• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.635-640
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• 1992

Two cases of lingual masses were observed among 500 Fischer 344 (F344) rats which were used as control and treated animals in a 2 year carcinogenicity study in Toxicology Research Center, Korea Research Institute of Chemical Technology. The masses grossly appeared as tan, pedunculated, fungiform on the dorsal aspect of the base of the tongues. They were approximately $1.5{\times}1.2{\times}0.3cm$ in size. The microscopic features consisted of acanthosis, hyperkeratosis, papillary projection with connective tissue cores and multifocal chronic active inflammation with hair shafts. The results observed support the epigenetic mechanism of tumorigenesis which is caused by Physical stimuli of foreign bodies. Both of the masses were diagnosed as papillomas with the incidence rate of 0.4%(1/250) in each sex on the basis of the gross and microscopic features.

• Biomolecules & Therapeutics
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• v.10 no.3
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• pp.193-199
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• 2002

The arylamine N-acetyltransferases (NATs) are a family of enzymes that N-acetylate mylhydrazines and arylamines through transfer of an acetyl group from acetyl coenzyme A. This activity was found to vary among individuals as a Mendalian trait and the basis of the genetic differences in human NAT activity is one of the best of the genetic studied examples of pharmacogenetic variation. The classical N-acetylation polymorphism is regulated at the NAT2 locus, which segregates individuals into rapid, intermediate, and slow acetylator phenotypes. In this study, the relationship between NAT2 activity phenotype using HPLC:UV assay for the determination of dapsone and monoacetyldapsone in plasma and NAT2 genotype by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was investigated in the F2 hybrid (Fischer 344 vs Wistar-Kyoto) rats. Three Common mutant alleles at the NAT2 gene locus have been identified in the F2 generation progeny of Fischer 344 rats as raid acetylator and Wistar-Kyoto rats as slow acetylator segregated into three modes (low, intermediates, and high) with simple Mendelian inheritance. The metabolic activity of NAT2 of the intermediate and rapid acetylators is significant1y greater than slow acetylator, but the metabolic activity of rapid acetylator is not significantly different from Intermediate type. Therefore, we could observe that complete trimodal NAT2 genotypic alleles and incomplete trimodal NAT2 metabolic phenotypic distribution in tile F2 hybrid rats. These observations suggest that the relationships between NAT2 genotype and metabolic phenotype exists and F2 hybrid (Fischer 344: Wistar-Kyoto) animal models about NAT2 polymorphism might be applied in the toxicity and pharmacogenetic studies of arylamine drugs and carcinogens.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.547-553
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• 2004

The pyrrolizidine alkaloids (PAs), contained in a number of traditional remedies in Africa and Asia, show wide variations in metabolism between animal species but little work has been done to investigate differences between animal strains. The metabolism of the PA senecionine (SN) in Fischer 344 (F344) rats has been studied in order to compare to that found in the previously investigated Sprague-Dawley (SO) rats (Drug Metab. Dispos. 17: 387, 1989). There was no difference in the formation of ($\pm$) 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, bioactivation) by hepatic microsomes from either sex of SO and F344 rats. However, hepatic microsomes from male and female F344 rats had greater activity in the Noxidation (detoxication) of SN by 88% and 180%, respectively, when compared to that of male and female SD rats. Experiments conducted at various pH showed an optimum pH of 8.5, the optimal pH for flavin-containing monooxygenase (FMO), for SN N-oxidation by hepatic microsomes from F344 females. In F344 males, however, a bimodal pattern was obtained with activity peaks at pH 7.6 and 8.5 reflecting the possible involvement of both cytochrome P450 (CYP) and FMO. Use of specific inhibitors (SKF525A, 1-benzylimidazole and methimazole) showed that the N-oxide of SN was primarily produced by FMO in both sexes of F344 rats. In contrast, SN N-oxide formation is known to be catalyzed mainly by CYP2C11 rather than FMO in SD rats. This study, therefore, demonstrated that there were substantial differences in the formation of SN N-oxide by hepatic microsomes from F344 and SD rats and that this detoxification is catalyzed primarily by two different enzymes in the two rat strains. These findings suggest that significant variations in PA biotransformation can exist between different animal strains.

• Korean Journal of Veterinary Research
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• v.48 no.4
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• pp.401-411
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• 2008

This study was performed to evaluate repeated-dose oral toxicities of Flos lonicerae extract in Fischer 344/n rats. Flos lonicerae was administered orally to rats at dose levels of 0, 37, 111, 333, 1,000 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Flos lonicerae extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program and The Standards of Toxicity Study for Medicinal Products. In the present study, there were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Flos lonicerae extract. These results suggest that the oral no observed adverse-effect level of the test item, Flos lonicerae extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.

• Korean Journal of Veterinary Research
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• v.49 no.1
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• pp.23-34
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• 2009

This study was performed to evaluate repeated-dose oral toxicities of Chelidonium majus extract in Fischer 344/N rats. Chelidonium majus extract was administered orally to rats at dose levels of 0, 25, 74, 222, 666 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Chelidonium majus extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program (issued by National Institute of Toxicological Research) and The Standards of Toxicity Study for Medicinal Products (issued by Korea Food and Drug Administration). In the present study, There were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Chelidonium majus extract. These results suggest that the oral no observed adverse-effect level of the test item, Chelidonium majus extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.470-476
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• 2010

The resistant dextrin NUTRIOSE$^{(R)}$, developed from starch, is expected to act as a prebiotic. The aim of this study was to determine the effects of NUTRIOSE$^{(R)}$ on cecal parameters, short-chain fatty acid (SCFA) concentrations, and fecal excretion in rats. In an initial experiment, twenty-four male Fischer F344 rats were randomly assigned to one of the following four treatments for 14 days: G0 (control diet), G2.5 (control diet+2.5% of dextrin), G5 (control diet + 5% of dextrin), and G10 (control diet + 10% of dextrin). After 14 days, total cecal weight, cecal content, and cecal wall weight were significantly increased in G5 and G10 compared to G0. At the same time, cecal pH was significantly lower in G10 compared to G0. Total SCFA concentration was significantly higher in G10 than in G5, G2.5, and G0, and significantly higher in G5 than in G0. Acetate, butyrate, and propionate concentrations were significantly increased in G5 and G10 compared to the controls. In a second trial based on a similar design, eighteen male Fischer F344 rats were treated with a control diet supplemented with 5% of dextrin or 5% of fructo-oligosaccharide. The results obtained with NUTRIOSE$^{(R)}$ were similar to those obtained with the fructo-oligosaccharide. In a third experiment, two groups of 5 Fischer F344 rats were orally treated with 100 and 1,000 mg/kg NUTRIOSE$^{(R)}$, respectively, and from 18% to 25% of the dextrin was excreted in the feces. The results of these three studies show that the consumption of NUTRIOSE$^{(R)}$, by its effects on total cecal weight, cecal content, cecal wall weight, pH, and SCFA production, could induce healthy benefits since these effects are reported to be prebiotic effects.

• Journal of Environmental Health Sciences
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• v.22 no.3
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• pp.17-27
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• 1996

The purpose of this study was to evaluate the decreasing effects of Korean garlic against the accumulation of mercury levels in maternal and fetal organs in pregnant Fischer 344 rats, based on the theory and information that neutral amino acids have protective effects against mercury poisoning and garlic contains a large of neutral amino acids. The results obtained are as follows: 1. On the 20th day of gestation, the maternal body weight in 20 mg/wt$\cdot$kg methyl mercuric chloride groups was 76.1% of those in control group, but those recovered to be 81.2% and 93.6% by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 2. The mercury levels in maternal organs were reduced 6.2% and 47.2% (p<0.05) in kidney, 8.2% and 42.1% (p<0.05) in spleen, 9.7% and 40.9% (p<0.05) in blood, 35.6% (p<0.05) and 67.2% (p<0.05) in liver, 38.0% (p<0.05) and 57.6% (p<0.05) in brain, by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 3. The mercury levels were reduced 22.4% and 44.3% (p<0.05) in placenta, and 34.7% (p<0.05) and 54.9% (p<0.05) in fetal body, by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 4. The mercury levels in fetal organs were reduced 17.5% and 46.7% (p<0.05) in kidney, 15.1% and 37.0% (p<0.05) in brain, 30.2% (p<0.05) and 46.7% (p<0.05) in liver, by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 5. Mercury levels in maternal kidney were 6.73~7.71 times higher than those in fetal kidney, but those in fetal liver and brain were 1.67~2.25 times and 1.98~2.93 times higher than those in maternal liver and brain, respectively. In conclusion, Korean garlic decrease the accumulation of mercury levels in maternal and fetal organs in pregnant Fischer 344 rats as increasing the dose.

• Journal of Microbiology and Biotechnology
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• v.25 no.9
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• pp.1532-1536
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• 2015

To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 (1 × 10¹¹ CFU/g of each strain), and investigated its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 × 10¹⁰ CFU/rat/day), which was administered orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent increases of blood triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p < 0.05). KF treatment slightly, but not significantly, shortened the escape latency daily for 4 days. Oral administration of KF restored age-suppressed doublecortin and brain-derived neurotrophic factor expression in aged rats. Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.337-344
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• 1998

The objective of the present study was to investigate the effect of senescence on the binding properties of muscarinic receptors in the neostriatum of young (3 months), middle-aged (18 months) and aged (33 months) male Fischer 344 x Brown Norway hybrid rats by employing direct binding of selective radiolabeled antagonists. Using the selective M, muscarinic receptor antagonist, $[^3H]$AF-DX384, as the ligand, no significant difference in the maximal receptor density (Bmax) was observed in the neostriatum among any age-groups. In contrast, with the selective M, receptor antagonist, $[^3H]$4-DAMP, a significant increase in the number of muscarinic receptors was observed in neostriatal membrane fractions prepared from the aged animals relative to that observed in the young rats. For each ligand there was no age-related change in its affinity (Kd) for the muscarinic receptors. These results indicate that the observed age-related changes in the muscarinic receptor density may not be necessarily decremuntal and depend upon the muscarinic receptor subtype examined.

• Journal of Nutrition and Health
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• v.27 no.9
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• pp.949-956
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• 1994

The effect of zinc deficiency on certain immunological parameters was investigated using intragastric tube feeding to obviate decreased food intake and altered eating pattern. Male, Fischer 344 rats were bilaterally adrenalectomized(ADX) or sham operated(SHAM). ADX rats received 0.9% NaCl in their drinking water and corticosterone injections at the dose of 1mg/kg of body weight three times per day. After recovery, one half of ADX and SHAM animals were tube-fed a purified, liquid diet containing either two ppm of zinc(zinc-deficient, force-fed ; ZDF) or 50ppm(zinc-replete, force-fed ; ZRF) for 19 days. They received identical amounts of diet based on the intake of ad libitum-fed, zinc-replete rats. Although they received identical amounts of food, ZDF rats grew at a slower rate compared to ZRF rats in both SHAM and ADX rats. Regardless of surgery, force-feeding rats the zinc-deficient diet resulted in a substantial decrease in serum zinc levels. The weights of the thymus, lymph node, and spleen were lower in SHAM-ZRF rats compared to SHAM-ARF rats. Marginal zinc deficiency caused lymphopenia in SHAM animals. However, these differences in lymphoid tissues and cells between SHAM-ZDF and SHAM-ZRF rats disappeared in ADX rats. These results indicate that the impaired growth of lymphoid tissues observed in zinc-deficient, sham-operated animals can be attributed to elevated serum corticosterone levels under the conditions of our experiments.