Ju-Young Jung

Protection of NAD(P)H:quinone oxidoreductase 1 against renal ischemia/reperfusion injury in mice.

UNLABELLED Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. NAD(P)H quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1(-/-) mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1(-/-) mice, the cellular NADPH/NADP(+) ratio was significantly higher and NOX activity was markedly higher than in those of NQO1(+/+) mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADP(+) ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP(+) modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.

Effect of silk fibroin nanofibers containing silver sulfadiazine on wound healing.

Background One of the promising applications of silk fibroin (SF) in biomedical engineering is its use as a scaffolding material for skin regeneration. The purpose of this study was to determine the wound healing effect of SF nanofibrous matrices containing silver sulfadiazine (SSD) wound dressings. Methods An SF nanofibrous matrix containing SSD was prepared by electrospinning. The cell attachment and spreading of normal human epidermal keratinocytes (NHEK) and normal human epidermal fibroblasts (NHEF) to SF nanofibers containing three different concentrations of SSD contents (0.1, 0.5, and 1.0 wt%) were determined. In addition, a rat wound model was used in this study to determine the wound healing effect of SF nanofibers containing SSD compared with that of Acticoat™, a commercially available wound dressing. Results The number of NHEK and NHEF attached to SF nanofibers containing SSD decreased when the concentration of SSD increased. The number of attached NHEF cells was lower than that of attached NHEK cells. The SF matrix with 1.0 wt% SSD produced faster wound healing than Acticoat, although 1.0 wt% SSD inhibited the attachment of epidermal cells to SF nanofibers in vitro. Conclusion The cytotoxic effects of SF nanofibers with SSD should be considered in the development of silver-release dressings for wound healing through its antimicrobial activity. It is challenging to design wound dressings that maximize antimicrobial activity and minimize cellular toxicity.

A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model.

Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor‐α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP‐activated protein kinase (AMPK) and nuclear factor E2‐related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase‐1, NAD(P)H quinone oxidoreductase 1, and γ‐glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti‐inflammatory, and antiapoptotic activity against ethanol‐induced liver injury. Copyright

Protective role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cisplatin-induced nephrotoxicity

Although cisplatin is widely used as an anti-cancer agent, its use is significantly limited because of its tendency to induce nephrotoxicity through poorly understood mechanisms. NAD(P)H:quinone oxidoreductase 1 (NQO1) is well known to regulate ROS generation. The purpose of this study was to investigate whether NQO1 modulates cisplatin-induced renal failure associated with NADPH oxidase (NOX)-derived ROS production in an animal model. NQO1-/- mice were treated with cisplatin (18 mg/kg) and renal function, oxidative stress, and tubular apoptosis were assessed. NQO1-/- mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In accordance with these results, the cellular NADPH/NADP ratio and NOX activity were markedly increased in the kidneys of NQO1-/- mice compared to NQO1+/+ mice. In addition, activation of NQO1 by βL treatment significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis. This study demonstrates that NQO1 protects cells against renal failure induced by cisplatin, and that this effect is mediated by decreased NOX activity via cellular NADPH/NADP modulation. These results provide convincing evidence that NQO1 might be beneficial for ameliorating renal failure induced by cisplatin.

Antioxidant and antiasthmatic effects of saucerneol D in a mouse model of airway inflammation.

Chronic airway inflammation is a hallmark of asthma, which is an immune-based disease. We evaluated the ability of saucerneol D, a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Furthermore, we determined whether heme oxygenase (HO)-1 was required for the protective activity of saucerneol D. The airways of OVA-sensitized mice exposed to an OVA challenge developed eosinophilia and mucus hypersecretion and exhibited increased cytokine levels. Mice were administered saucerneol D orally at doses of 20 and 40mg/kg once daily on days 26-30. Saucerneol D administered orally significantly inhibited the number of OVA-induced inflammatory cells and the production of immunoglobulin E as well as Th2-type cytokines. Histopathology studies revealed a marked decrease in lung inflammation and goblet cell hyperplasia after saucerneol D treatment. In addition, saucerneol D induced HO-1 and led to a marked decrease in OVA-induced reactive oxygen species and malondialdehyde and an increase in superoxide dismutase and glutathione in lung tissues. These antioxidant effects were correlated with HO-1 induction. In our experiments, saucerneol D treatment reduced airway inflammation and suppressed oxidative stress in an OVA-induced asthma model.

Red ginseng ameliorates acute cisplatin-induced nephropathy.

Korean red ginseng is one of the traditional herbal medicines most widely used in China, Korea, and Japan. To determine whether Korean red ginseng extract can mitigate acute renal nephropathy, we examined its renoprotective effects in a model of cisplatin-induced acute renal failure in Sprague Dawley rats. Korean red ginseng was administered to rats by oral gavage once a day at doses of 100, 300, or 500 mg/kg for 28 days. On day 23, the animals received an intraperitoneal injection of cisplatin (5 mg/kg) to induce acute renal failure. Body weight gain, urine volume, blood urea nitrogen and creatinine concentrations, and expression of p53 were measured. Terminal deoxynucleotidyl transferase dUTP nick end-labeling was used to analyze apoptosis. Kidney tissues from the control and experimental groups were analyzed by immunohistochemistry for inflammatory cytokines and histopathological examination. To identify the mechanism responsible for the renoprotective effects of Korean red ginseng, we measured malondialdehyde concentration as an end product of lipid peroxidation and the activities of the antioxidants superoxide dismutase and glutathione. Korean red ginseng significantly decreased the levels of indicators of renal dysfunction, inflammatory cytokine expression, apoptosis, and malondialdehyde content in the kidney and also significantly attenuated the histopathological changes associated with acute renal failure. These findings suggest that Korean red ginseng has renoprotective effects against cisplatin-induced acute renal failure by reducing oxidative stress and inflammation.

Antimicrobial Silver Chloride Nanoparticles Stabilized with Chitosan Oligomer for the Healing of Burns

Recently, numerous compounds have been studied in order to develop antibacterial agents, which can prevent colonized wounds from infection, and assist the wound healing. For this purpose, novel silver chloride nanoparticles stabilized with chitosan oligomer (CHI-AgCl NPs) were synthesized to investigate the influence of antibacterial chitosan oligomer (CHI) exerted by the silver chloride nanoparticles (AgCl NPs) on burn wound healing in a rat model. The CHI-AgCl NPs had a spherical morphology with a mean diameter of 42 ± 15 nm. The burn wound healing of CHI-AgCl NPs ointment was compared with untreated group, Vaseline ointment, and chitosan ointment group. The burn wound treated with CHI-AgCl NPs ointment was completely healed by 14 treatment days, and was similar to normal skin. Particularly, the regenerated collagen density became the highest in the CHI-AgCl NPs ointment group. The CHI-AgCl NPs ointment is considered a suitable healing agent for burn wounds, due to dual antibacterial activity of the AgCl NPs and CHI.

Platycodin D attenuates bile duct ligation-induced hepatic injury and fibrosis in mice.

Platycodin D (PD) is the major triterpene saponin in the root of Platycodon grandiflorum. The aim of the present study was to evaluate the protective effects of PD on bile duct ligation (BDL)-induced cholestasis in mice. Mice were allocated to five groups: sham, BDL alone, and BDL with PD treatment at 1, 2, and 4mg/kg. PD was administered to the mice for 28 consecutive days after the BDL operation. PD treatment of BDL-operated mice decreased serum alanine aminotransferase, serum aspartate aminotransferase, and total bilirubin levels by up to 37%, 31%, and 41%, respectively, in comparison with the levels in mice that underwent BDL alone. PD treatment attenuated oxidative stress, as evidenced by an increase in anti-oxidative enzyme levels glutathione and superoxide dismutase together with a decrease in lipid peroxidation and oxidative stress indices levels of malondialdehyde and nitric oxide. Histopathological studies further confirmed the protective effects of PD on cholestasis-induced hepatic injury and liver fibrosis in mice. In addition, nuclear factor-kappa B and inducible nitric oxide synthase levels significantly decreased after PD treatment, as did the levels of hepatocyte apoptosis. Taken together, these results suggest that PD treatment might be beneficial in cholestasis-induced hepatotoxicity.

Chordoma in the tail of a ferret.

A chordoma is an uncommon tumor that originates from the remnants of the notochord and most commonly involves the cranial and caudal regions of the axial skeleton. Chordoma has been described in laboratory animals such as dogs, rats, minks, and ferrets. This report describes a case of a chordoma in the tail of a ferret. Grossly, a grayish-white, expansile, subcutaneous soft-tissue mass was observed in the tail. Histopathologically, the mass was a loosely placed, nodular, unencapsulated neoplasm within the dermis. In the mass, tumor lobules were intermingled with fibrous tissues. Fibrous tissues contained abundant extracellular basophilic material that was consistent with mucin. The tumor was composed of a close pack of adipocyte-like vacuolated cells (physaliferous cells). The cells were centrally or eccentrically located round nuclei and eosinophilic cytoplasm with large vacuoles. Immunohistologically, neoplastic cells were positive for vimentin and S-100 protein. Based on histopathologic findings and special staining characteristics, this case was diagnosed as chordoma.

Blockade of nitroxidative stress by roasted licorice extracts in high glucose-exposed endothelial cells.

Diabetes can cause a wide variety of vascular complications and endothelial dysfunction. In this study, human vascular endothelial cells were exposed to 5.5 mM and 33 mM glucose for 5 d in the absence and presence of 1 to 20 μg/mL roasted licorice (Glycyrrhiza inflata Bat.) ethanol extracts (rLE). Caspase-3 activation and Annexin V staining revealed that high glucose induced endothelial apoptotic toxicity with a generation of reactive oxygen species (ROS) and these effects were reversed by rLE at ≥1 μg/mL in a dose-dependent manner. Cytoprotective rLE substantially reduced high glucose-induced expression of endothelial nitric oxide synthase (eNOS), and hence attenuated the formation of peroxynitrite radicals derived from NO. In addition, rLE suppressed expression of PKCβ2 and activation of NADPH oxidase subunit of p22phox promoted by high glucose. However, rLE ≤1 μg/mL did not modulate the high glucose-triggered activation of ASK-JNK signaling pathway. Our results suggest that PKCβ2 expression and NADPH oxidase-dependent superoxide production and eNOS-mediated peroxynitrite generation may be essential mechanisms responsible for increased oxidative stress and endothelial apoptosis in chronic hyperglycemic conditions. Thus, rLE may be a beneficial agent most likely contributing to prevention of vascular NADPH oxidase induction and preservation of endothelial nitric oxide availability, resulting in blunting diabetes-associated endothelial dysfunction and vascular complications.