Glucose Induces ER Stress Response-Mediated Peritoneal Mesothelial Cell Death.

Peritoneal dialysis (PD) fluid, which contains a high concentration of glucose, is involved in peritoneal damage after long-term use. The mechanisms through which glucose induces damage to the mesothelium have not been clearly elucidated. Although, endoplasmic reticulum (ER) stress response is associated with several diseases, the involvement of ER stress in peritoneal damage has not yet been demonstrated. Primary-cultured rat peritoneal mesothelial cells (RPMCs) and rat PD model were used to investigate the influence of glucose on the peritoneum. Cells treated with glucose were examined for cytotoxicity, induction of apoptosis, and activation of the ER stress pathway. Glucose treatment of RPMCs induced cell death at concentrations higher than 3%. Annexin V positive, that is a feature of apoptosis, occurred in dead cells. Treatment with glucose led to the activation of protein kinase R-like ER kinase (PERK) and eukaryotic translation initiation factor-2α (eIF-2α). Glucose also induced the expression and nuclear translocation of homologous protein C/EBP. Cell death was rescued by the integrated stress response inhibitor, ISRIB, which suppresses the integrated stress response pathway, including ER stress. Glucose in PD fluid induces PERK/eIF-2α-mediated ER stress in RPMCs, resulting in apoptosis. This cellular stress may cause peritoneal damage in patients receiving PD.

Caspase-4 has a role in cell division in epithelial cells through actin depolymerization.

In addition to its role in pyroptosis and inflammatory cytokine maturation, caspase-4 (CASP4) also contributes to the fusion of phagosomes with lysosomes and cell migration. However, its role in cell division remains elusive. In this study, we demonstrate that CASP4 is indispensable for proper cell division in epithelial cells. Knockout of CASP4 (CASP4 KO) in HepG2 cells led to delayed cell proliferation, increased cell size, and increased multinucleation. In mitosis, CASP4 KO cells showed multipolar spindles, asymmetric spindle positioning, and chromosome segregation errors, ultimately increasing DNA content and chromosome number. We also found that phalloidin, a marker of filamentous actin, increased in CASP4 KO cells owing to suppressed actin depolymerization. Moreover, the levels of actin polymerization-related proteins, including Rho-associated protein kinase1 (ROCK1), LIM kinase1 (LIMK1), and phosphorylated cofilin, significantly increased in CASP4 KO cells. These results suggest that CASP4 contributes to proper cell division through actin depolymerization.

The expression of matrix metalloproteinase-12 in the peritoneum of rats with continuous peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an important alternative treatment for end-stage renal disease. Continuous exposure to non-physiological fluids during PD is associated with pathological responses, such as sustained microinflammation, leading to tissue fibrosis and angiogenesis. However, the effect of PD fluid on submesothelial cells has not yet been investigated in detail. METHODS: We investigated the association between macrophages and the expression of matrix metalloproteinase-12 (MMP-12), an elastin proteinase secreted by macrophages, in the peritoneal tissue of rats undergoing continuous PD. RESULTS: Morphological data revealed that the submesothelial layer of the peritoneum in PD model rats was markedly thickened, with fibrosis and angiogenesis. In the fibrillization area, elastin was disorganized and fragmented, and macrophages accumulated, which tended to have M2 characteristics. The expression of MMP-12 was enhanced by continuous exposure to PD fluid, suggesting that MMP-12 expression may be involved in PD fluid-induced peritoneal damage. CONCLUSIONS: The results of this study may lead to a better understanding of the mechanisms underlying fibrosis in PD.

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats.

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

Pentacyclic triterpenoid ursolic acid induces apoptosis with mitochondrial dysfunction in adult T-cell leukemia MT-4 cells to promote surrounding cell growth.

We investigated the antitumor effects of oleanolic acid (OA) and ursolic acid (UA) on adult T-cell leukemia cells. OA and UA dose-dependently inhibited the proliferation of adult T-cell leukemia cells. UA-treated cells showed caspase 3/7 and caspase 9 activation. PARP cleavage was detected in UA-treated MT-4 cells. Activation of mTOR and PDK-1 was inhibited by UA. Autophagosomes were detected in MT-4 cells after UA treatment using electron microscopy. Consistently, mitophagy was observed in OA- and UA-treated MT-4 cells by confocal microscopy. The mitochondrial membrane potential in MT-4 cells considerably decreased, and mitochondrial respiration and aerobic glycolysis were significantly reduced following UA treatment. Furthermore, MT-1 and MT-4 cells were sorted into two regions based on their mitochondrial membrane potential. UA-treated MT-4 cells from both regions showed high activation of caspase 3/7, which were inhibited by Z-vad. Interestingly, MT-4 cells cocultured with sorted UA-treated cells showed enhanced proliferation. Finally, UA induced cell death and ex vivo PARP cleavage in peripheral blood mononuclear cells from patients with adult T-cell leukemia. Therefore, UA-treated MT-4 cells show caspase activation following mitochondrial dysfunction and may produce survival signals to the surrounding cells.

Paneth cell maturation is related to epigenetic modification during neonatal-weaning transition.

Paneth cells are antimicrobial peptide-secreting epithelial cells located at the bottom of the intestinal crypts of Lieberkühn. The crypts begin to form around postnatal day 7 (P7) mice, and Paneth cells usually appear within the first 2 weeks. Paneth cell dysfunction has been reported to correlate with Crohn's disease-like inflammation, showing narrow crypts or loss of crypt architecture in mice. The morphology of dysfunctional Paneth cells is similar to that of Paneth/goblet intermediate cells. However, it remains unclear whether the formation of the crypt is related to the maturation of Paneth cells. In this study, we investigated the histological changes including epigenetic modification in the mouse ileum postnatally and assessed the effect of the methyltransferase inhibitor on epithelium development using an organoid culture. The morphological and functional maturation of Paneth cells occurred in the first 2 weeks and was accompanied by histone H3 lysine 27 (H3K27) trimethylation, although significant differences in DNA methylation or other histone H3 trimethylation were not observed. Inhibition of H3K27 trimethylation in mouse ileal organoids suppressed crypt formation and Paneth cell maturation, until around P10. Overall, our findings show that post-transcriptional modification of histones, particularly H3K27 trimethylation, leads to the structural and functional maturation of Paneth cells during postnatal development.

Expression of T-Type Voltage-Gated Calcium Channel in the Cilia of Human Nasal Epithelial Cells.

INTRODUCTION: The mucociliary transport function of the airway epithelium is largely dependent on ciliary beating. The control signal of ciliary beating is thought to be intracellular Ca2+. We herein investigated the expression of T-type voltage-gated calcium channel (VGCC), a generator of intracellular Ca2+ oscillation, in the human nasal mucosa. METHODS: The inferior turbinate was collected from patients with chronic hypertrophic rhinitis. The expression of T-type VGCC α1 subunits was examined by immunohistochemistry, transmission immunoelectron microscopy, Western blot, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Participation of T-type VGCC in the ciliary beat regulation was examined by pharmacological inhibition tests using specific blockers of T-type VGCC in ex vivo measurements of the ciliary beat frequency (CBF) and ATP release and in intracellular Ca2+ imaging of isolated ciliated cells. RESULTS: Immunohistochemical staining showed the expressions of T-type VGCC α1 subunits, Cav3.1 and Cav3.3, on the surface of the epithelial cells. At the ultrastructural level, immunoreactivity for Cav3.1 was localized on the surface of the cilia, and that for Cav3.3 was localized in the cilia and at the base of the cilia. The existence of Cav3.1 and Cav3.3 was confirmed at the protein level by Western blot and at the transcriptional level by real-time RT-PCR. Specific blockers of T-type VGCC, mibefradil and NNC 55-0396, significantly inhibited CBF. These blockers also inhibited a CBF increase induced by 8-bromo-cAMP/8-bromo-cGMP and significantly lowered the intracellular Ca2+ level of isolated ciliated cells in a time-dependent manner. On the other hand, the ATP release from the nasal mucosa was not changed by mibefradil or NNC 55-0396. CONCLUSION: These results indicate that T-type VGCC α1 subunits, Cav3.1 and Cav3.3, exist at the cilia of the nasal epithelial cells and participate in the regulation of ciliary beating and that these channels act downstream of cAMP/cGMP.

Trehalose alleviates oxidative stress-mediated liver injury and Mallor-Denk body formation via activating autophagy in mice.

Autophagy is a degradation pathway for long-lived cytoplasmic proteins or damaged organelles and also for many aggregate-prone and disease-causing proteins. Endoplasmic reticulum (ER) stress and oxidative stress are associated with the pathophysiology of various liver diseases. These stresses induce the accumulation of abnormal proteins, Mallory-Denk body (MDB) formation and apoptosis in hepatocytes. A disaccharide trehalose had been reported to induce autophagy and decrease aggregate-prone proteins and cytotoxicity in neurodegenerative disease models. But the effects of trehalose in hepatocytes have not been fully understood. We examined the effect of trehalose on autophagy, ER stress and oxidative stress-mediated cytotoxicity and MDB formation in hepatocytes using mice model with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment for 3 months. We administered trehalose by intraperitoneal injection of water containing 10% trehalose (0.02 mg/g body weight) every other day for 3 months. Our results demonstrated that trehalose induced autophagy and reduced ER stress, oxidative stress, MDB formation and apoptosis in hepatocytes of DDC-fed mice by Western blotting and immunostaining analyses. Electron microscopy revealed that trehalose induced autolysosome formation, which located is close to the MDBs. Thus, our findings suggest that trehalose can become a therapeutic agent for oxidative stress-related liver diseases via activating autophagy.

Particulate Matter, Asian Sand Dust Delays Cyclophosphamide-induced Type 1 Diabetes in NOD Mice.

Although it is known that desert dust exacerbates allergic diseases, how it affects the onset of autoimmune diseases is unclear. No epidemiological investigations or animal experiments have been conducted so far to elucidate the effects of desert dust on autoimmune diseases. Here, we focused on particulate matter, such Asian sand dust (ASD) that has been known to cause adverse health effects in East Asian countries, and conducted animal experiments to examine how ASD influences type 1 diabetes (T1D), an autoimmune disease. An ASD suspension was intratracheally administered into NOD mice, which spontaneously develop T1D, for 4 times at 2-week intervals. Subsequently, the incidence of cyclophosphamide (CY)-induced diabetes was examined, which was then quantified using adoptive splenocyte-transfer assays. Kaplan-Meier curves of the cumulative T1D incidence were compared using the log-rank test, and unpaired two-tailed t tests were used for comparing the other data. We observed that ASD administration delayed T1D, and adoptive splenocytes derived from ASD-administered donor NOD mice also delayed the onset of T1D in recipient NOD mice. We further found that ASD increases concanavalin A-induced IFN-γ production and decreases regulatory T cells. Consequently, ASD suppresses the onset of T1D, activates spleen cells, and affects T-cell differentiation.

Calmodulin and protein kinases A/G mediate ciliary beat response in the human nasal epithelium.

BACKGROUND: Mucociliary clearance of the airway epithelium is an essential function for mucosal defense. We recently proposed a hypothetical mechanism of ciliary beat regulation, in which the pannexin-1 (Panx1)-P2X7 unit serves as an oscillator generating a periodic increase in intracellular Ca2+ ([Ca2+ ]i ). In the present study, we examined the localization of Panx1 and P2X7 at the ultrastructural level, and investigated the regulatory pathway subsequent to [Ca2+ ]i increase. METHODS: The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic sinonasal surgery. The mucosa was examined by transmission immunoelectron microscopy for Panx1 and P2X7. Alternatively, the mucosa was cut into thin strips, and ciliary beat frequency (CBF) was measured under a phase-contrast light microscope with a high-speed digital video camera. RESULTS: In immunoelectron microscopy, immunoreactivities for Panx1 and P2X7 were localized along the plasma membrane of the entire length of the cilia. CBF was significantly increased by stimulation with 100 µM acetylcholine (Ach). The Ach-induced CBF increase was significantly inhibited by calmidazolium (calmodulin antagonist), SQ22536 (adenylate cyclase inhibitor), ODQ (guanylate cyclase inhibitor), KT5720 (protein kinase A inhibitor), and KT5823 (protein kinase G inhibitor). Fluorodinitrobenzene (creatine kinase inhibitor) completely inhibited the ciliary beat in a time- and dose-dependent manner. CONCLUSION: These results indicate that Panx1 and P2X7 coexist at the cilia of the human nasal epithelial cells and that the ciliary beat is regulated by calmodulin, adenylate/guanylate cyclases and protein kinases A/G, and crucially depends on creatine kinase.

Trehalose activates autophagy and decreases proteasome inhibitor-induced endoplasmic reticulum stress and oxidative stress-mediated cytotoxicity in hepatocytes.

AIM: Endoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative stress, cytoplasmic inclusion body formation, and apoptosis in hepatocytes. Autophagy is a bulk degradation pathway for long-lived cytoplasmic proteins or damaged organelles and is also a major degradation pathway for many aggregate-prone and disease-causing proteins. We previously reported that rapamycin, a mammalian target of rapamycin inhibitor, activated autophagy and decreased proteasome inhibitor-mediated ubiquitinated protein accumulation, cytoplasmic inclusion body formation, and apoptosis in hepatocytes. Trehalose is a non-reducing disaccharide that has been shown to activate autophagy. It has been reported to decrease aggregate-prone proteins and ameliorate cytotoxicity in neurodegenerative disease models. However, the effects of trehalose in hepatocytes are unclear. METHODS: We show here that trehalose activated autophagy and reduced endoplasmic reticulum stress, cytoplasmic inclusion body formation, and apoptosis in proteasome inhibitor-treated liver-derived cultured cells. CONCLUSION: To our knowledge, this is the first report showing that trehalose activates autophagy and has cytoprotective effects in hepatocytes. Our findings suggest that trehalose can become a therapeutic agent for endoplasmic reticulum stress-related liver diseases.

Accuracy of follicle count and ovulation confirmation using magnetic resonance imaging in microminipigs with normal estrus cycles.

Magnetic resonance imaging (MRI) is suggested to be useful for counting follicles and confirming ovulation in microminipigs. However, its accuracy is unknown. We have compared the number of follicles counted by MRI to that of corpus hemorrhagicum confirmed directly by visual inspection. The follicles of 17 microminipigs were counted by using ovarian MRI on a 0.4 Tesla MRI System every 24 hr after estrus until follicle images disappeared. Then, we performed laparotomy to count their corpus hemorrhagicum. Significant correlation was observed between follicle counts obtained using MRI (5.18 ± 1.78 per head) and the numbers of corpus hemorrhagicum (5.47 ± 1.74 per head). In conclusion, follicle counts using 0.4-T MRI were reliable, and confirmed microminipig ovulation.

Characterization of the Potent Odorants Contributing to the Characteristic Aroma of Matcha by Gas Chromatography-Olfactometry Techniques.

The odorants contributing to the characteristic aroma of matcha were investigated by analysis of the headspace samples and the volatile fractions prepared by a combination of solvent extraction and the SAFE techniques using three matcha powders of different grades (high, medium, and low). Gas chromatography-olfactometry of the headspace samples (GCO-H) and aroma extract dilution analysis (AEDA) applied to the volatile fractions revealed 16 (FD factor ≥1) and 39 (FD factor ≥43) odor-active peaks, respectively. Among them, 14 and 37 of the odorants, most of which were newly detected in matcha, were identified or tentatively identified by GC-MS and GC-O, respectively. By comparing the perceived odorants of three matcha powders, it was revealed that eight compounds with sweet, green, metallic, and floral notes showed high flavor dilution (FD) factors irrespective of the grades. In addition, some odorants were suggested to influence the characteristic aroma of each grade. Furthermore, trans-4,5-epoxy-(E)-2-decenal, one of the potent odorants of matcha, was revealed to exist as a racemic mixture in matcha. This result suggested that trans-4,5-epoxy-(E)-2-decenal is formed by a nonenzymatic reaction in matcha, different from that in black tea, and that the unique manufacturing process of matcha has a close connection with its formation.

Corrigendum to "High glucose concentration-induced expression of pentraxin-3 in a rat model of continuous peritoneal dialysis".

This correct the article DOI: 10.14670/HH-11-756.

Lipid-Induced Endoplasmic Reticulum Stress Impairs Selective Autophagy at the Step of Autophagosome-Lysosome Fusion in Hepatocytes.

Blockage of hepatic autophagic degradation system occurs in obesity and is associated with the development of nonalcoholic fatty liver disease. However, the mechanism of this blockage remains unclear. We found a high-fat diet induced accumulation of autophagosomes in the mice livers. However, autophagy substrates such as p62 and ubiquitinated proteins also accumulated in the livers in this model. These findings indicate the possibility that a high-fat diet impairs autophagic flux in the liver. Then, to assess the autophagic flux in more detail, we performed analyses of autophagic flux in cultured hepatocytes exposed to monounsaturated fatty acids (FAs) or saturated FAs (SFAs). SFAs but not monounsaturated FAs suppressed degradation of contents in the autophagosomes. We analyzed each stage of the autophagy pathway (ie, autophagosome formation, autophagosome-lysosome fusion, lysosomal degradation) in cultured hepatocytes treated with monounsaturated FAs or SFAs and found that SFAs impaired autophagosome-lysosome fusion. This impairment occurred in an endoplasmic reticulum stress-dependent manner. Moreover, ubiquitin and p62-positive inclusions observed in high-fat diet-fed mice livers and SFA-treated cells were sequestered within autophagosomes. We also found that SFA-induced accumulation of Ser351-phosphorylated p62, which is indispensable for selective autophagy, further increased on administration of a lysosomal proteinase inhibitor. Although lipid-induced endoplasmic reticulum stress interferes with the autophagosome-lysosome fusion, selective autophagic sequestration of aggregated proteins is not inhibited.

High glucose concentration-induced expression of pentraxin-3 in a rat model of continuous peritoneal dialysis.

BACKGROUND: Continuous exposure to peritoneal dialysis fluids (PDFs) is associated with pathological responses such as persistent micro-inflammation, which leads to ultrafiltration failure. Pentraxin-3 (PTX3), a multifunctional soluble pattern recognition receptor, is produced at sites of inflammation by a wide range of cell types. This study investigates the in vivo expression of PTX3 in the peritoneal membrane of a rat continuous peritoneal dialysis (PD) model, as well as the effect of high glucose on the in vitro expression of PTX3. METHODS: The expression of PTX3 was analyzed using RT-PCR, real-time PCR, immunohistochemistry and western blotting in a PD rat model receiving saline or conventional PDF containing 3.86% glucose for 8 weeks. The effects of high glucose on the expression of PTX3 were examined in cultured rat peritoneal mesothelial cells (RPMCs), mouse macrophage-like cells, and mouse fibroblasts. RESULTS: In a rat model of PD, eight-week instillation of the conventional PDF produced increased submesothelial thickening, followed by substantially enhanced PTX3 protein levels in the submesothelial layer of peritoneal membrane. PTX3 was detected in peritoneal mesothelial cells, macrophages and fibroblasts in the thickened submesothelial area. Glucose was found to induce PTX3 protein expression in RPMCs as well as macrophage-like cells and fibroblasts. CONCLUSION: Continuous exposure to conventional PDF induces PTX3 expression in the peritoneal membrane of rats. High glucose may be involved in the mechanism of PDF-induced local micro-inflammation in the peritoneum.

Characterization of the potent odorants contributing to the characteristic aroma of Chinese green tea infusions by aroma extract dilution analysis.

The volatile fractions of three famous Chinese green tea cultivar infusions (Longjing, Maofeng, and Biluochun) were prepared by a combination of the adsorptive column method and the SAFE techniques. The aroma extract dilution analysis (AEDA) applied to the volatile fractions revealed 58 odor-active peaks with flavor dilution (FD) factors between 4(1) and 4(7). Forty-six of the odorants, which included six odorants that have not been reported in the literature in Chinese green tea (2-isopropyl-3-methoxypyrazine, 2-ethenyl-3,5-dimethylpyrazine, cis-4,5-epoxy-(E)-2-decenal, 4-ethylguaiacol, (E)-isoeugenol, and 3-phenylpropionic acid), were identified or tentatively identified by GC-MS and GC-O. Among the perceived odorants, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, 3-hydroxy-4,5-dimethyl-2(5H)-furanone, coumarin, vanillin, geraniol, (E)-isoeugenol, and 2-methoxyphenol showed high FD factors in all of the cultivars, irrespective of the cultivar or harvesting season, suggesting that these seven odorants are essential for the aroma of Chinese green tea. On the other hand, the contents of the odorants, FD factors of which were uneven between the cultivars, were suggested to influence the characteristic aroma of each cultivar. In addition, the formation mechanism of (E)-isoeugenol, one of the odorants which have not been reported in the literature with a high FD factor common to all the cultivars, was investigated, and it was suggested that the (E)-isoeugenol content of the tea products has a close correlation with the manufacturing process of the tea leaves.

Possible participation of acidic pH in bone resorption in middle ear cholesteatoma.

OBJECTIVES/HYPOTHESIS: The etiopathology of bone resorption in cholesteatoma is unclear. We studied pH in middle ear cholesteatoma tissue and the permeability of the cholesteatoma epithelium in an attempt to elucidate the mechanism of bone resorption in this disease. STUDY DESIGN: Laboratorial study. METHODS: Cholesteatoma tissue was collected from patients with primary acquired middle ear cholesteatoma. The pH of the keratin debris of cholesteatoma was measured using a pH meter. The cholesteatoma epithelium was examined under a confocal laser scanning microscope, and under a transmission electron microscope. Expression of filaggrin in the cholesteatoma tissue was explored by fluorescence immunohistochemistry and by quantitative reverse transcription-polymerase chain reaction. RESULTS: The pH of the keratin debris of cholesteatoma was acidic. The pH of the basal layer of the cholesteatoma epithelium was significantly lower than that of the antrum mucosa. Transmission electron microscope showed distinct penetration of lanthanum in the intercellular space of the basal, spinous, and granular layers of the cholesteatoma epithelium, but only a small amount of lanthanum in the granular layer in the normal skin. The expression of filaggrin mRNA was significantly lower in the cholesteatoma tissue than in the normal skin. CONCLUSIONS: These results indicate that acid leakage through the cholesteatoma epithelium probably participates in the resorption of the underlying bone structure. The increased permeability of the cholesteatoma epithelium may be explained by a decrease in filaggrin expression.

Food allergens are transferred intact across the rat blood-placental barrier in vivo.

We investigated the mechanism of transplacental macromolecular transport in rats on the nineteenth day of pregnancy using tracers, transmission electron microscopy and immunohistochemistry. The blood-placental barrier of full-term rat placentas was composed of a trilaminar layer of trophoblast cells that separates the fetal capillaries from the maternal blood spaces: a layer of cytotrophoblasts lining the maternal blood space and a bilayer of syncytiotrophoblast surrounding the fetal capillaries. Horseradish peroxidase, intravenously injected into the maternal circulation, was found in the maternal blood spaces, the interspaces between the cytotrophoblasts and the syncytiotrophoblast I, many pits and small vesicles in the syncytiotrophoblast I, vesicles of the syncytiotrophoblast II, fetal connective tissue and fetal capillaries. Intravenously injected ovalbumin was detected in the maternal blood spaces, a trilaminar layer and the fetal capillaries. Neonatal Fc receptor (FcRn), a receptor for IgG, was localized at the maternal side of the blood-placental barrier. These results show that the structure of the rat blood-placental barrier is quite similar to the human blood-placental barrier, and non-specific macromolecules and food allergens may penetrate through the blood-placental barrier of the full-term placenta from the maternal to fetal circulation mediated by FcRn.

Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats.

The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.