A renal oncocytoma in a Maltese dog with renal cysts / 대한수의학회지

A renal oncocytoma was diagnosed in an 8-year-old female Maltese dog with a history of renal cysts. Tumor cells were not detected until six months after observation of renal cysts. Nephrectomy was performed to treat the neoplasia. Tumor-like masses with numerous nodules were observed in the inner surface of cysts present in the caudal part of the left kidney. Histologically, the tumor consisted of cells with abundant eosinophilic cytoplasm. The diagnosis was based on histological features, periodic acid-Schiff reaction, and immunohistochemical cytokeratin staining. Based on a literature review, this is the first canine renal oncocytoma case reported in Korea.

A renal oncocytoma in a Maltese dog with renal cysts

A renal oncocytoma was diagnosed in an 8-year-old female Maltese dog with a history of renal cysts. Tumor cells were not detected until six months after observation of renal cysts. Nephrectomy was performed to treat the neoplasia. Tumor-like masses with numerous nodules were observed in the inner surface of cysts present in the caudal part of the left kidney. Histologically, the tumor consisted of cells with abundant eosinophilic cytoplasm. The diagnosis was based on histological features, periodic acid-Schiff reaction, and immunohistochemical cytokeratin staining. Based on a literature review, this is the first canine renal oncocytoma case reported in Korea.

Effects of neural stem cells and 5-fluorocytosine in canine metastatic lung tumor

This is the first case report to describe the tumor regressive effect of systemic human neural stem cell (NSC)/5-fluorocytosine (5-FC) therapy on canine metastatic lung tumor. The therapeutic effects appeared approximately two weeks after 5-FC administration. Thoracic radiographs revealed a reduced number of lung nodules and decreased nodule size. However, there were no significant antitumor effects on primary lesions in abdominal organs. In conclusion, human NSC/5-FC prodrug therapy can secure patient quality of life with the same or more therapeutic effects and fewer side effects than other recommended chemotherapies.

Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.

Chemopreventive effect of alpha-viniferin in azoxymethane-induced mouse colorectal tumor and Caco-2 cells / 동물의과학연구지

alpha-Viniferin (AVF), a trimer of resveratrol, is known to have an anti-inflammatory effect via inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). It has been reported that up-regulated COX-2 and iNOS are expressed in colon cancer tissues of humans and rodents as well as pre-neoplastic aberrant crypt foci (ACF) of rodents. In this study, chemopreventive effects of AVF were assessed in Caco-2 cells as well as azoxymethane (AOM)-induced colorectal tumorigenesis in mice. Anti-tumor effect of AVF with regards to apoptotic induction was assessed by TUNEL and caspase-3 expression in human colon cancer Caco-2 cells. For development of ACF, AOM was administered with to mice intraperitoneally at a dose of 10 mg/kg once a week for 3 weeks. To induce colitis-related colon cancer, mice were administered a single dose of AOM (10 mg/kg) and 2% dextran sodium sulfate in drinking water. Mice treated with 0.05 and/or 0.1 mg of AVF by gavage showed significantly reduced development of ACF and colorectal tumors. Immunofluorescence detection in Caco-2 cells showed reduced COX-2 and iNOS expression, whereas cleavage of caspase-3 and apoptotic cell numbers increased upon AVF treatment. Immunostaining showed reduced expression levels of COX-2 and iNOS expression along with increased cleaved caspase-3 expression increased upon AVF treatment. These results suggest that AVF has chemopreventive effects on colorectal cancer via anti-inflammatory potential and pro-apoptotic activity.

Chemopreventive effects of garlic and mugwort mixture extract on Helicobacter pylori-associated mouse gastric carcinogenesis / 대한수의학회지

Garlic and mugwort have long been used in traditional medicine to prevent various diseases. Several in vitro studies have reported protective efficacies of garlic and mugwort in cases of gastric cancer. In the present study, we investigated the cancer preventive effects of garlic and mugwort mixture extract (GME) in a Helicobacter (H.) pylori-associated gastric carcinogenesis mouse model. To induce gastric cancer, C57BL/6 mice were treated with N-methyl-N-nitrosourea and H. pylori. Various concentrations of GME (0, 100, 500, and 1,000 ppm) were then fed to the mice for 38 weeks, after which the tumor tissues were examined for histopathology, mucin histochemistry and beta-catenin. The incidence of gastric tumors was significantly lower in the highest dose GME-treated mice (46.7%) than control mice (85.7%) (p < 0.05). The multiplicity and size of tumors were also significantly reduced by GME feeding in a dose-dependent manner (p < 0.01). Furthermore, GME suppressed the H. pylori-associated chronic inflammation measured by histologic grading of H. pylori density, chronic gastritis, glandular atrophy and intestinal metaplasia in non-tumorous gastric mucosae. Our data suggest that GME suppresses gastric tumorigenesis via suppression of H. pylori-associated chronic inflammation.

Chemopreventive effects of garlic and mugwort mixture extract on Helicobacter pylori-associated mouse gastric carcinogenesis / 대한수의학회지

Garlic and mugwort have long been used in traditional medicine to prevent various diseases. Several in vitro studies have reported protective efficacies of garlic and mugwort in cases of gastric cancer. In the present study, we investigated the cancer preventive effects of garlic and mugwort mixture extract (GME) in a Helicobacter (H.) pylori-associated gastric carcinogenesis mouse model. To induce gastric cancer, C57BL/6 mice were treated with N-methyl-N-nitrosourea and H. pylori. Various concentrations of GME (0, 100, 500, and 1,000 ppm) were then fed to the mice for 38 weeks, after which the tumor tissues were examined for histopathology, mucin histochemistry and beta-catenin. The incidence of gastric tumors was significantly lower in the highest dose GME-treated mice (46.7%) than control mice (85.7%) (p < 0.05). The multiplicity and size of tumors were also significantly reduced by GME feeding in a dose-dependent manner (p < 0.01). Furthermore, GME suppressed the H. pylori-associated chronic inflammation measured by histologic grading of H. pylori density, chronic gastritis, glandular atrophy and intestinal metaplasia in non-tumorous gastric mucosae. Our data suggest that GME suppresses gastric tumorigenesis via suppression of H. pylori-associated chronic inflammation.

Elm tree bark extract inhibits HepG2 hepatic cancer cell growth via pro-apoptotic activity

Control of inflammation is widely accepted as an important strategy for cancer chemoprevention. Anti-inflammatory effects of bark extracts of elm tree (BEE) have been amply reported. Therefore, BEE may be a good candidate cancer chemopreventive agent. Considering the high incidence of hepatic cancer and limited therapeutic approaches for treating this disease, it is important to develop liver cancer-specific chemopreventive agents. To evaluate the chemopreventive potential of BEE, we investigated the growth inhibition effect of BEE on the HepG2 human hepatocellular carcinoma cell line. We performed a cell counting kit-8 assay to determine cell viability, and 4,6-diamino-2-phenylindole staining and flow cytometry to measure apoptotic cell death. Finally, the expression levels of pro- and anti-apoptotic proteins were measured. BEE inhibited the growth of HepG2 cells and induced apoptosis in a dose-dependent manner. Pro-apoptotic activity was promoted via the mitochondrial pathway of apoptosis, as demonstrated by the activation of pro-apoptotic proteins Bax, caspase-9, caspase-3, and poly (ADP-ribose) polymerase as well as the down-regulation of the anti-apoptotic protein Bcl-2. These results suggest that BEE may have potential use in hepatic cancer chemoprevention by suppressing cancer cell growth via pro-apoptotic activity.

Increased Nephrotoxicity after Combined Administration of Melamine and Cyanuric Acid in Rats / 한국실험동물학회지

Renal toxicity by melamine in combination with cyanuric acid (1:1) was investigated. Male rats were orally administered melamine plus cyanuric acid (5, 50 or 400 mg/kg each) for 3 days. In contrast to a negligible effect by melamine alone (50 mg/kg, a no-observed-adverse-effect-level: NOAEL), co-administration with cyanuric acid markedly increased the concentrations of blood urea nitrogen and creatinine, as well as kidney weight. A high dose (400 mg/kg) of melamine plus cyanuric acid induced more severe kidney toxicity. The increased blood parameters for kidney toxicity and organ weight lasted longer than 4 days. Combined treatment with melamine and cyanuric acid (50-400 mg/kg each) resulted in many gold-brown crystals and toxic lesions in renal tubules, which were not observed in animals treated with melamine alone (50 mg/kg). These results indicate that only a 3-day exposure to melamine in combination with cyanuric acid causes severe renal damage, even at a NOAEL for melamine found in a 13-week toxicity study. Therefore, it is suggested that the tolerable daily intake or regulatory/management levels of melamine need to be re-considered for cases of co-exposure with cyanuric acid.

A survey of traumatic reticular diseases in Korea and the effects on beef quality grade / 대한수의학회지

This study surveyed the prevalence of traumatic reticular diseases (TRD) of slaughter cattle in Korea, the typology of the causative foreign bodies and the effects on beef quality and carcass weight. The overall prevalence of TRD in 3,121 slaughter cattle was 5.5%. However, the prevalence was significantly higher in Korea indigenous cattle Hanwoo (5.8%, p < 0.05) and female cattle (20.75%, p < 0.001). The prevalence significantly increased in aged cattle (p < 0.001). Major lesions related to foreign bodies were reticulitis (96%) and peritonitis (86%). Most causative foreign bodies were made of iron including nails, wires, steel rods, screw nails, and syringe needles. Cattle affected with TRD produced significantly lower grade quality of beef compared to normal cattle (p < 0.0001), but TRD did not affect carcass weight. The data will be useful in the management of TRD, with the aim of increasing beef productivity in Korea.

A Tumoral Calcinosis Case in a Beagle Dog / 한국실험동물학회지

We describe a case of tumoral calcinosis in a 13-month-old female Beagle dog presenting for surgical removal of a 4x3x3 cm mass in the soft tissues of the medial right shoulder joint. On radiologic examination, the mass showed increased radiopacity. Blood analysis data indicated chronic renal failure with hyperphosphatemia and hypercalcemia. Grossly, the mass was irregular, round and multilocular, with hard consistency. Histologically, there were many variable-sized loculi surrounded by capsule and interstitial connective tissues were generated among the loculi. Inflammatory cells, fibroblasts, fibrocytes and multinucleated giant cells were present at the margins of the loculi. Most of the loculi were filled with calcium or chalky material. To our knowledge, this is the first case of tumoral calcinosis in Korea.

Modifying Effect of Indole-3-carbinol on the Rat Colon Carcinogenesis / 한국실험동물학회지

Indole-3-carbinol (I3C) found in various cruciferous vegetables has been shown to exert anti-carcinogenic activity in several target organs. Our study was conducted to assess the modifying effect of I3C on the development of colon tumor induced by azoxymethane (AOM). Eighty-seven male F344 rats were divided into 5 groups and were treated with AOM followed by I3C 100 or 300 ppm, AOM alone, I3C alone, and non-treatment, respectively. The animals were subcutaneously injected with AOM. Then diet containing I3C were fed to the rats for 37 weeks. All rats were sacrificed at 40 weeks. Liver and kidney weights of rats treated with I3C at doses of 100 or 300 ppm were significantly increased compared to those of the control group. Colonic tumor incidence and multiplicity of rats treated with I3C at doses of 100 and 300 ppm were not significant compared to those of AOM alone group. In the pathological examination, most of tumors were classified with adenoma and adenocarcinoma in the small and large intestine. These results demonstrated that I3C may have not chemopreventive effect on the rat colon carcinogenesis.

The inhibitory effect of quercitrin gallate on iNOS expression induced by lipopolysaccharide in Balb/c mice

Quercetin 3-O-beta-(2''-galloyl)-rhamnopyranoside (QGR) is a naturally occurring quercitrin gallate, which is a polyphenolic compound that was originally isolated from Persicaria lapathifolia (Polygonaceae). QGR has been shown to have an inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Therefore, this study was conducted to investigate the inhibitory effect of QGR on nitric oxide production and inducible nitric oxide synthases (iNOS) expression in LPS-stimulated Balb/c mice. To accomplish this, 10 mg/kg of QGR was administered via gavage once a day for 3 days. iNOS was then induced by intraperitoneal injection of LPS. Six hours after the LPS treatment the animals were sacrificed under ether anethesia. The serum levels of NO were then measured to determine if QGR exerted an inhibitory effect on NO production in vivo. LPS induced an approximately 6 fold increase in the expression of NO. However, oral administration of QGR reduced the LPS induced increase in NO by half. Furthermore, RT-PCR and western blot analysis revealed that the increased levels of iNOS expression that occurred in response to treatment with LPS were significantly attenuated in response to QGR pretreatment. Histologically, LPS induced the infiltration of polymorphonuclear neutrophils in portal veins and sinusoids and caused the formation of a large number of necrotic cells; however, pretreatment with QGR attenuated these LPS induced effects. Taken together, these results indicate that QGR inhibits iNOS expression in vivo as well as in vitro and has antiinflammatory potentials.

Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase(PHGPx), an antioxidative selenoprotein, is modulated byestrogen in the testis and oviduct. To examine whetherpotential endocrine disrupting chemicals (EDCs) affectthe microenvironment of the testes, the expression patternsof PHGPx mRNA and histological changes were analyzedin 5-week-old Sprague-Dawley male rats exposed to severalEDCs such as an androgenic compound [testosterone (50,200, and 1,000microg/kg)], anti-androgenic compounds [flutamide(1, 5, and 25mg/kg), ketoconazole (0.2 and 1mg/kg), anddiethylhexyl phthalate (10, 50, and 250mg/kg)], andestrogenic compounds [nonylphenol (10, 50, 100, and 250mg/kg), octylphenol (10, 50, and 250mg/kg), and diethyl-stilbestrol (10, 20, and 40microg/kg)] daily for 3 weeks via oraladministration. Mild proliferation of germ cells andhyperplasia of interstitial cells were observed in the testesof the flutamide-treated group and deletion of thegerminal epithelium and sloughing of germ cells wereobserved in testes of the diethylstilbestrol-treated group.Treatment with testosterone was shown to slightly decreasePHGPx mRNA levels in testes by the reverse transcription-polymerase chain reaction. However, anti-androgeniccompounds (flutamide, ketoconazole, and diethylhexylphthalate) and estrogenic compounds (nonylphenol,octylphenol, and diethylstilbestrol) significantly up-regulated PHGPx mRNA in the testes (p<0.05). Thesefindings indicate that the EDCs might have a detrimentaleffect on spermatogenesis via abnormal enhancement ofPHGPx expression in testes and that PHGPx is useful as abiomarker for toxicity screening of estrogenic or anti-androgenic EDCs in testes.