The role of polyamines in liver regeneration after hepatectomy with ischemic injury

Ogiso, Seiji; Matsumoto, Takatoshi; Nimura, Yuji

doi:10.1007/bf02385274

Cited by 9 publications

(9 citation statements)

References 26 publications

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“…These results implied that the peak level of SPD beyond the baseline level might be needed to obtain significant effects of polyamines on IRI and regeneration. This finding is supported by other publications reporting that bolus administration of polyamines significantly attenuates injury or promotes regeneration [6, 7, 9, 10]. Additionally, it is also supported by pharmacokinetics/pharmacodynamics theory in pharmacy, which describes the time course of effect intensity in response to administration of an antibiotics dose [17].…”

Section: Discussionsupporting

confidence: 67%

“…Previous reports demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration [5-7]. We also reported that oral polyamine administration by gastric tube alleviates IRI and promotes regeneration in inbred rats [8].…”

Section: Introductionmentioning

confidence: 94%

“…Therefore, in this study, we focused on the influences of administration methods on IRI and regeneration. Previous reports have shown that bolus administration of polyamines significantly attenuates injury or promotes regeneration in rat models [7, 9-12]. We hypothesized that bolus administration of polyamines by gastric tube in a perioperative period will have a greater positive effect on hepatic IRI and regeneration compared with administration by mixed chow.…”

Section: Introductionmentioning

confidence: 95%

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Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats

et al. 2019

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Background:It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. Methods: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 μmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. Results: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. Conclusion: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

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Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats

et al. 2019

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“…21) ODC is known to be involved in cell growth in regenerating liver after partial hepatectomy. [10][11][12] The relationship between TGase and ODC activity must be observed in regenerating liver, since polyamines which are ODC-catalyzed products are good substrates of TGase. Therefore, DNA synthesis in the differential growth capacities between PPH and PVH of regenerating liver may be reciprocally regulated by TGase and ODC.…”

Section: Discussionmentioning

confidence: 99%

“…8) Also, ornithine decarboxylase (ODC; EC 4.1.1.7) is known to be involved in cell growth and its activity increases rapidly and markedly in regenerating liver after partial hepatectomy. [10][11][12] Moreover, endogenous aliphatic polyamines, putrescine (PUT), spermidine (SPD) and spermine (SPM) are produced consequently by ODC from ornithine. PUT, SPD and SPM are also physiological substrates for TGase.…”

mentioning

confidence: 99%

The Involvement of Polyamines as Substrates of Transglutaminase in Zonal Different Hepatocyte Proliferation after Partial Hepatectomy

Ohtake

Suyama

Abe

et al. 2005

Biological & Pharmaceutical Bulletin

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Effect of retinoic acid on transglutaminase and ornithine decarboxylase activities during liver regeneration

Ohtake

Maruko

Ohishi

et al. 2007

Cell Biochemistry & Function

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Liver regeneration is regulated by several factors, including growth factors, cytokines, and post-translational modifications of several proteins. It is suggested that transglutaminase 2 (TG2) and ornithine decarboxylase (ODC) are involved in liver regeneration. To investigate the role of TG2 and ODC activities in regenerating liver, we used retinoic acid (RA), an inducer of TG2 and a suppressor of ODC. Regenerating rat liver was prepared by 70% partial hepatectomy (PH). Rats were sacrificed at 1, 2, 3, 4, and 6 days after surgery. RA was intraperitoneally injected immediately after PH. TG2 and ODC activities and products (epsilon-(gamma-glutamyl) lysine isopeptide (Gln-Lys) and polyamines, respectively) were examined at the indicated times. In RA-treated rat, DNA synthesis and ODC activity declined and the peak shifted to 2 days after PH, whereas TG2 activity increased at 1 day after PH. At that time, protein-polyamine, especially the protein-spermidine (SPD) bond, transiently decreased, whereas the formation of the Gln-Lys bond increased after PH. These results suggested that in regenerating liver, enhanced the formation of Gln-Lys bonds catalyzed by TG2 led to reduced DNA synthesis, whereas when ODC produced newly synthesized SPD, the inhibition of Gln-Lys bond production by the preferential formation of protein-SPD bonds led to an increase in DNA synthesis.

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The role of polyamines in liver regeneration after hepatectomy with ischemic injury

Cited by 9 publications

References 26 publications

Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats

Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats

The Involvement of Polyamines as Substrates of Transglutaminase in Zonal Different Hepatocyte Proliferation after Partial Hepatectomy

Effect of retinoic acid on transglutaminase and ornithine decarboxylase activities during liver regeneration

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