Coordinated cytochrome P450 expression in mouse liver and intestine under different dietary conditions during liver regeneration after partial hepatectomy

Fujino, Chieri; Sanoh, Seigo; Tateno, Chise; Ohta, Shigeru; Kotake, Yaichiro

doi:10.1016/j.taap.2019.03.010

Cited by 7 publications

(12 citation statements)

References 53 publications

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“…The results of our study are consistent with these facts. In our study, all animals included achieved and exceeded their baseline body weight by the completion of the study ( Fig 3 ); these findings are consistent with those reported by Fujino et al in a similar mice model [ 24 ]. In addition, evaluation of liver weight (data available in the online repository) demonstrated that all residual liver lobes harvested had regained the initial organ weight on POD7.…”

Section: Discussionsupporting

confidence: 92%

“…During this period, the focus is on restoring the original organ size and function. In rodents, this healing process takes 7–10 days on average, depending on the amount of tissue resected [ 19 , 21 , 24 ]. The results of our study are consistent with these facts.…”

Section: Discussionmentioning

confidence: 99%

“…Within the first three days after liver resection, the organism responds to tissue loss [19,[22][23][24]. During this period, the focus is on restoring the original organ size and function.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, evaluation of liver weight (data available in the online repository) demonstrated that all residual liver lobes harvested had regained the initial organ weight on POD7. The surgical procedure and the tissue loss affect the body weight of the animal and blood parameters [24,25] in addition to causing wound pain [26][27][28][29]. While surgical interventions can lead to inflammation and thus to changes in the white blood cell counts, bleeding ; no significant differences between treatments were found.…”

Section: Discussionmentioning

confidence: 99%

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Assessing the severity of laparotomy and partial hepatectomy in male rats—A multimodal approach

et al. 2021

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This study assessed the postoperative severity after three different visceral surgical interventions in rats by using objective parameters pertaining to various disciplines. The objective was to evaluate whether the degree of severity increases with the invasiveness of the intervention and whether this is in accordance with the EU Directive 2010/63. 136 adult male WistarHan rats were assigned to three groups: Sham-laparotomy (Sham) [7 days post-surgical survival time]; 50% partial hepatectomy (PH); 70% PH [PH groups with 1, 3, or 7 days post-surgical survival times]. Post-surgical severity assessment was performed via several multimodal assessment tools: I) model-specific score sheet focusing on body weight, general condition, spontaneous behavior, and the animals’ willingness to move as well as on wound healing; II) Open Field tests evaluating the total distance and velocity an animal moved within 10 minutes and its rearing behavior during the test; III) telemetric data analyzing heart rate and blood pressure; and IV) analysis of blood (AST, ALT, and hemogram) and fecal samples (fecal corticosterone metabolites). Significant differences among the experimental groups and models were observed. We demonstrated that the Open Field test can detect significant changes in severity levels. Sham-laparotomy and removal of 50% of the liver mass were associated with comparable severity (mild–moderate); the severity parameters returned to baseline levels within seven days. Removal of 70% of the liver tissue seemed to be associated with a moderate severity grade and entailed a longer recovery period (>7 days) for complete regeneration. We recommend the use of Open Field tests as part of multimodal objective severity assessment.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Assessing the severity of laparotomy and partial hepatectomy in male rats—A multimodal approach

et al. 2021

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“…The consequences of AILI on expression and activities of CYPs during the recovery stages from injury were investigated in the current study. Impact on CYPs during liver regeneration was previously studied in the partial hepatectomy (PH) mouse model (Fujino et al, 2019). However, AILI has major differences in injury and recovery patterns compared to PH (Clemens et al, 2019), therefore potentially giving rise to different consequences on recovery of CYP expression and function.…”

Section: Discussionmentioning

confidence: 99%

Alterations of Cytochrome P450–Mediated Drug Metabolism during Liver Repair and Regeneration after Acetaminophen-Induced Liver Injury in Mice

et al. 2021

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Acetaminophen (APAP)-induced liver injury (AILI) is the leading cause of acute liver failure in the United States, but its impact on metabolism, therapeutic efficacy, and adverse drug reactions (ADRs) of co-and/or subsequent administered drugs are not fully investigated. The current work explored this field with a focus on the AILI-mediated alterations of cytochrome P450 (CYP)-mediated drug metabolism. Various levels of liver injury were induced in mice by treatment with APAP at 0, 200, 400, and 600 mg/kg. Severity of liver damage was determined at 24, 48, 72, and 96 hours by plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), microRNA miR122, and tissue staining. The expression and activities of CYP3A11, 1A2, 2B10, 2C29, and 2E1 were measured. Sedation efficacy and ADRs of midazolam, a CYP3A substrate, were monitored after APAP treatment. ALT, AST, and miR122 increased at 24 hours after APAP treatment with all APAP doses, while only 200 and 400 mg/kg treated groups recovered back to normal levels at 72 and 96 hours. The expression and activity of the CYPs significantly decreased at 24 hours with all APAP doses, but only recovered back to normal at 72 and 96 hours with 200 and 400, but not 600 mg/kg of APAP. The alterations of CYP activities resulted in altered sedation efficacy and ADRs of midazolam, which were corrected by dose justification of midazolam. Overall, this work illustrated a low-CYP expression window after AILI, which can decrease drug metabolism and negatively impact drug efficacy and ADRs.

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Temporal Dynamics of Metabolic Acquisition in Grafted Engineered Human Liver Tissue

et al. 2022

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Liver disease affects millions globally, and end‐stage liver failure is only cured by organ transplant. Unfortunately, there is a growing shortage of donor organs as well as inequitable access to transplants across populations. Engineered liver tissue grafts that supplement or replace native organ function can address this challenge. While engineered liver tissues have been successfully engrafted previously, the extent to which these tissues express human liver metabolic genes and proteins remains unknown. Here, it is built engineered human liver tissues and characterized their engraftment, expansion, and metabolic phenotype at sequential stages post‐implantation by RNA sequencing, histology, and host serology. Expression of metabolic genes is observed at weeks 1–2, followed by the cellular organization into hepatic cords by weeks 4–9.5. Furthermore, grafted engineered tissues exhibited progressive spatially restricted expression of critical functional proteins known to be zonated in the native human liver. This is the first report of engineered human liver tissue zonation after implantation in vivo, which can have important translational implications for this field.

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Coordinated cytochrome P450 expression in mouse liver and intestine under different dietary conditions during liver regeneration after partial hepatectomy

Cited by 7 publications

References 53 publications

Assessing the severity of laparotomy and partial hepatectomy in male rats—A multimodal approach

Assessing the severity of laparotomy and partial hepatectomy in male rats—A multimodal approach

Alterations of Cytochrome P450–Mediated Drug Metabolism during Liver Repair and Regeneration after Acetaminophen-Induced Liver Injury in Mice

Temporal Dynamics of Metabolic Acquisition in Grafted Engineered Human Liver Tissue

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