Time-related alterations of superoxide radical levels in diverse organs of bile duct-ligated rats

Grintzalis, Konstantinos; Papapostolou, Ioannis; Assimakopoulos, Stelios F.; Mavrakis, Adamantios; Faropoulos, Konstantinos; Karageorgos, Nikolaos; Georgiou, Christos D.; Chroni, Elisabeth; Konstantinou, Dimitrios

doi:10.1080/10715760903062903

Cited by 19 publications

(13 citation statements)

References 30 publications

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“…A reduction in bile acid release may also reduce the absorption of fatty acids (and lipids and fat soluble vitamins) from the intestine and cause the observed lack in metabolic response. Moreover, this person had a high pro-oxidative-stress response which is known to be related to biliary obstruction [14,15]. Also, the position of subject 19 in the health space was distinctly different than the others.…”

Section: Discussionmentioning

confidence: 99%

Visualization and identification of health space, based on personalized molecular phenotype and treatment response to relevant underlying biological processes

Bouwman¹,

Vogels

Wopereis³

et al. 2012

BMC Med Genomics

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BackgroundBeing able to visualize multivariate biological treatment effects can be insightful. However the axes in visualizations are often solely defined by variation and thus have no biological meaning. This makes the effects of treatment difficult to interpret.MethodsA statistical visualization method is presented, which analyses and visualizes the effects of treatment in individual subjects. The visualization is based on predefined biological processes as determined by systems-biological datasets (metabolomics proteomics and transcriptomics). This allows one to evaluate biological effects depending on shifts of either groups or subjects in the space predefined by the axes, which illustrate specific biological processes. We built validated multivariate models for each axis to represent several biological processes. In this space each subject has his or her own score on each axis/process, indicating to which extent the treatment affects the related process.ResultsThe health space model was applied to visualize the effects of a nutritional intervention, with the goal of applying diet to improve health. The model was therefore named the 'health space' model. The 36 study subjects received a 5-week dietary intervention containing several anti-inflammatory ingredients. Plasma concentrations of 79 proteins and 145 metabolites were quantified prior to and after treatment. The principal processes modulated by the intervention were oxidative stress, inflammation, and metabolism. These processes formed the axes of the 'health space'. The approach distinguished the treated and untreated groups, as well as two different response subgroups. One subgroup reacted mainly by modulating its metabolic stress profile, while a second subgroup showed a specific inflammatory and oxidative response to treatment.ConclusionsThe 'health space' model allows visualization of multiple results and to interpret them. The model presents treatment group effects, subgroups and individual responses.

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Section: Discussionmentioning

confidence: 99%

Visualization and identification of health space, based on personalized molecular phenotype and treatment response to relevant underlying biological processes

Bouwman¹,

Vogels

Wopereis³

et al. 2012

BMC Med Genomics

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“…ADMA was reported to induce NADPH oxidase‐dependent superoxide production (Veresh et al, 2008). Superoxide production has been found increased in variety organs in BDL‐treated adult rats (Assimakopoulos et al, 2008; Grintzalis et al, 2009). The p22 phox is a major subunit of NADPH oxidase and was investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine

Huang

Chen

Sheen

et al. 2009

Intl J of Devlp Neuroscience

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Bile duct ligation (BDL) in developing rats causes cholestasis, impaired liver function and cognition. Because both nitric oxide (NO) and ammonia are implicated in hepatic encephalopathy (HE), we hypothesized that asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and ammonia affect cognition in young rats with BDL. Four groups of young male Sprague-Dawley rats ages 17 days were used: rat underwent laparotomy (SC group), rat underwent laparotomy plus a 30% ammonium acetate diet (SC+HA group), rat underwent BDL (BDL group), rats underwent BDL plus high ammonia diet (BDL+HA group). Spatial memory was assessed by Morris water maze task. Plasma was collected for biochemical and ADMA analyses. Liver and brain cortex were collected for determination of protein arginine methyltransferase-1 (PRMT1, ADMA-synthesizing enzyme) and dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme). We found BDL group had significantly higher plasma direct/total bilirubin, aspartate aminotransferase, alanine aminotransferase, ADMA, liver p22(phox), and worse spatial performance as compared with SC group. High ammonia diet increased plasma ammonia and ADMA concentration, and aggravated spatial deficit in the presence of BDL-induced cholestasis. We conclude plasma ADMA plays a role in BDL-induced spatial deficit. High ammonia aggravated the spatial deficits encountered in cholestatic young rats.

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“…Hyogo et al, examined the expression of hepatic adenosine triphosphatebinding cassette (ABC) transport proteins and their mRNA levels in canalicular membrane vesicles isolated from rat liver after BDL and observed a clear increase in the mRNA expression levels of multiple drug resistance-Pgp (MDR-Pgp) and MDR1b [35]. In addition, oxidative stress was observed in the blood, liver, intestine, kidney, and brain of BDL rats [36,37]. The findings of our previous studies indicate that oxidative stress-induced impairments may affect the affinity of lipophilic drugs (binding or penetrating) for erythrocyte membranes and thus increase the drug distribution to erythrocytes in a rat model of ferric-nitrilotriacetate-induced oxidative stress [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus in rats

Kobuchi¹,

Fukushima²,

Maeda³

et al. 2013

Interact Med Chem

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Background: To investigate the effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus, the pharmacokinetics of tacrolimus in rats with bile duct ligation were evaluated and the effects of the amount of intestinal bile on intestinal tacrolimus absorption were determined. Methods:In vivo pharmacokinetic studies and in vitro metabolic studies in rats with bile duct ligation were performed. In addition, an in situ absorption study was performed. Results: After an intravenous bolus injection of tacrolimus, the area under the blood concentration-time curve in rats with bile duct ligation was approximately 1.9-fold greater than that in control rats. The total clearance and steady-state volume of distribution decreased in the rats with bile duct ligation by 44.1% and 40.4%, respectively. Moreover, the production ratios of demethyl-tacrolimus and hydroxy-tacrolimus in the hepatic microsomes of rats with bile duct ligation were 59-62% and 21-43%, respectively, lower than the corresponding ratios in control rats. The area under the blood concentration-time curve after intraloop administration of tacrolimus with double-diluted bile or with saline was significantly lesser than that with undiluted bile. Significant positive linear correlations were observed between the amount of intestinal bile and the area under the blood concentration-time curve of tacrolimus (r=0.999, p<0.05). Conclusions:The decrease in the hepatic intrinsic clearance of tacrolimus in rats with bile duct ligation suggests that the bile duct stricture might contribute to the clinically observed inter-and intra-patient pharmacokinetic variability. The amount of bile in the intestine is an important factor that should be considered during tacrolimus treatment. When the route of administration of tacrolimus is changed from injection to an oral one or during long-term oral administration of tacrolimus in patients with bile duct stricture, the decrease in absorption should be taken into account, and the dose should be adjusted accordingly. Taken together, the data indicate that personalized therapy is required for patients with bile duct stricture, and it is necessary to carefully evaluate therapeutic drug monitoring data for tacrolimus.

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Time-related alterations of superoxide radical levels in diverse organs of bile duct-ligated rats

Cited by 19 publications

References 30 publications

Visualization and identification of health space, based on personalized molecular phenotype and treatment response to relevant underlying biological processes

Visualization and identification of health space, based on personalized molecular phenotype and treatment response to relevant underlying biological processes

The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine

Effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus in rats

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