Measurement of Phosphatidylcholine Hydroperoxide in Mild Ischemia-Reperfusion Injury in Rat Intestine.

Masuko, Tsuyoshi; Funayama, Yuji; Naitö, Hiroo; Fukushima, Kunihiro; Shibata, Chikashi; Takahashi, Ken; Ogawa, Hitoshi; Ueno, Tatsuya; Hashimoto, Akihiko; Miyazawa, Teruo; Nakagawa, Kiyotaka; Matsuno, Seiki; Sasaki, Iwao

doi:10.1620/tjem.198.223

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…Nevertheless, the study had some limitations, particularly with respect to the animal modeling of intestinal ischemia in humans. Our mouse model took no account of reperfusion injury that is commonplace in many other experimental models [33,34]. The gut microbiota has been implicated in the systemic inflammatory response to intestinal ischemia [10], but we made no determinations on the gut microbiota during our experiments.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic markers for intestinal ischemia in a mouse model

Fahrner

Beyoğlu

Beldi

et al. 2012

Journal of Surgical Research

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Background Diagnosis of intestinal ischemia remains a clinical challenge. The aim of the present study was to use a metabolomic protocol to identify upregulated and downregulated small molecules (Mr < 500) in the serum of mice with intestinal ischemia. Such molecules could have clinical utility when evaluated as biomarkers in human studies. Methods A mouse model for intestinal ischemia was established and validated using histology and serum tumor necrosis factor α concentrations. A second mouse model of peritoneal sepsis was used as a positive control. Serial serum samples were collected from these and from sham-operated animals. Sera were analyzed by gas chromatography–mass spectrometry for 40 small molecules as their trimethylsilyl and O-methyloxime derivatives. Peak areas were normalized against an internal standard and resultant peak area ratios subjected to multivariate data analysis using unsupervised principal components analysis and supervised orthogonal projection to latent structures–discriminant analysis. Upregulated and downregulated serum molecules were identified from their correlation to the orthogonal projection to latent structures–discriminant analysis model. Results Three highly significantly upregulated (fold-change) serum molecules in intestinal ischemia were inorganic phosphate (2.4), urea (4.3), and threonic acid (2.9). Five highly significantly downregulated (fold-change) serum molecules were stearic acid (1.7), arabinose (2.7), xylose (1.6), glucose (1.4), and ribose (2.2). Lactic acid remained unchanged in intestinal ischemia. Conclusions Distinct molecular changes are reported here for the first time in intestinal ischemia. They reveal impairments of gut microbiota metabolism, intestinal absorption, and renal function, together with increased oxidative stress. In contrast to other reports, lactic acid was not significantly changed. These molecular signatures may now be evaluated in clinical studies.

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Section: Discussionmentioning

confidence: 99%

Metabolomic markers for intestinal ischemia in a mouse model

Fahrner

Beyoğlu

Beldi

et al. 2012

Journal of Surgical Research

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“…In recent years, it has been emphasized that free oxygen radicals, derived ischemia-reperfusion injuries in different tissues, are important in the formation of tissue damage (Masuko et al 2002;Aikawa et al 2003;Jeyabalan et al 2006;Guz et al 2007). Ischemia-reperfusion mechanisms may cause an oxidative stress injury in a fractured extremity.…”

Section: Discussionmentioning

confidence: 99%

Time-Dependent Changes in Serum Nitric Oxide Levels after Long Bone Fracture

Keskin

Kızıltunç

2007

Tohoku J. Exp. Med.

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Nitric oxide (NO) is a free radical of physiological signifi cance. The changes in the production of NO during the fracture healing process are not well known. This clinical prospective study was planned to determine these changes in patients with fractured long bone(s), who underwent surgery in the 3rd week after fracture. The patients were divided into two groups: 20 patients with an isolated femoral fracture and 20 patients with multiple fractures, including a femoral fracture. Venous blood was drawn from the healthy volunteers (n = 20) once, and from the patients seven times during 21 days after fracture. NO level was measured as nitrite in each serum sample. The serum NO levels at all measurements of the patients were signifi cantly higher than those of the control subjects. The timedependent changes in the NO levels were similar in both patient groups. The serum NO levels were highest in the fi rst 6 hrs, and then decreased to the lowest level on the 3rd day. Subsequently, there was an increasing trend on the 5th, 7th and 14th days. At all times of the measurements, the NO levels were higher in patients with multiple fractures than in those with the femoral fracture, with the signifi cant difference observed at the 6 hrs and on the 7th day. The NO levels were decreased on the 21st day after surgery. The present study suggests that NO production may be increased in considerable amounts during the fi rst 2 weeks of fracture healing, particularly in the fi rst 6 hrs.human; bone; fracture; blood; nitric oxide © 2007 Tohoku University Medical PressNitric oxide (NO) is a physiological free radical, synthesized from the amino acid L-arginine by the 3 NO synthase (NOS) isoforms; neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). It functions in vascular regulation, host immune defense, neurotransmission, and other systems. While some diseases, like vascular dysfunctions, impair NO production, some diseases, like septic schock, cerebral infarction, diabetes mellitus and neurodegenerative disorders, augment NO production (Mori and Gotoh 2004). It is not clear how NO affects bone cells. Some studies show that NO has a biphasic effect on bone cell activity. It has been stated that moderate concentrations of NO produced by eNOS in the bone is necessary for normal osteoblast growth and fracture healing (Ralston 1997;Corbett et al. 1999). However, it was suggested that high concentrations of NO produced by cytokine-induced iNOS activity may inhibit the

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“…Several studies have shown that P-gp expression level is altered by intestinal I/R, but results regarding alteration of P-gp expression are not consistent among those studies (7)(8)(9). Some procedural differences exist among these intestinal I/R model rats, such as ischemia duration, grade of ischemia and reperfusion time, which have been shown to affect the extent of intestinal I/R injury (9,12,22). Thus, there were differences in the amount of generated ROS after intestinal I/R among those studies, resulting in the difference in the alteration of P-gp expression.…”

Section: Discussionmentioning

confidence: 99%

Intestinal P-glycoprotein Expression is Multimodally Regulated by Intestinal Ischemia-Reperfusion

et al. 2014

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Purpose. Reactive oxygen species (ROS) have multiple physiological effects that are amount-dependent. ROS are one of the causes of intestinal ischemia-reperfusion (I/R) injury. In this study, we investigated whether the amount of ROS and the degree of intestinal I/R injury affect the expression level of P-glycoprotein (P-gp). Methods. We used hydrogen peroxide (H2O2) as ROS in in vitro experiments. Intestinal I/R model rats, which were subjected 15-min ischemia (I/R-15), were used in in vivo experiments. Results. P-gp expression in Caco-2 cells was increased in response to 1 µM of H2O2 but decreased upon exposure to 10 mM of H2O2. We previously reported that P-gp expression is decreased after intestinal I/R with 30-min ischemia (I/R-30), which time a large amount of ROS is generated. I/R-15 induced slightly less mucosal and oxidative injury than did I/R-30. P-gp expression in the jejunum was increased at 1 h after I/R-15, and ileal paracellular permeability was increased. The blood concentration of tacrolimus, a P-gp substrate, was lower during 0-20 min but was higher during 40-90 min post-administration compared with that in the sham-operated rats. P-gp expression in the ileum was decreased at 6 h after I/R-15, due to abnormal localization of P-gp, resulting in a high blood tacrolimus concentration in rats reperfused for 6 h. Conclusions. ROS multimodally regulate P-gp expression depending on its amount. This is important for understanding the pattern of P-gp expression after intestinal I/R. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Measurement of Phosphatidylcholine Hydroperoxide in Mild Ischemia-Reperfusion Injury in Rat Intestine.

Cited by 5 publications

References 17 publications

Metabolomic markers for intestinal ischemia in a mouse model

Metabolomic markers for intestinal ischemia in a mouse model

Time-Dependent Changes in Serum Nitric Oxide Levels after Long Bone Fracture

Intestinal P-glycoprotein Expression is Multimodally Regulated by Intestinal Ischemia-Reperfusion

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