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ABSTRACT: This study investigated the effects of acetyl-L-carnitine (ALC) in secondarily-induced cerebral chronic ischemia models using rats with permanent ligation of bilateral common carotid arteries (BCCL) and spontaneously hypertensive rats (SHR). Additionally, we used normal aged rats as a primary dementia model. Chronic ALC administration at 100 mg/kg (p.o.) for 4 weeks significantly attenuated neurodegenerative changes. In groups receiving 50 mg/kg or 100 mg/kg, ALC inhibited the active astrocyte increase in cerebral tissues of both BCCL and SHR models. In BCCL rats, ALC administration (50 mg/kg or 100 mg/kg, p.o.) resulted in significant promotion of glutathione levels in brain tissues. We also confirmed behavioral improvement after ALC treatment (100 mg/kg for 8 weeks, p.o.) on learning-memory function using aged rats (18 months old) in a passive avoidance task and preservation of CA1 pyramidal neurons was coincided on histopathological observation. In conclusion, chronic ALC administration may ameliorate cerebral ischemia progress after a cerebrovascular disorder as well as spontaneous ageing-related cerebral dysfunction via hippocampal protection.
Archives of Pharmacal Research 01/2012; 35(1):145-54. · 1.59 Impact Factor
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ABSTRACT: Preservation of the cavernous nerves (CNs) during radical prostatectomy is crucial for the patient's erectile function. Despite advances in operative technique, the majority of men report compromised erectile function postprostatectomy or complete loss of potency due to CN trauma even with nerve-sparing modifications.
This study was designed to investigate whether repeated dosing of udenafil, a phosphodiesterase type 5 inhibitor, helps to improve erectile function after CN injury.
Using the CN crush injury model, 8-week-old male Sprague Dawley rats were divided into the following groups; sham-operated group, bilateral CN crush injury exposed to either no udenafil (vehicle) or udenafil (5, 20 mg/kg) daily for two different durations (4 and 8 weeks, p.o.).
At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expressions of hypoxia-inducible factor 1-alpha (HIF-1α), transforming growth factor-beta (TGF-β1), nerve growth factor (NGF), endothelin B receptor (ET(B) ), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sonic hedgehog homolog (SHH) in penile tissue were examined. Immunohistochemical antibody staining was performed for NGF, eNOS, nNOS, CD31, and alpha-smooth muscle actin (α-SMA). Additionally, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay was performed to quantify apoptosis and the tissue slides were stained for Masson's trichrome to assess the smooth muscle/collagen ratio.
Udenafil improved erectile function in a dose- and time-dependent manner with the maximum erectile function recovery achieved by 20 mg/kg udenafil at an 8-week time point. CN injury increased the expression of HIF-1α, TGF-β1, NGF, and ET(B) , however, decreased the expression of eNOS, nNOS, and SHH. Udenafil significantly suppressed these alterations. The results from the histological analyses show that udenafil markedly reduces apoptosis induced by CN injury and augments the smooth muscle/collagen ratio.
CN injury induces significantly impaired erectile function and altered gene/protein expression. Chronic administration of udenafil preserves erectile function and has a beneficial role against the pathophysiological consequences of CN injury.
Journal of Sexual Medicine 03/2011; 8(5):1330-40. · 3.55 Impact Factor
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Jin-Kyu Park,
Il-Hwa Hong,
Mi-Ran Ki,
Hae-Young Chung,
Akihito Ishigami,
Ae-Ri Ji, Moon-Jung Goo,
Dong-Hwan Kim,
Ji-Hoon Kwak,
Chang-Woo Min,
Seung-Sook Lee,
Kyu-Shik Jeong
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ABSTRACT: The binucleation of hepatocytes, which was known as an important feature of liver growth and physiology, has been reported to be increased during the chronic oxidative injury stage and has been regarded as an age-related change of hepatic structures. Therefore, we investigated the binuclearity pattern in the livers of senescence marker proteins-30 (SMP30) knock-out (KO) mice compared with wild-type (WT) mice and vitamin C-treated KO (KO + VC) mice.
The WT, KO and KO + VC mice were fed a vitamin C free diet and VC(+) group mice were given vitamin C water containing 1.5 g/L of vitamin C, whereas VC(-) group was given normal drinking water without vitamin C, for 16 weeks.
In microscopic examination, the livers of KO mice showed a significantly increased number of binuclear hepatocytes compared with that of WT mice and KO + VC mice. KO mice also showed the most increased expression level of CYP2E1 and PCNA determined by immunohistochemistry and immunoblot analysis. Moreover, KO mice indicated the highest level of serum alanine aminotransferase and aspartate aminotransferase level in serum biochemical analysis. Accordingly, significantly decreased levels of reactive oxygen species, MDA (malondialdehyde) and HAE (4-hydroxyalkenals) were detected in KO + VC mice compared with KO mice.
Therefore, it is concluded that vitamin C deficiency induces an increase of CYP2E1 expression and elevated ROS production, which causes oxidative liver injury and the elevation of hepatocyte binucleation in SMP30 KO mice.
Journal of Gastroenterology and Hepatology 11/2010; 25(11):1769-76. · 2.87 Impact Factor
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Mi-Ran Ki, Moon-Jung Goo,
Jin-Kyu Park,
Il-Hwa Hong,
Ae-Ri Ji,
Seon-Young Han,
Sang-Young You,
Eun-Mi Lee,
Ah-Young Kim,
Sang-Joon Park,
Hyun-Joo Lee,
Shin-Yoon Kim,
Kyu-Shik Jeong
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ABSTRACT: Our earlier report has shown that Helicobacter pylori promoted hepatic fibrosis in a murine model. Herein, in order to elucidate the mechanism by which H. pylori accelerate liver fibrosis, the authors investigated the changes in expression levels of mitogen-activated protein kinases (MAPKs), p53-related proteins, antioxidants, and proinflammatory cytokines in liver samples. H. pylori infection enhanced CCl4-induced MAP kinase activation and p53 signaling pathway as well as Bax- and proliferating-cell nuclear antigen expressions, whereas H. pylori alone induced neither of these expressions nor hepatic fibrosis. Moreover, mRNA expressions of inflammatory cytokines, glutathione peroxidase expression, and the proliferative index were strongly augmented in livers of the H. pylori with CCl4 treatment group compared with those of the CCl4-alone treatment group, whereas there was no difference in apoptotic index between the two groups. Interestingly, H. pylori treatment increased the number of α-fetoprotein-expressing hepatocytes independently of CCl4 intoxication. In vitro analyses, using an immortalized rat hepatic stellate cell (HSC) line, revealed that H. pylori lysates increased the proliferation of HSCs, which was boosted by the addition of transforming growth factor-beta1 (TGF-β1). Furthermore, the treatment of H. pylori lysates promoted the translocation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) into the nucleus based on an increase in the degradation of NF-κB inhibitor alpha, in the presence of TGF-β1, as did H2O2 treatment. In conclusion, H. pylori infection along with an elevated TGF-β1 may accelerate hepatic fibrosis through increased TGF-β1-induced pro-inflammatory signaling pathways in HSCs. Moreover, H. pylori infection might increase the risk of TGF-β1-mediated tumorigenesis by disturbing the balance between apoptosis and proliferation of hepatocytes.
Laboratory Investigation 10/2010; 90(10):1507-16. · 3.64 Impact Factor
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Il-Hwa Hong,
Hoon Ji,
Sung-Yong Hwa,
Won-Il Jeong,
Da-Hee Jeong,
Sun-Hee Do,
Ji-Min Kim,
Mi-Ran Ki,
Jin-Kyu Park, Moon-Jung Goo,
Ok-Kyung Hwang,
Kyung-Sook Hong,
Jung-Youn Han,
Hae-Young Chung,
Kyu-Shik Jeong
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ABSTRACT: ENA Actimineral Resource A (ENA-A) is alkaline water that is composed of refined edible cuttlefish bone and two different species of seaweed, Phymatolithon calcareum and Lithothamnion corallioides. In the present study, ENA-A was investigated as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in rats. Liver injury was induced by either subacute or chronic CCl(4) administration, and the rats had free access to tap water mixed with 0% (control group) or 10% (v/v) ENA-A for 5 or 8 weeks. The results of histological examination and measurement of antioxidant activity showed that the reactive oxygen species production, lipid peroxidation, induction of CYP2E1 were decreased and the antioxidant activity, including glutathione and catalase production, was increased in the ENA-A groups as compared with the control group. On 2-DE gel analysis of the proteomes, 13 differentially expressed proteins were obtained in the ENA-A groups as compared with the control group. Antioxidant proteins, including glutathione S-transferase, kelch-like ECH-associated protein 1, and peroxiredoxin 1, were increased with hepatocyte nuclear factor 3-beta and serum albumin precursor, and kininogen precursor decreased more in the ENA-A groups than compared to the control group. In conclusion, our results suggest that ENA-A does indeed have some protective capabilities against CCl(4)-induced liver injury through its antioxidant function.
Marine Biotechnology 10/2010; 13(3):462-73. · 3.43 Impact Factor
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Moon-Jung Goo,
Mi-Ran Ki,
Hye-Rim Lee,
Hai-Jie Yang,
Dong-Wei Yuan,
Il-Hwa Hong,
Jin-Kyu Park,
Kyung-Sook Hong,
Jung-Youn Han,
Ok-Kyung Hwang,
Dong-Hwan Kim,
Sun-Hee Do,
Ronald D Cohn,
Kyu-Shik Jeong
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ABSTRACT: Helicobacter pylori infection has been reported to be very common in patients with chronic liver diseases, including cirrhosis. To elucidate the pathological effect of H. pylori infection on the progression of hepatic fibrosis, C57BL/6 mice and Sprague-Dawley rats were orally inoculated with H. pylori, and hepatic fibrosis was induced with carbon tetrachloride (CCl(4)) administration. We observed the histopathological changes and the presence of H. pylori genes by PCR in the liver. Significant increase in the fibrotic score as well as in serum alanine aminotransferase and aspartate aminotransferase levels was shown in the CCl(4)+H. pylori group compared with that in the CCl(4)-treated group. Compared with the CCl(4)-treated group, alpha-smooth muscle actin and transforming growth factor-beta1 were enhanced; however, senescence marker protein-30, a multifunctional protein protecting hepatocytes against oxidative stress and apoptosis, was suppressed in the CCl(4)+H. pylori group. The 16S rRNA (400 bp) was demonstrated by PCR for H. pylori genes from genomic DNA extracted from the liver, and H. pylori-infected mice showed 93.8% (15 of 16) seropositivity by contrast with seronegativity in all H. pylori-noninfected mice. In addition, immunohistochemical study against H. pylori showed positive antigen fragments in the liver of the infected groups. Consequently, our data suggest that H. pylori infection could be an important contributing infectious factor to the development of liver cirrhosis.
Laboratory Investigation 10/2009; 89(11):1291-303. · 3.64 Impact Factor
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ABSTRACT: The present study reports a case of a 5-month-old female adrenomedullin (AM) heterozygous (+/-) mouse that presented a mass of leiomyosarcoma found in the right shoulder girdle region. The neoplastic mass extended to the sternal region and showed hemorrhages, congestion and necrotic foci. The excised tumor with a diameter of 2.5cm was firm, ill-demarcated and had focally infiltrated the surrounding muscles. The cut surface was homogeneously whitish with multi-focal reddish lesions. Microscopically, the tumor composed of variable fascicles of spindle-shaped cells with pleomorphic and cigar-shaped nuclei. The nuclei were round and elongated. Metastasis of tumor cell to skeletal muscle was frequently observed. Immunohistochemically, desmin, vimentin and alpha-smooth muscle actin (alpha-SMA) were demonstrated in neoplastic cells but tumor cells were negative for cytokeratin (CK) and S-100. Based on gross finding, microscopical examination and immunohistochemistry, the present case was diagnosed as a subcutaneous leiomyosarcoma.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 06/2009; 62(3):221-5. · 1.43 Impact Factor
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Il-Hwa Hong,
Ho-Suk Lee,
Jin-Kyu Park, Moon-Jung Goo,
Dong-Wei Yuan,
Ok-Kyung Hwang,
Kyung-Sook Hong,
Jung-Youn Han,
Ae-Ri Ji,
Mi-Ran Ki,
Kyu-Shik Jeong
Journal of veterinary dentistry 02/2009; 26(2):110-1. · 0.31 Impact Factor
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ABSTRACT: Apoptosis occurs early after irradiation and may be a good indicator of radiation damages. Since elevated levels of TGF-beta are associated with radiation-induced inflammation, the null mice of Smad3, a key downstream mediator of TGF-beta, show accelerated healing of irradiated injury. In order to evaluate resistance to radiation-induced liver injuries in Smad3-null mice, we determined the occurrence of apoptosis and the expression of senescence marker protein-30 (SMP30), as an anti-apoptotic marker, after irradiation to the liver. The livers of Smad3-mutant mice were exposed to local irradiation of 15 gray, from a (60)Co-gamma radiation. One week after irradiation, in Smad3-KO mice, radiation-induced apoptosis was at lower levels compared to those of irradiated WT mice. These findings were well matched with the expression of CYP2E1, which plays a role in hepatic injuries produced by oxidative stress. In addition, antioxidant related protein, the SMP30 levels were reduced by gamma irradiation in both groups. Interestingly, the increased expression of SMP30 expression in Smad3-KO mice liver was preserved at a higher level than that of the WT mice after irradiation. Therefore, these results suggest that the interruption of TGF-beta signaling by deletion of Smad3 brings about inhibition of hepatic apoptosis after ionizing irradiation. Moreover, the protective effect to ionizing radiation might be in correlation with the overexpression of SMP30 in the Smad3-null mice, which may act as an anti-apoptotic signaling molecule. The alteration of SMP30 by interruption of Smad3 might be a useful therapeutic target and diagnostic marker for radiation-induced liver damages.
Journal of Radiation Research 12/2008; 49(6):653-60. · 1.68 Impact Factor
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Moon-Jung Goo,
Mi-Ran Ki,
Hye-Rim Lee,
Il-Hwa Hong,
Jin-Kyu Park,
Hai-Jie Yang,
Dong-Wei Yuan,
Ok-Kyung Hwang,
Sun-Hee Do,
Sung-Eun Yoo,
Kyu-Shik Jeong
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ABSTRACT: We report a case of primary biliary cirrhosis (PBC) that occurred in a 24-month-old male C57BL/6 mouse infected with Helicobacter pylori (H. pylori). Microscopically, the portal tract in the liver showed nonsuppurative destructive cholangitis with variable cytologic distortion of the epithelial cells and peribiliary lymphoplasmacytic infiltration. Immunohistochemistry using alpha-smooth muscle actin demonstrated fibrous bands associating with the wall of vasculature. The level of serum antivacuolating toxin IgG in this mouse showed the highest value (optical density=2.1470) of the H. pylori-infected group (n=13) (optical density=1.7168+/-0.1759, mean+/-SD). Spontaneously developed PBC-like lesions in C57BL/6 mice have been reported by several authors. However, this case strikingly resembles human PBC with its characterized histological features. Therefore, we propose that the increase in vacuolating toxin caused by H. pylori infection may be related to the development of PBC by molecular mimicry.
European journal of gastroenterology & hepatology 11/2008; 20(10):1045-8. · 1.66 Impact Factor
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ABSTRACT: A 1.5-year-old female Persian cat was presented for inappetence and azotemia. Ultrasonography and urography revealed multiple abnormalities involving the genitourinary tract, including agenesis of the right kidney and ureter. Gross examination of the abnormal uterus revealed segmental aplasia of right caudal uterine horn causing cranial distension with fluid, a normal left uterine horn, and both normal ovaries. Microscopically, endometrial glands of the right uterine horn were markedly decreased in number. The right uterine horn was hemorrhagic suggesting estrus. This is the first report of this combination of urinary and uterus abnormalities in the veterinary literature.
Journal of Feline Medicine & Surgery 08/2008; 11(2):153-5. · 1.38 Impact Factor
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Moon-Jung Goo,
Jin-Kyu Park,
Il-Hwa Hong,
Hai-Jie Yang,
Dong-Wei Yuan,
Mi-Ran Ki,
Jung-Youn Han,
Ae-Ri Ji,
Tae-Hwan Kim,
Bruce H Williams,
Kyu-Shik Jeong
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ABSTRACT: A 3-year-old, female Spitz, was presented due to lack of response to therapies with a 6-month history of skin lesions characterized by diffuse erythema and scaling on the dorsal trunk. Physical examination revealed the dog was active and healthy. Skin culture isolated no fungus. Histological examination of skin biopsy specimens revealed interface dermatitis with hydropic degeneration of the basal layers, predominant plasmacytic perivascular accumulation in the dermis, and intensive plasma cell-rich interface mural folliculitis. Moderate CD3-positive lymphocytes infiltrated the superficial dermis. This report may provide unique information of canine discoid lupus erythematosus in an unusual breed with atypical cutaneous lesions.
Journal of Veterinary Medical Science 06/2008; 70(6):633-5. · 0.85 Impact Factor
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Jin-Kyu Park,
Da-Hee Jeong,
Ho-Yong Park,
Kwang-Hee Son,
Dong-Ha Shin,
Sun-Hee Do,
Hai-Jie Yang,
Dong-Wei Yuan,
Il-Hwa Hong, Moon-Jung Goo,
Hye-Rim Lee,
Mi-Ran Ki,
Akihito Ishigami,
Kyu-Shik Jeong
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ABSTRACT: Arazyme is a novel protease produced by the HY-3 strain of Aranicola proteolyticus, which is a Gram-negative aerobic bacterium that has been isolated from the intestine of the spider Nephila clavata. This study focused on the hepatoprotective effect of Arazyme on carbon tetrachloride (CCl4)-induced acute hepatic injury in senescence marker protein 30 (SMP30) knock-out (KO) mice and SMP30 wild-type (WT) mice. WT mice and SMP30 KO mice were divided into eight groups as follows: (i) two negative control groups (G1, G5) which were treated with a single intraperitoneal (i.p.) olive oil injection. (ii) Two positive control groups (G2, G6) which received a single i.p. CCl4 (0.4mL/kg) injection. (iii) Two vitamin C-treated groups (G3, G7) which received a single oral administration of vitamin C (100mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). (iv) Two Arazyme-treated groups (G4, G8) which received a single oral administration of Arazyme (500mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). Through present study, we could find that Arazyme-treated groups showed decreased degree of liver injury, increased expression of SMP30, decreased expression of phospho-Smad3 (p-Smad3), elevated expression of antioxidant proteins including sorbitol dehydrogenase, dihydropteridine reductase (DHPR), dehydrofolate reductase (DHFR), NADH dehydrogenase, glutathione S-transferase kappa 1 (GSTK1) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) compared with non-Arazyme-treated groups. Therefore, it is concluded that Arazyme plays a significant role in protecting injured hepatocytes by increasing the expression of SMP30, inhibiting the transforming growth factor-beta (TGF-beta)/Smad pathway and elevating the expression of antioxidant proteins.
Toxicology 05/2008; 246(2-3):132-42. · 3.68 Impact Factor
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ABSTRACT: Helicobacter pylori vacuolating cytotoxin A (VacA) has been considered as an apoptosis-inducing factor. Here, we investigated the mechanism of VacA-induced apoptosis in relation to the defense mechanism and MAP kinases pathway in gastric epithelial cells. AGS cells exposed to enriched VacA extracts affected the level of SOD-1 and villin. We further investigated the role of VacA in those inductions using a functional recombinant VacA (rVacA). Activation of p38 MAPK and Bax dimerization by rVacA were increased in a dose-dependent manner. rVacA-induced ERK1/2 MAPK activation was maximal at 30 min and 4 h and 1-4 microg/ml of rVacA. rVacA-induced SOD-1 expression was considerably diminished by inhibiting ERK1/2 MAPK and it was slightly increased by inhibiting p38 MAPK. rVacA increased or decreased villin expression depending on dose and exposure time and its expression was mainly appeared in the contractile actin ring of the dividing cells. Despite its cytoprotective effect, SB-203580, a p38 inhibitor, was unlikely to reduce VacA-induced Bax dimerization and rather inhibited villin and Bcl2 expression, indicating that p38 may also play a role in cell proliferation or differentiation for survival after VacA intoxication. Furthermore, p38 inhibitor accelerated rVacA-induced cell death after exposure of AGS cells to H(2)O(2) but ERK1/2 inhibitor protected cells from H(2)O(2) insult. These results suggest that SOD-1 and villin are expressed differentially upon VacA insult depending on dose and exposure time via ERK and p38 MAP kinases; decrease in SOD-1 and villin expression coupled with Bax dimerization leads to apoptosis of gastric epithelial cells.
AJP Gastrointestinal and Liver Physiology 04/2008; 294(3):G635-47. · 3.43 Impact Factor
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ABSTRACT: Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7-10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.
Journal of Veterinary Science 10/2006; 7(3):299-301. · 1.16 Impact Factor
