Alterations in hepatic lobar function in regenerating rat liver

Fülöp, András; Budai, András; Czigány, Zoltán; Lotz, Gábor; Dezső, Katalin; Paku, Sándor; Harsányi, László; Szíjártó, Attila

doi:10.1016/j.jss.2015.04.033

Cited by 5 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, the individual drug metabolism of the NLL seems to be re-established, whereas permanently deteriorated in the LL, confirming disparate tendencies of adaption, and a shift of hepatic drug metabolism towards the NLL. These are in accordance with the latest studies of our workgroup, involving complex liver functional analyses following PVL [20, 31]. Concerning clinical significance, the present results may help characterize liver functional changes during two-step liver resections incorporating future liver remnant enlargement via PVO procedures, translating as the enhanced itineration of the second-step resection.…”

Section: Discussionsupporting

confidence: 90%

“…In accordance with this, Takemura et al [30] and Starkel et al [33] also found a transient reduction in hepatic drug metabolism following PVL. Furthermore, on a larger scale, the transitional deterioration of global liver function after PVO, as confirmed by different functional tests, was described both by our and other previous literature reports [20, 31, 34]. On the other hand, the sleeping test fails to assess the individual functional aspects of the LL and the NLL.…”

Section: Discussionsupporting

confidence: 57%

“…Eventually, the LL undergoes atrophy and underlying necroapoptotic cell death, meanwhile the NLL displays an intensive cellular proliferation and hypertrophy [21, 29], which was repeatedly proven by the literature [2, 5, 29, 30] and previous reports of our workgroup [20, 21, 31]. In the present study, it was similarly reflected by liver lobe weights, thereby validating the standard application of the PVL model, and allowing further, more sophisticated analysis.…”

Section: Discussionmentioning

confidence: 57%

“…Beyond the seemingly solitary action of portal blood flow stoppage to the LL, PVL induces a chain of events, such as the complete redistribution of the splanchnic circulation (arterialized hypoperfusion of the LL; massive portal hyperperfusion of the NLL) and modification of blood decomposition, by which the NLL receives an increased portion of nutritional agents, growth factors, hormones, and bacterial products [29]. These culminate in the induction of a very special form of liver regeneration characterized by the atrophy-hypertrophy complex [29, 35], and diverse pathophysiological changes of structural and microvascular remodeling within the LL and the NLL [20, 29], which may ultimately explain the different functional capacities of the LL and the NLL [31, 35]. The other important finding that should be addressed is the markedly different pattern of changes regarding the CYP2C enzymes as compared to CYP1A, CYP2B, and CYP3A.…”

Section: Discussionmentioning

confidence: 99%

“…injection of 75 mg/body weight [bw] kg ketamine and 7.5 mg/bw kg xylazine in 1.5 mL saline), rats underwent median laparotomy and PVL affecting approximately 80% of the total liver parenchyma ( n = 20), as previously described by our workgroup [20, 21]. After abdominal saline lavage, antibiotic (10 mg/bw kg metronidazol i.p.)…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Surgical removal of complicated liver tumors may be realized in two stages via selective portal vein ligation, inducing the atrophy of portally ligated lobes and the compensatory hypertrophy of nonligated liver lobes. Unlike morphological changes, functional aspects such as hepatic cytochrome P450 (CYP)-mediated drug metabolism remain vaguely understood, despite its critical role in both drug biotransformation and hepatic functional analysis. Our goal was the multilevel characterization of hepatic CYP-mediated drug metabolism after portal vein ligation in the rat. Methods: Male Wistar rats (n = 24, 210–230 g) were analyzed either untreated (controls; n = 4) or 24/48/72/168/336 h (n = 4 each) following portal vein ligation affecting approximately 80% of the liver parenchyma. Besides the weights of ligated and nonligated lobes, pentobarbital (30 mg/kg)-induced sleeping time, CYP1A(2), CYP 2B(1/2), CYP2C(6/11/13), CYP3A(1) enzyme activities, and corresponding isoform mRNA expressions, as well as CYP3A1 protein expression were determined by in vivo sleeping test, CYP isoform-selective assays, polymerase chain reaction, and immunohistochemistry, respectively. Results: Portal vein ligation triggered atrophy in ligated lobes and hypertrophy nonligated lobes. Sleeping time was transiently elevated (p = 0.0451). After an initial rise, CYP1A, CYP2B, and CYP3A enzyme activities dropped until 72 h, followed by a potent increase only in the nonligated lobes, paralleled by an early (24–48 h) transcriptional activation only in nonligated lobes. CYP2C enzyme activities and mRNA levels were bilaterally rapidly decreased, showing a late reconvergence only in nonligated lobes. CYP3A1 immunohistochemistry indicated substantial differences in positivity in the early period. Conclusions: Beyond the atrophy-hypertrophy complex, portal vein ligation generated a transient suppression of global and regional drug metabolism, re-established by an adaptive, CYP isoform-dependent transcriptional response of the nonligated lobes.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

Comparable liver function and volume increase after portal vein embolization in rabbits and humans

Olthof

Heger

Lienden

et al. 2017

Surgery

View full text Add to dashboard Cite

Functional shift with maintained regenerative potential following portal vein ligation

Kovács

Máthé

Fülöp

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Selective portal vein ligation (PVL) allows the two-stage surgical resection of primarily unresectable liver tumours by generating the atrophy and hypertrophy of portally ligated (LL) and non-ligated lobes (NLL), respectively. To evaluate critically important underlying functional alterations, present study characterised in vitro and vivo liver function in male Wistar rats (n = 106; 210–250 g) before, and 24/48/72/168/336 h after PVL. Lobe weights and volumes by magnetic resonance imaging confirmed the atrophy-hypertrophy complex. Proper expression and localization of key liver transporters (Ntcp, Bsep) and tight junction protein ZO-1 in isolated hepatocytes demonstrated constantly present viable and well-polarised cells in both lobes. In vitro taurocholate and bilirubin transport, as well as in vivo immunohistochemical Ntcp and Mrp2 expressions were bilaterally temporarily diminished, whereas LL and NLL structural acinar changes were divergent. In vivo bile and bilirubin-glucuronide excretion mirrored macroscopic changes, whereas serum bilirubin levels remained unaffected. In vivo functional imaging (indocyanine-green clearance test; 99mTc-mebrofenin hepatobiliary scintigraphy; confocal laser endomicroscopy) indicated transitionally reduced global liver uptake and -excretion. While LL functional involution was permanent, NLL uptake and excretory functions recovered excessively. Following PVL, functioning cells remain even in LL. Despite extensive bilateral morpho-functional changes, NLL functional increment restores temporary declined transport functions, emphasising liver functional assessment.

show abstract

Alterations in hepatic lobar function in regenerating rat liver

Cited by 5 publications

References 32 publications

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat

Comparable liver function and volume increase after portal vein embolization in rabbits and humans

Functional shift with maintained regenerative potential following portal vein ligation

Contact Info

Product

Resources

About