Seong-Soo Kang

The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats

This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-κB) and phosphorylation of I kappaB alpha (IκBα) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-κB translocation and IκBα phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-κB activation.

Maternal Exposure to Multi-Wall Carbon Nanotubes Does Not Induce Embryo-Fetal Developmental Toxicity in Rats

BACKGROUNDnAlthough the potential risk of carbon nanotubes (CNTs) to humans has recently increased due to expanding production and widespread use, the potential adverse effects of CNTs on embryo-fetal development have not yet been determined.nnnMETHODSnThis study investigated the potential effects of multi-wall CNTs (MWCNTs) on pregnant dams and embryo-fetal development in rats. MWCNTs were administered to pregnant rats by gavage at 0, 40, 200, and 1,000 mg/kg/day. All dams were subjected to Cesarean section on day 20 of gestation, and the fetuses were examined for any morphological abnormalities.nnnRESULTSnAll animals survived to the end of the study. A decrease in thymus weight was observed in the high dose group in a dose-dependent manner. However, maternal body weight, food consumption, and oxidant-antioxidant balance in the liver were not affected by treatment with MWCNTs. No treatment-related differences in gestation index, fetal deaths, fetal and placental weights, or sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in incidences of abnormalities between the groups.nnnCONCLUSIONSnThe results show that repeated oral doses of MWCNTs during pregnancy induces minimal maternal toxicity and no embryo-fetal toxicity at 1,000 mg/kg/day in rats. The no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1,000 mg/kg/day for embryo-fetal development. In this study, the dosing formulation was not analyzed to determine the degree of reaggregation (or not), nor were blood levels of CNTs measured in the dosed animals to verify or characterize absorption.

Biocompatibility of Mineral Trioxide Aggregate Mixed with Hydration Accelerators

INTRODUCTIONnThe aim of this study was to evaluate the biocompatibility of mineral trioxide aggregate mixed with selective hydration accelerators such as calcium chloride (CaCl2), citric acid (CA), and calcium lactate gluconate solution (CLG).nnnMETHODSnInductively coupled plasma-atomic emission spectrometry analysis was used to measure calcium ions in the extracts of test materials. The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide assay was performed using MG-63 cells to examine the cytotoxicity of the test materials. The surface of each sample and the growth pattern of the attached cells were observed using scanning electron microscopy (SEM).nnnRESULTSnMTA mixed with 10 wt% CaCl2 and MTA mixed with 43.4 wt% CLG released a higher amount of calcium ions than the other groups. The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide assay revealed that the cell viability of MTA mixed with 0.1 wt% CA was significantly higher than pure MTA on 7-day extract (P < .05). MTA mixed with 43.4 wt% CLG showed significantly higher cell viability than the other groups on 1-day extract (P < .05). MTA mixed with 10 wt% CaCl2 in all groups showed the lowest cell viability at all time points (P < .05). Under SEM, elongated and confluent cells were observed in all samples except in samples of MTA mixed with 10 wt% CaCl2.nnnCONCLUSIONSnMTA mixed with 0.1 wt% CA showed good biocompatibility. MTA mixed with 43.4 wt% CLG showed favorable biocompatibility on 1 day. MTA mixed with 10 wt% CaCl2 in all groups showed the lowest cell viability at every time point and poor cell attachment under SEM.

Sequential delivery of BMP-2 and BMP-7 for bone regeneration using a heparinized collagen membrane.

To investigate the effect of the sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 on bone regeneration in rat calvarial defects (40 Sprague-Dawley rats, 8mm defect size), all animals were treated with a hydroxyapatite (HA)/tricalcium phosphate (TCP) bone graft covered with a collagen membrane. The experimental groups were as follows: (1) control group: unmodified collagen (no treatment); (2) BMP-2 group: 5 μg of BMP-2; (3) hep-BMP-7 group: 5 μg BMP-7 chemically bound to heparinized collagen; and (4) BMP-2/hep-BMP-7 group: 2.5 μg BMP-7 bound to heparinized collagen and subsequently treated with 2.5 μg BMP-2. Defect healing was examined at 2 and 8 weeks after surgery. The BMP-2 group showed the largest new bone area at week 2 (29.3 ± 7.3%; P = 0.009); new bone areas in the hep-BMP-7 and BMP-2/hep-BMP-7 groups were similar (11.8 ± 3.4% and 12.9 ± 5.71%, respectively; P = 0.917). After 8 weeks, the BMP-2/hep-BMP-7 group showed the largest new bone area (43.3 ± 6.2%), followed by the BMP-2 and hep-BMP-7 groups (P = 0.013). Accordingly, in comparison with single deliveries of BMP-2 and BMP-7, sequential delivery of BMP-2 and BMP-7 using a heparinized collagen membrane significantly induced new bone formation with a smaller quantity of BMP-2 in rat calvarial defects.

The effect of rhBMP-2 and PRP delivery by biodegradable β-tricalcium phosphate scaffolds on new bone formation in a non-through rabbit cranial defect model

This study evaluated whether the combination of biodegradable β-tricalcium phosphate (β-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. β-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16xa0weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated β-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated β-TCP scaffolds (Pxa0<xa00.05). Although new bone was higher than adjacent bone at 8xa0weeks after implantation, vertical bone augmentation was not observed at 16xa0weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.

Cloning and expression of the sucrose phosphorylase gene from Leuconostoc mesenteroides in Escherichia coli

The gene encoding sucrose phosphorylase (742sp) in Leuconostoc mesenteroides NRRL B-742 was cloned and expressed in Escherichia coli. The nucleotide sequence of the transformed 742sp comprised an ORF of 1,458xa0bp giving a protein with calculated molecular mass of 55.3xa0kDa. 742SPase contains a C-terminal amino acid sequence that is significantly different from those of other Leu. mesenteroides SPases. The purified 742SPase had a specific activity of 1.8xa0U/mg with a Km of 3xa0mM with sucrose as a substrate; optimum activity was at 37°C and pH 6.7. The purified 742SPase transferred the glucosyl moiety of sucrose to cytosine monophosphate (CMP).

The effect of bacterial cellulose membrane compared with collagen membrane on guided bone regeneration

PURPOSE This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (α<.05). RESULTS BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane.

26-Week repeated oral dose toxicity study of the new quinolone antibacterial DW-116 in Sprague–Dawley rats

The purpose of this study is to investigate the potential subchronic toxicity of DW-116 by a 26-week repeated oral dose in Sprague-Dawley rats. The test article, DW-116, was administered daily by gavage to male and female rats at dose levels of 0, 5, 25 and 125 mg/kg/day. At the end of the treatment period, 12 rats/sex/group were sacrificed, while six extra rats/sex in the vehicle control and highest dose groups were sacrificed after a 4-week recovery. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. There was no treatment-related mortality. An increase in the incidence of post-dosing salivation was observed in both sexes of the highest dose group. At the scheduled autopsy, an increase in the liver weight was observed in males of the highest dose group in a dose-dependent manner. Hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) and lymphocyte counts in males treated with the 125 mg/kg dose. Total bilirubin and alanine aminotransferase (ALT) values were also increased in males at the same dose. These effects were completely reversible during the recovery period. There were no adverse effects on body weight, food and water consumption, ophthalmoscopy, urinalysis, necropsy findings and histopathology in any treatment group. Based on these results, it was concluded that the 26-week repeated oral dose of DW-116 caused increases in the liver weight, WBC counts, total bilirubin and ALT values in males at a dose level of 125 mg/kg/day. The target organ was determined to be the liver and WBC in males, but not in females. The no-observed-adverse-effect level (NOAEL) was considered to be 25 mg/kg/day for males and 125 mg/kg/day for females.

Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats.

We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological alterations, including degeneration/necrosis of hepatocytes, vacuolation, and sinusoidal dilation. In addition, an increase in the malondialdehyde (MDA) concentration and a decrease in the reduced glutathione (GSH) content and catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities were observed in the cisplatin-treated rat hepatic tissues. In contrast, PYC treatment effectively prevented cisplatin-induced hepatotoxicity, including the elevation of aminotransferase and histopathological lesions, in a dosedependent manner. Moreover, PYC treatment also induced antioxidant activity by decreasing MDA level and increasing GSH content and SOD and GST activities in liver tissues. These results indicate that PYC has a protective effect against acute hepatotoxicity induced by cisplatin in rats, and that the protective effects of PYC may be due to inhibiting lipid peroxidation and increasing antioxidant activity.

Effects of Dietary Supplementation of a New Probiotic CS61 Culture on Performance in Broiler Chickens

Bacterial resistance to antibiotics and residues of antibiotics in poultry products have encouraged the use of probiotics, prebiotic substrates, and synbiotic combinations of prebiotics and probiotics as alternative approaches to the use of antibiotics in poultry. The present study was carried out to evaluate the effect of a new probiotic CS61 culture on growth performance, feed conversion efficiency, and safety in broiler chickens, and to evaluate its value as an alternative for antibiotics used as a feed additive. Two dosages of CS61 culture (0.1% and 1%) were fed to chickens for 28 days. The results showed that terminal body weight and daily weight gain in the treatment groups increased in a dose-dependent manner when compared with the control group. Dietary supplementation with CS61 culture also improved feed conversion rate compared to the control group. There were no treatment- related toxic effects in terms of clinical findings, mortality, necropsy findings, hematology, or serum biochemistry parameters in any group tested. The nitric oxide assay showed that CS61 peptide has a dose-dependent inhibitory effect on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. The results of this experiment indicated that dietary supplementation of CS61 culture may improve growth performance and feed conversion efficiency in chickens through its anti-inflammatory effect.