Biochemistry and Functions of the Liver

Kuntz, E; Kuntz, Hans-Dieter

doi:10.1007/978-3-662-04680-7_3

Cited by 27 publications

(11 citation statements)

References 140 publications

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“…This study uses primary human hepatocytes, which are typically cultured in monolayers and suspensions. We first used immunohistochemistry to characterize the spheroids for albumin, a marker of liver function used extensively in the clinic, and multidrug resistance-associated protein (MRP2), an apical membrane protein responsible for the Phase III transport of conjugated xenobiotics into the bile canaliculi [49]. After first characterizing hepatocyte spheroids, we looked at CYP induction/inhibition and viability in response to known inducers and inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction

Desai

Tseng

Souza

2017

IJMS

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There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces. With this platform, spheroids can be rapidly assembled and easily handled, while replicating native liver function. We assembled spheroids of primary human hepatocytes in a 384-well format and maintained this culture over five days, including a 72 h induction period with known CYP450 inducers/inhibitors. CYP450 activity and viability in the spheroids were assessed and compared in parallel with monolayers. CYP450 activity was induced/inhibited in spheroids as expected, separate from any toxic response. Spheroids showed a significantly higher baseline level of CYP450 activity and induction over monolayers. Positive staining in spheroids for albumin and multidrug resistance-associated protein (MRP2) indicates the preservation of hepatocyte function within spheroids. The study presents a proof-of-concept for the use of magnetic 3D cell culture for the assembly and handling of novel hepatic tissue models.

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Section: Introductionmentioning

confidence: 99%

Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction

Desai

Tseng

Souza

2017

IJMS

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“…The liver is the largest organ in the body and plays an essential role in the regulation of energy homeostasis, synthesis of most secreted proteins in the blood, excretion of bile acids required for lipid absorption, and elimination of extrinsic or intrinsic toxic substances (Kuntz and Kuntz, 2008). Impairment of liver function leads to liver failure, which is a fatal condition if not treated properly.…”

Section: Introductionmentioning

confidence: 99%

Antioxidative, antiapoptotic, and proliferative effect of curcumin on liver regeneration after partial hepatectomy in rats

et al. 2013

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The aim of the present study was to assess the influence of curcumin on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Sprague Dawley rats were divided into three groups: sham-operated (SH), PH, and PH + curcumin; each group contains eight animals. The rats in curcumin-treated groups were given curcumin (in a dose of 100 mg/kg body weight) once a day orally for 7 days, starting 3 days prior to hepatectomy operation. At 7 days after resection, liver samples were collected. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labeling, proliferation index (PI), transferase-mediated 2'-deoxyuridine, 5'-triphosphate nick end-labeling assay, and apoptotic index (AI) were evaluated at 7 days after hepatectomy. As a result, curcumin significantly increased MI and PI and significantly decreased AI in PH rats. Additionally, curcumin remarkably inhibited MDA elevation, restored impaired antioxidant SOD activity and GSH level and also attenuated hepatic vacuolar degeneration and sinusoidal congestion. These results suggested that curcumin treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic, and proliferative properties.

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“…Através de um sistema enzimático oxidante sua estrutura é transformada em linear originando a biliverdina que possui coloração verde. A biliverdina por sua vez é reduzida à bilirrubina, a qual possui coloração amarelada (Chowdhuryet al, 2007;Kuntz;Kuntz, 2006b;Guyton;Hall, 2011).…”

Section: Bilirrubinaunclassified

“…Os ácidos biliares secundários tornam-se parcialmente absorvidos no intestino e, após reconjugação com glicina ou taurina no fígado, são excretados para o canalículo. A bile contém, portanto, uma mistura de ácidos biliares primários e secundários (Kuntz;Kuntz, 2006c). Os ácidos biliares terciários (sulfolitocólico e ursodesoxicólico) são formadas no fígado e intestino, e são derivados a partir dos ácidos biliares secundários que passam pela circulação ênterohepática, formando uma nova estrutura química (Kuntz;Kuntz, 2006c).…”

Section: Sais Biliaresunclassified

“…A bile contém, portanto, uma mistura de ácidos biliares primários e secundários (Kuntz;Kuntz, 2006c). Os ácidos biliares terciários (sulfolitocólico e ursodesoxicólico) são formadas no fígado e intestino, e são derivados a partir dos ácidos biliares secundários que passam pela circulação ênterohepática, formando uma nova estrutura química (Kuntz;Kuntz, 2006c). A síntese de ácido biliar e fluxo biliar diminui acentuadamente durante o envelhecimento (Bertolotti et al, 2007) e que os ácidos biliares e seus receptores são alvos terapêuticos para o desenvolvimento de drogas no tratamento de doenças esteatohepáticas e colestáticas, diabetes, obesidade e síndrome metabólica (Chiang, 2009).…”

Section: Sais Biliaresunclassified

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