (1967) Experimental aspects of hepatic regeneration. N. Engl. J. Med. 277, 686–696. PubMed
Bucher N.L.R. & Swaffield M.N. (1964) The rate of incorporation of labeled thymidine into the deoxyribonucleic acid of regenerating rat liver in relation to the amount of liver excised. Cancer Res. 24, 1611–1625. PubMed
Burrage L.C., Jain M., Gandolfo L., Lee B.H., Members of the Urea Cycle Disorders Consortium , Nagamani S.C. (2014) Sodium phenylbutyrate decreases plasma branched‐chain amino acids in patients with urea cycle disorders. Mol. Genet. Metab. 113, 131–135. PubMed PMC
Burton K. (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62, 315–323. PubMed PMC
Carducci M.A., Nelson J.B., Chan‐Tack K.M. et al (1996) Phenylbutyrate induces apoptosis in human prostate cancer and is more potent than phenylacetate. Clin. Cancer Res. 2, 379–387. PubMed
Davies N.A., Wright G., Ytrebø L.M. et al (2009) L‐ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats. Hepatology 50, 155–164. PubMed
Enns G.M., Berry S.A., Berry G.T., Rhead W.J., Brusilow S.W. & Hamosh A. (2007) Survival after treatment with phenylacetate and benzoate for urea‐cycle disorders. N. Engl. J. Med. 356, 2282–2292. PubMed
Fischer J.E. & Baldessarini R.J. (1971) False neurotransmitters and hepatic failure. Lancet 2(7715), 75–80. PubMed
Garlick P.J., McNurlan M.A. & Preedy V.R. (1980) A rapid and convenient technique for measuring the rate of protein synthesis in tissue by injection of [3H]phenylalanine. Biochem. J. 192, 719–723. PubMed PMC
Gomes‐Marcondes M.C.C. & Tisdale M.J. (2002) Induction of protein catabolism and the ubiquitin‐proteasome pathway by mild oxidative stress. Cancer Lett. 180, 69–74. PubMed
Higgins G.M. & Anderson R.M. (1931) Experimental pathology of the liver. I. Restoration of liver of white rat following partial surgical removal. Arch. Pathol. 12, 186–202.
Holecek M. (2014) Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy‐therapeutic perspectives. Metab. Brain Dis. 29, 9–17. PubMed PMC
Holecek M. & Kovarik M. (2011) Alterations in protein metabolism and amino acid concentrations in rats fed by a high‐protein (casein‐enriched) diet ‐ effect of starvation. Food Chem. Toxicol. 49, 3336–3342. PubMed
Holecek M., Simek J., Kruf M. & Zadak Z. (1985) Effect of branched chain amino acids on liver regeneration after partial hepatectomy. Physiol. Bohemoslov. 34, 359–366. PubMed
Holecek M., Simek J., Dvorackova I., Subrtova D. & Palicka V. (1986) Spontaneous ingestion of different types of carbohydrates in rats with liver damage and their effect on liver repair. Cs. Gastroenterol. Vyziva 40, 268–275.
Holecek M., Simek J., Palicka V. & Zadak Z. (1991) Effect of glucose and branched chain amino acid (BCAA) infusion on onset of liver regeneration and plasma amino acid pattern in partially hepatectomized rats. J. Hepatol. 13, 14–20. PubMed
Huang J., Barr E. & Rudnick D.A. (2013) Characterization of the regulation and function of zinc‐dependent histone deacetylases during rodent liver regeneration. Hepatology 57, 1742–1751. PubMed PMC
Ke Q., Yang R.N., Ye F. et al (2012) Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice. J. Zhejiang Univ. Sci. B 13, 695–706. PubMed PMC
Koohmaraie M. & Kretchmar D.H. (1990) Comparisons of four methods for quantification of lysosomal cysteine proteinase activities. J. Anim. Sci. 68, 2362–2370. PubMed
Lowry O.H., Rosebrough N.J., Farr A.L. & Randall R.J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275. PubMed
McGuire B.M., Zupanets I.A., Lowe M.E. et al (2010) Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis. Hepatology 51, 2077–2085. PubMed PMC
McNurlan M.A., Tomkins A.M. & Garlick P.J. (1979) The effect of starvation on the rate of protein synthesis in rat liver and small intestine. Biochem. J. 178, 373–379. PubMed PMC
Nair K.S. & Short K.R. (2005) Hormonal and signaling role of branched‐chain amino acids. J. Nutr. 135, 1547S–1552S. PubMed
Rockey D.C., Vierling J.M., Mantry P. et al (2014) Randomized, double‐blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology 59, 1073–1083. PubMed PMC
Scaglia F., Carter S., O'Brien W.E. & Lee B. (2004) Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol. Genet. Metab. 81, S79–S85. PubMed
Welle S. (1999) Methods for studying protein metabolism in humans Welle S, pp. 29–71. New‐York: Human protein metabolism. Springer‐Verlag.
Wilcken B. (2004) Problems in the management of urea cycle disorders. Mol. Genet. Metab. 81, S86–S91. PubMed
Yoshida S., Yunoki T., Aoyagi K. et al (1995) Effect of glutamine supplement and hepatectomy on DNA and protein synthesis in the remnant liver. J. Surg. Res. 59, 475–481. PubMed
Zhang X., Wei L., Yang Y. & Yu Q. (2004) Sodium 4‐phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway. J. Cell. Biochem. 93, 819–829. PubMed