• Preventive Nutrition and Food Science
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• v.5 no.4
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• pp.230-233
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• 2000

The present work was designed to determine whether change in fluidity of the mitochondrial membrane affects mitochondrial {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase characteristics in NIDDM-prone BHE/Cdb rat. Isolated mitochondria fom BHE/Cdb rat fed a 6% coconut oil or corn oil were functionally tested by an analysis of its respiration and the coupling of this process to ATP synthesis in presence of oligomycin, a specific inhibitor of oxidative phosphorylation (OXPHOS), that binds to the {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase. Mitochondria from rats fed coconut oil were more responsive to the inhibitory action of oligomycin with respect to state 3 respiration, respiratory control (RC) ratio and ADP:P (P/O) ratio than were mitochondria from rats fed corn oil. In state 3 respiration, mitochondria from rats fed coconut oil consumed less oxygen than did mitochondria from rats fed corn oil. RC ratio was lower in the mitochondria from rats fed coconut oil than was mitochondria from rats fed corn oil. In P/O ratio, the mitochondria from rats fed coconut oil had a lower P/O ratio than did mitochondria from rats fed corn oil. The data showed that the chang influidity of the mitochondrial membrane by dietary fat affected mitochondrial {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase characteristics. The present study on diet differences in {TEX}$F_{1}${/TEX}{TEX}$F_{0}${/TEX}ATPase characteristics provides considerable insight into the role diets play in the control of mitochondrial function, expecially OXPHOS in NIDDM with mitochondrial defects.

• Journal of Nutrition and Health
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• v.30 no.4
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• pp.379-385
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• 1997

This study was designed to determine whether genetic defects in the efficiency of ATP synthesis existed in the NIDDM-prone BHE/cdb rat and to determine whether these defects caused the development of glucose intolerance. Thyroxine treatment provided an excellent clue as to the nature of the genetic defects in this rat. The characteristics of hyperhyroid and control Sprague-Dawley(SD) and BHE/cdb rats were studied. Hyperthyroidism was induced through the addition of thyroxine($T_4$) to the diet(2mg/kg of diet). Active proton conductances and passive proton conductances were tested. Mitochondria from hyperhyroid BHE/cdb rats were less efficient iii active proton conductances than mitochondria from hyperhyroid SD rats. It showed that decreased efficiency of ATP synthesis in the BHE/cdb rat was probably related to defects in active proton conductance, Indicating aberrant FoATPase. The levels of $F_1F_0$ATPaseATPase activity were tested. Mitochondria from hyperthyroid BHE/cdb rats were less active than mitochondria from hyperthyroid SD rats. This may be an attribute of aberrant F$_1$ATPase and may contribute to the BHE/cdb strain s characteristic of reduced ATP synthesis efficiency. Glucose tolerances were tested. BHE/cdb rats were profoundly affected by thyroxine, whereas SD rats were less so. It showed that the diabetes phenotype in BHE/cdb rats was related to defects in thyroxine-induced uncoupling. These results showed the decreased efficiency of ATP synthesis due to genetic defects in $F_1F_0$ATPase had relevance to the characteristic of impaired glucose tolerance in the NIDDM-prone BHE/cdb rat.

• Toxicological Research
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• v.11 no.1
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• pp.91-101
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• 1995

A perinatal and postnatal study of KTC-1, a new semisyntheitic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 12, 27.6, and 63.5 mg/kg/day were administered to dams orally by gavage from day 17 of gestation to day 21 of lactation. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. At 63.5 mg/kg/day, weakness, dark-red discharge around eyes, a loss in body weight, and a decrease in food and water consumption were observed in dams. An increase in the weight of adrenal gland and spleen, and a decrease in the weight of kidney and heart were also found. An increase in neonatal deaths during the lactation period, a loss in body weight, a delay in physical development, a decrease in traction ability, an increase in the number of errors and the time required for the multiple T-maze trial were found in F1 offspring. In addition, an increase in the incidence of visceral variations and retarded ossification were observed in F1 4 day old rats. An increase in the incience of skeletal anomalies was seen in F2 fetuses. There were no sings of maternal toxicity or embryotoxicity at 12 and 27.6 mg/kg/day. From the results mentioned above, it can be concluded that the no-effect dose levels(NOELs)for dams, F1 offspring, and F2 fetuses are 27.6 mg/kg/day.

• Development and Reproduction
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• v.26 no.4
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• pp.175-182
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• 2022

Previous studies, including our own, indicate that distinct morphological changes in rodent adrenal cortex could be induced by exposure of endocrine disrupting chemicals (EDC). In the present study, we conducted histological analyses of adrenocortical substructure using a nonylphenol-treated F1 rat model. The adrenal weight of NP-5000 group was significantly declined in female rats (p<0.001), while the adrenal weights of NP-treated groups were not significantly changed in male rats. The thickness of zona glomerulosa layers of female rats in NP-5000 group was significantly declined (p<0.001) but zona fasciculata layers were not changed. The zona reticularis layers of NP-treated group were significantly thinner than those of control group (NP-50, p<0.05; NP-5000, p<0.01). In male adrenal glands, there was no significant change of zona glomerulosa layers in NP-treated groups while the thickness of zona fasciculata in NP-5000 group was significantly decreased (p<0.01). Like female rats, the thickness of zona reticularis in NP-treated groups was significantly decreased (NP-50, p<0.001; NP-5000, p<0.05). Present study demonstrated that the adrenal histology could be altered by low-dose NP exposure in F1 rats, and the effect might be sexually dimorphic. Further study will be helpful for understanding possible adrenal pathophysiology induced by EDC exposure, and EDC-related sexually dimorphic phenomena in rodent adrenals.

• 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.

• Journal of Pharmaceutical Investigation
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• v.15 no.2
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• pp.73-82
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• 1985

Each parching Anemarrhenae Rhizoma with 25% ethanol and normal saline has been used for anti-inflammatory, expectorant, antipyretic, sedative and diuretic, and so on. In order to investigate the differences of referential efficacy about each fractionated part of the aqueous extracts, pharmacological studies were carried out. The results of studies were summerized as follows : 1. By the administration of 25% ethanol treated preparation (F-I-1), the increase in urinary volume and $Na^+$ extraction was significantly recognized. 2. The excretion of electrolyte $Na^+$ by saline solution treated preparation (F-II-1) was significantly recognised in normal rats. 3. The increase of urinary volume and urinary $Na^+$ and $Cl^-$ excretion by F-I-1 and n-butanol insoluble parts of F-I-1 (F-I-3) was significantly recognized in $HgCl_2-induced$ acute renal failure of rats. 4. The increase of plasma $Na^+$ by F-I-1 and urea nitrogen by F-I-1 and F-I-3 in acute renal failure of rats was significantly recognized. 5. The increase of urinary volume by F-I-1 and F-I-3 was recognised in mice.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2002.11a
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• pp.12-20
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• 2002

1. 질병명 : Interstitial pneumonia 2. 본질명의 개요 역사 및 역학 Michael R Elwell, Joel F Mahler, G N Rao: “ Have You Seen This\ulcorner" ; Inflammatory Lesions in the Lungs of Rats. Toxicologic Pathology, 25: 529-531, 1997. Male and female F344 rats, approximately 19 weeks old, from prechronic toxicity studies performed for NTP/NIEHS over a period of several years at different laboraories located throughout the US. The rats were supplied by 2 different production colonies located in the eastern and western areas of the US. Gross findings ㆍ In some rats the lesions were noted as pale or tan foci in the lungs Microscopic findings ㆍ A prominent increase in perivascular lymphocytes ㆍ A variable increase in the amount of peribronchiolar lymphoid tissues ㆍ Frequently an inflammatory cell exudate within the alveolar spaces ㆍ Focal hyperplasia of alveolar type 2 cells Similar lung lesions were not observed in B6C3F1 mice concurrently on study with affected rats. Similar lung lesions were not observed in F344 rats at the end of 2-year NTP studies. Virus, mycoplasma, bacterial serology, bacterial culture, protozoal identification: negative EM: ㆍ No virus particles were identified. ㆍ Rod shaped bacteria were observed in the alveolar spaces. ㆍ Bacteria were not observed in the bronchi/ bronchioles of rats with alveolar organism. (omitted)

• Toxicological Research
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• v.13 no.4
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• pp.331-338
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• 1997

A teratogenic study on Original Woo-Whang-Chung-Sim-Won was carried out in SpragueDawley rats. Original Woo-Whang-Chung-Sim-Won suspended in distilled water was administered to pregnant dams by oral gavage during organogenesis period (from 7th to 17th day of gestation) at daily doses of 1/9, 1/3 and I pill/kg. About two-thirds of dams were sacrificed at 20th day of gestation to scrutinize the pregnant performances and fetal development, and the remaining dams were allowed to deliver. The growth, reflex, behaviour and reproductive function of F1 offsprings were examined. There was no treatment-related difference in body weight, food consumption and necropy findings of dams. No gross, skeletal and visceral abnormalities was observed in F1 fetuses from dams treated with Original Woo-Whang-Chung-Sim-Won. F1 offsprings did not show any treatment-related difference in growth, reflex, behaviour and reproductive peuformance. At caesarean section of F1 dams, no growth retardation and gross abnormality was observed in F2 fetuses. In conclusion, Original Woo-Whang-Chung-Sim-Won did not show any potential teratogenic activity in rats.

• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.16-22
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• 2003

BBP (Butyl benzyl phthalate), a widely used plasticizer. can enter the food and environment as consequence of its manufacture, use, and disposal. BBP was found to be developmental and teratogenic or endocrine disrupting chemical in rats. The effects of BBP were investigated in female rats (P) and second generation (F1) via lactations. Sprague-Dawley were given BBP by oral administration at 0, 5, 10, 100, 1000 mg/kg on day 0 to 21 of lactation period. The results were as follows : At maternal findings, there were some significant changes (p<0.05) in relative organ weight, especially liver and uterus weight by BBP administration. In estrous cycle, high treated group was inclined to be proestrus or estrus compared to control group. BBP indues estrous cycle earlier than the control group. At fetal findings, there were some significant changes in relative liver and spleen weight, especially 100, 1000 mg/kg administered groups. The relative weight of ventral prostate was decreased, so it was represent to dose-response tendency. Parent rats (P) were detected monobenzyl phthalate (MBeP) 3.21~5.81 $\mu\textrm{g}$/ml in 100, 1000 mg/kg dose groups. MBeP of male and female fetuses (F1) were detected at the level of 1.21~2.63 $\mu\textrm{g}$/ml of serum. Male serum concentration oi MBeP was higher than the females'. Estrogen receptor $\alpha$ expression by BBP and bisphenol A in uterus and testis of F1 were studied. The ER$\alpha$ expression were increased in F1 male testis and female uterus. F1 male showed distint ER$\alpha$ expression, especially in the combined exposrue. Synergistic ER$\alpha$ expression was found by combined treatment group of BBP and bisphenol A. From the above results, it could be concluded that the effects of dams and F1 by BBP administration during lactation period were estrogenic, and BBP can transfer to F1 via lactation, and make estrogenic at F1 reproductive organs.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.125-132
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• 2002

To evaluate the modifying effect of Kwao Kreu, Pueraria mirifica (PM) well-known as a rejuvenating folk medicine from Thailand, peri- and post-natal studies were carried out in rats. PM extract was administered to pregnant Sprague Dawley (SD) rats by oral gavage from gestation 6 (GD 6) to postnatal day 21 (PND 21). The amount of administered in this study was 0.042, 0.42 and 4.2 mg/kg/day, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. Treatment related changes in body weight, food consumption and lactation of dams were not observed. F1 fetuses in external abnormality, physical development, reflex/sensory functions and behavioral development were not found. No adults and F1 fetuses in organ weight was found with the exception of vagina and uterus of F1 fetuses. The results showed that PM extract, up to 4.2 mg, had no adverse effects on the peri- and post-natal development of rats. Therefore, PM extract has no adverse effects on peri- and post-natal development of rats.