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Establishment of a murine model for radiation-induced bone loss using micro-computed tomography in adult C3H/HeN mice.

Jin Hee LEE ; Hae June LEE ; Miyoung YANG ; Changjong MOON ; Jong Choon KIM ; Sung Kee JO ; Jong Sik JANG ; Sung Ho KIM

Laboratory Animal Research.2013;29(1):55-62. doi:10.5625/lar.2013.29.1.55

Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (microCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using microCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= -0.071D2-1.799D+18.835 (r2=0.968, D=dose in Gy) and BMD (mg/cm3) = -3.547D2-14.8D+359.07 (r2=0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.
Adult ; Animals ; Biomarkers ; Body Weight ; Bone Density ; Hand Strength ; Humans ; Mice ; Models, Theoretical ; Osteoclasts ; Tibia ; X-Ray Microtomography

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4-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats.

Wook Joon YU ; In Chul LEE ; Jinsoo LEE ; Sang Min LEE ; Sung Hwan KIM ; Hyung Seon BAEK ; Changjong MOON ; Sung Ho KIM ; Yong Hyun CHUNG ; Jong Choon KIM

Laboratory Animal Research.2013;29(1):48-54. doi:10.5625/lar.2013.29.1.48

The present study investigated the potential subacute toxicity of 1,4-dichlorobutane by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male rats at dose levels of 0, 100, 300, and 1,000 mg/kg/day for 4 weeks. All rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry, gross findings, and organ weight were examined. At 1,000 mg/kg/day, an increase in the clinical signs and weights of the liver and kidneys was observed in the male rats. Serum biochemical investigations revealed an increase in alanine aminotransferase, alkaline phosphatase, total cholesterol, total bilirubin, phospholipids, blood urea nitrogen, and gamma glutamyl transferase levels. There were no treatment-related adverse effects in the low and middle-dose groups. In the present experimental conditions, the target organs were determined to be liver and kidney. The no-observed-adverse-effect level was considered to be 300 mg/kg/day in rats.
Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Bilirubin ; Biochemistry ; Blood Urea Nitrogen ; Body Weight ; Cholesterol ; Hematology ; Humans ; Hydrocarbons, Halogenated ; Kidney ; Liver ; Male ; No-Observed-Adverse-Effect Level ; Organ Size ; Phospholipids ; Rats ; Rats, Sprague-Dawley ; Transferases ; Weights and Measures

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Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice.

Sung Hoon PARK ; Seo Na CHANG ; Min Won BAEK ; Dong Jae KIM ; Yi Rang NA ; Seung Hyeok SEOK ; Byoung Hee LEE ; Kyung Sul KIM ; Jae Hak PARK

Laboratory Animal Research.2013;29(1):39-47. doi:10.5625/lar.2013.29.1.39

Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer.
Adenocarcinoma ; Adipose Tissue, White ; Animals ; Humans ; Leptin ; Male ; Mice ; Nucleolus Organizer Region ; Prostate ; Prostatic Neoplasms

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A high resolution genetic mapping of the faded (fe) gene to a region between D10mit156 and D10mit193 on mouse chromosome 10.

Seung Hun OH ; Hajin NAM ; Jun Gyo SUH

Laboratory Animal Research.2013;29(1):33-38. doi:10.5625/lar.2013.29.1.33

The C57BL/6J-fe/fe mouse is a coat color mutant. The coat color of the homozygote mouse becomes progressively lighter with advancing age. The faded gene (fe) of C57BL/6J-fe/fe was mapped in a 2.0 cM distal to D10mit191 by our group. To make a high-resolution map, we used the Korean wild mouse (KWHM) for a backcross panel, which was captured in 1995 and has been maintained as an inbred line by our laboratory. In the inter-specific backcross panel (N=400), the fe gene was mapped to 1.0 cM distal to D10mit156. The gene order was defined: centromere -D10mit3/85 (1.3+/-0.6 cM)-D10mit155 (1.3+/-0.6 cM)-D10mit191 (2.0+/-0.7 cM)-D10mit156 (1.0+/-0.5 cM)-fe-D10mit193 (1.3+/-0.6 cM)-D10mit54 (1.0+/-0.5 cM)-D10mit44 (8.5+/-1.4 cM)-D10mit42 (10.0+/-1.5 cM). The measured distance between D10mit191 and D10mit 44 differed in both inter-specific (DBA/2) and intra-specific (KWHM) backcross panels (14.2 vs 13.8 cM). Taken together, our high-resolution linkage map of the fe locus from an intra-specific backcross panel will provide a good entry point to isolate the fe gene.
Animals ; Centromere ; Chromosomes, Human, Pair 10 ; Gene Order ; Hair Color ; Homozygote ; Mice

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Usefulness of a Helicobacter pylori stool antigen test for diagnosing H. pylori infected C57BL/6 mice.

Dae In MOON ; Eun Hye SHIN ; Hong Geun OH ; Jin Sik OH ; Sunhwa HONG ; Yungho CHUNG ; Okjin KIM

Laboratory Animal Research.2013;29(1):27-32. doi:10.5625/lar.2013.29.1.27

Among several diagnostic tests, a Helicobacter pylori stool antigen (HpSA) test may offer a useful noninvasive method for diagnosing infection without sacrificing animals. In this study, male C57BL/6 mice (n=6) were infected with H. pylori ATCC 49503 (1x10(8) CFU/mouse) by intragastric inoculation three times at 2-day intervals, and H. pylori infected stool specimens were collected 1, 3, 5, 7, 14, 21 days after infection to assess reliability of the HpSA test. Five of six specimens were positive at 5-21 days after infection, and the sensitivity of the HpSA test was 83.33%. The presence of H. pylori infection was confirmed by the rapid urease test and genomic DNA polymerase chain reaction (PCR), and showed the same results as the HpSA. However, the rapid urease test and genomic DNA PCR are invasive tests and require animal sacrifice to detect H. pylori in gastric biopsy samples. We suggest that an HpSA test kit would be useful and effective for monitoring H. pylori in various laboratory animals, as H. pylori can be easily monitored without sacrificing animals.
Animals ; Animals, Laboratory ; Biopsy ; Diagnostic Tests, Routine ; DNA ; Helicobacter ; Helicobacter pylori ; Humans ; Male ; Mice ; Polymerase Chain Reaction ; Urease

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Age-associated changes in pancreatic exocrine secretion of the isolated perfused rat pancreas.

Zheng Er JIANG ; Chengzhe JIANG ; Baihui CHEN ; Chin Su KOH ; Jun Hwan YONG ; Dae Hun PARK ; Moo Ho WON ; Yun Lyul LEE

Laboratory Animal Research.2013;29(1):19-26. doi:10.5625/lar.2013.29.1.19

Gut functions, such as gastrointestinal motility, gastric secretion and pancreatic secretion, were reduced with age. Glucose tolerance is impaired, and the release of insulin and beta-cell's sensitivity on glucose are reduced with age. However, a lot of controversial data have been reported as insulin concentrations after glucose ingestion are either higher or no different in elderly and young subjects. Thus, this study was aimed to investigate whether aging could affect pancreatic exocrine secretion and its action mechanisms. An isolated perfused rat pancreatic model was used to exclude the effects of external nerves or hormones. Pancreatic secretion was increased by CCK under 5.6 mM glucose background in the isolated perfused pancreas of young (3 months), 12 months and 18 months aged rats. There was no significant difference between young and aged rats. In 3 months old rats, CCK-stimulated pancreatic secretion was potentiated under 18 mM glucose background. However, the potentiation effects of endogenous insulin and CCK were not observed in 12 and 18 months old rats. Exogenous insulin also potentiated CCK-stimulated pancreatic secretion in 3 months old rats. Similarly, exogenous insulin failed to potentiate CCK-stimulated pancreatic secretion as that of 3 months old rats. Wet weight of pancreas and amylase content in pancreatic tissue were not changed with age. These results indicate that pancreatic exocrine secretion is reduced with age and endogenous insulin secretion and/or action is involved in this phenomenon.
Aged ; Aging ; Amylases ; Animals ; Cholecystokinin ; Eating ; Gastrointestinal Motility ; Glucose ; Humans ; Insulin ; Pancreas ; Rats

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Stereological study of the diabetic heart of male rats.

Ali NOORAFSHAN ; Hajar KHAZRAEI ; Hossein MIRKHANI ; Saied KARBALAY-DOUST

Laboratory Animal Research.2013;29(1):12-18. doi:10.5625/lar.2013.29.1.12

The present study aimed to quantitatively compare the normal and diabetic hearts of rats using stereological methods. Diabetic and control rats received streptozotocin (60 mg/kg) and no treatments, respectively. On the 56th day, the hearts were removed and their total volume was estimated using isotropic Cavalieri method. The total volume of the connective tissues and vessels, total length and diameter of the vessels, total number of cardiomyocytes nuclei, and the mean volume of the cardiomyocytes were estimated, as well. In comparison to the control animals, 60 and 43% increase was observed in the total volume of the connective tissue and microvessels of the diabetic rats, respectively (P<0.05). The percent of the vessel profiles with the diameter of 2-4 microm was decreased, while the percent of the vessel profiles with the diameter of 4.1-8 microm was increased in the diabetic hearts (P<0.05). No significant difference was found in the vessels with more than 8 microm diameters. The total number of the cardiomyocytes' nuclei and the number-weighted mean volume were respectively decreased by 37 and 64% in the diabetic group (P<0.01). A significant difference was observed between the two groups concerning the left ventricle volume to body weight ratio as an index for ventricular hypertrophy (P<0.05), while no difference was found regarding the right ventricle to body weight ratio. It can be concluded that diabetes can induce structural changes, including loss and/or atrophy of the cardiomyocytes, accompanied with increase in the connective tissue in the rats' hearts.
Animals ; Atrophy ; Body Weight ; Connective Tissue ; Glycosaminoglycans ; Heart ; Heart Ventricles ; Humans ; Hypertrophy ; Male ; Microvessels ; Myocytes, Cardiac ; Rats ; Streptozocin

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Specific nephrotoxicity and cardiotoxicity of BT-CAL(R), Sigma Anti-bonding Molecule Calcium Carbonate, in mice.

Ja Young JANG ; Jingmei CAI ; Jihyun KIM ; Jangbeen KYUNG ; Dajeong KIM ; Ehn Kyoung CHOI ; Youngeun KIM ; Kwang Sei KIM ; Dongsun PARK ; Hyun Gu KANG ; Yun Bae KIM

Laboratory Animal Research.2013;29(1):7-11. doi:10.5625/lar.2013.29.1.7

According to a high anti-osteoporotic efficacy of Sigma Anti-bonding Molecule Calcium Carbonate (SAC), repeated-dose toxicities of SAC were investigated to assess its feasibility as drug or functional food ingredient. Male ICR mice were given drinking water containing 0.006, 0.02 or 0.06% SAC for 4 weeks. SAC feeding decreased the body weights and feed and water consumptions of mice in a dose-dependent manner, especially, leading to severe emaciation and 70% death in 3 weeks in the high-dose (0.06%) group. Not only kidney and heart weights, but also the levels of blood urea nitrogen, creatinine, aspartate transaminase, and creatine phospokinase significantly increased after SAC administration, indicative of nephrotoxicity and cardiotoxicity. Such renal and cardiac toxicities were also confirmed by microscopic findings, exhibiting renal crystals and cardiac fibrosis, which may be due to the insoluble crystal formation and calcium overload, respectively. In conclusion, it is suggested that no observed adverse effect level of SAC is lower than 0.006% in mice, and that a long-term intake may cause serious adverse effects on renal and cardiac functions.
Animals ; Aspartate Aminotransferases ; Blood Urea Nitrogen ; Body Weight ; Calcium ; Calcium Carbonate ; Creatine ; Creatinine ; Drinking Water ; Emaciation ; Fibrosis ; Functional Food ; Heart ; Humans ; Kidney ; Male ; Mice ; Mice, Inbred ICR ; No-Observed-Adverse-Effect Level ; Weights and Measures

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Serum leptin concentrations, leptin mRNA expression, and food intake during the estrous cycle in rats.

Wirasak FUNGFUANG ; Tomoaki NAKADA ; Nobuhiro NAKAO ; Misao TERADA ; Makoto YOKOSUKA ; Sveinbjorn GIZURARSON ; Jann HAU ; Changjong MOON ; Toru R SAITO

Laboratory Animal Research.2013;29(1):1-6. doi:10.5625/lar.2013.29.1.1

The aim of this study was to investigate food intake, serum leptin levels, and leptin mRNA expression during the sexual cycle in rats. Female Wistar-Imamichi rats aged 8-10 weeks were used in this experiment. Food intake was measured during the light and dark phases (light on at 07:00 and off at 19:00) of the 4-day estrous cycle in female rats. Serum leptin levels were measured by ELISA, and leptin mRNA expression levels were analyzed using real-time PCR on diestrous- and proestrous-stage rats. Our results revealed that during the sexual cycle, food intake was significantly higher in the dark phase compared with the light phase. Food intake in proestrous females was significantly lower in the light and dark phases compared with the other groups. Serum leptin concentrations were significantly higher in both phases in proestrous rats compared with diestrous rats. There was a significant increase in leptin mRNA expression in adipose tissue during the proestrous period compared with the diestrous period. These findings suggest that increased leptin mRNA expression and serum leptin levels, which are induced by estrogen during the proestrous stage, may play a role in regulating appetitive behavior.
Adipose Tissue ; Aged ; Animals ; Appetitive Behavior ; Eating ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; Estrous Cycle ; Female ; Humans ; Leptin ; Light ; Rats ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

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HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide.

Na Rae SHIN ; Sung Ho KIM ; Je Won KO ; Sung Hyeuk PARK ; In Chul LEE ; Jung Min RYU ; Jong Choon KIM ; In Sik SHIN

Laboratory Animal Research.2017;33(1):40-47. doi:10.5625/lar.2017.33.1.40

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.
Animals ; Cell Count ; Immune System ; Inflammation* ; Interleukins ; Lung ; MAP Kinase Signaling System ; Matrix Metalloproteinase 9 ; Mice ; Phosphorylation ; Plant Preparations* ; Pneumonia ; Pulmonary Disease, Chronic Obstructive ; Receptors, Tumor Necrosis Factor ; Smoke* ; Therapeutic Irrigation ; Tobacco Products*

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