• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.327-332
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• 2011

It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and diabetic opium-addicted brain and liver cells were significantly higher than the both normal and diabetic rats. In addition, we found that apoptosis in brain cells of opium-addicted and diabetic opium-addicted male rats were significantly higher than opium-addicted and diabetic opium-addicted female, whereas apoptosis in liver cells of opium-addicted and diabetic opium-addicted female rats were significantly higher than opium-addicted and diabetic opium-addicted male. Overall, these results indicate that opium probably plays an important role in brain and liver cells apoptosis, therefore, leading neurotoxicity and hepatotoxicity. These findings also in away possibly means that male brain cells are more susceptible than female and interestingly liver of females are more sensitive than males in induction of apoptosis by opium.

• Toxicological Research
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• v.24 no.2
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• pp.137-150
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• 2008

Sexually mature male and female rats were orally intubated with the organophosphorus insecticide, Pestban at a daily dosage of 7.45 or 3.72 mg/kg bwt, equivalent to 1/20 and 1/40 $LD_{50}$, respectively. Male rats were exposed for 70 days, while the female rats were exposed for 14 days, premating, during mating and throughout the whole length of gestation and lactation periods till weaning. The results showed depressed acetylcholinesterase(AChE) activity in the brain of parents, fetuses and their placentae in a dose-dependent manner. The fertility was significantly reduced with increasing the dose in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre-and postimplantation losses were significantly increased. The incidence of resorptions was more pronounced in treated female compared to male group and was dose dependant. The behavioral responses as well as fetal survival and viability indices were altered in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group and occurred in a dose-related manner. The recorded morphological, visceral, and skeletal anomalies were significantly increased with increasing the dose in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to Pestban would cause adverse effects on fertility and reproduction.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.268-275
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• 2022

Objectives: This toxicological study was performed to assess for potential toxicity and to determine the approximate lethal dose of SU-Eohyeol pharmacopuncture (SUEP) following a single intramuscular injection of SUEP into male and female Sprague-Dawley (SD) rats. Methods: The groups in our experiment consisted of an experimental group treated with SUEP at a dose of 1.0 mL/animal and a control group injected with a normal saline solution, and five male and female rats were placed in each group. Each animal was administered a single intramuscular injection. We monitored all rats for clinical signs and body weight changes for 14 days after administration. At the end of the observation period, the rats were euthanized and autopsied, and localized tolerance examinations were conducted at the site of administration of the test substance. Results: There were no deaths in either sex in the SUEP-treated group. There was no significant difference between the SUEP-treated group and the control group in the clinical signs and weight changes among the rats. In addition, no significant SUEP-related changes were observed on autopsy findings or local tolerance examinations at the injection site by histopathological examination. Conclusion: Our results suggest that the approximate lethal dose of a single intramuscular administration of SUEP in female and male rats under the conditions of this study is greater than 1.0 mL/animal. To determine the safety of the use of SUEP in Korean medical clinical practice, additional toxicity studies will be needed.

• 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.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.325-331
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• 2009

The object of this study was to evaluate the single oral dose toxicity of Low Molecular Weight Fucoidan (LMF) in male and female rats. LMF was administered to female and male SD rats as an oral dose of 2,000, 1,000 and 500 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation organ weight and histopathology of 14 principle organs were examined upon necropsy. As the results, no LMF treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2,000 mg/kg in both female and male rats except for some sporadic findings not LMF treatment related toxicological signs. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of LMF after single oral treatment in female and male rats were considered over 2,000 mg/kg - the limited dosages recommended by KFDA Guidelines [2005-60, 2005], respectively.

• Journal of Nutrition and Health
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• v.36 no.4
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• pp.359-367
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• 2003

The purpose of this study was to examine the impact of soy protein and soy isoflavones on bone and mineral density in young female Sprague-Dawley rats. Fifty eight rats (body Weight 75 $\pm$ 5 g) were randomly assigned to one of four groups, consuming casein, soy protein concentrate, soy protein isolate (57 mg isoflavones/100 g diet) or casein added isoflavones (57 mg isoflavones /100 g diet). All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur on 3, 6, 9 weeks after feeding. The serum and urine concentrations of Ca and P were determined. Diet did not affect weight gain and mean food intake. Food efficiency ratio was lower In soy protein groups. The serum concentration of Ca and P were not changed by soy protein and isoflavones. Urinary Ca and P excretion were not significantly different. Spine BMD was significantly increased by soy protein isolate on 3 and 6 weeks after feeding. Femur BMD was significantly increased in the groups of soy protein isolate and isoflavones adding on after 9 weeks. Therefore, soy protein with rich isoflavones may be beneficial on spine and femur BMD increasement in growing female rats.

• Toxicological Research
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• v.16 no.1
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• pp.27-31
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• 2000

Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. EPA and OECD are developing screening programs using validated test systems to determine whether certain substances may have an effect on humans. In the present study, the establishment of in vivo short-term test system for pubertal female assay with thyroid to detect endocrine disrupting chemicals was tried using a model substance, methoxychlor (MC), a chlorinated hydrocarbon insencticide. Forty female rats were assigned to four groups. MC was administered at dose levels of 0, 8, 40 and 200mg/kg by gavage to female rats from day 21 post partum to the completion of vaginal opening. We evaluated body weight change, age at vaginal opening, onset of estrous cyclicity, age at first esturs, ovary weight, and serum concentrations of thyroxine and thyroid stimulating hormone in female rats. The age at vaginal opening of females receiving 40 200mg/kg was significantly younger than control. The onset of estrus cyclicity and age at first estrus of females receiving 200mg/kg was also younger than controls. There was no effect of treatment on body weight, ovary weight, and hormone concentration. Based on these results, it can be concluded that application of MC at dose level of 40mg/kg affects the vaginal opening and application of MC at dose level of 200mg/kg accelerates the vaginal opening and the onset of estrus cylicity.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.12-22
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• 1997

Intravenous and oral acute toxicity tests in ICR mice and SD rats and percutaneous acute toxicity tests in SD rats and NZW rabbits were conducted to evaluate the toxicity of DA-5018 and DA-5018 cream, respectively Clinical signs observed in mice and rats after the administration of DA-5018 were similar regardless of administration route. The observed clinical signs were jumping, wild running, lacrimation, ataxia, reddening of extremities and ears, ventral or lateral recumbency, respiratory distress, cyanosis, convulsion and death. Pulmonary enlargement and hemorrhage were observed in the animals died immediately after the dosing of DA-5018. At terminal necropsy, pulmonary enlargement and hemorrhage, corneal opacity and focal scabbing and depilation around nose were seen. LD$_{50}$ Values of DA-5018 are 11.5 mg/kg (mice, male), 12.6 mg/kg (mice, female), 88.3 mg/kg (rat, male) and 73.2 mg/kg (rat, female) in oral toxicity tests and 11.0 mg/kg (mice, male), 18.7 mg/kg (mice, female), 0.12 mg/kg (rat, male) and 0.32 mg/kg (rat, female) in i.v. toxicity tests. In the percutaneous acute toxicity tests of DA-5018 cream, no deaths occured in all the tested groups during 14-day observation period. There were also no abnormalities in the general conditions, body weight changes and on necropsy findings in all groups. LD$_{50}$ values of 0.1 ~0.9% DA-5018 creams in male and female rats and rabbits are >2000 mg/kg./kg.

• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.18-26
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• 2014

Objectives: This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV) in Sprague-Dawley (SD) rats. Methods: Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: (1) Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2) The rats in the high-dose group showed no significant changes in weight compared to the control group. (3) No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs), and biochemistry were observed among the recovery groups. (4) No changes in organ weights were observed during the recovery period. (5) Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion: The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

• Journal of the Korean Society of Food Science and Nutrition
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• v.12 no.3
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• pp.273-283
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• 1983

In order to investigate the effect of the combined dietary animal and vegetable proteins on growing female and male rats and mice. 25 female and 25 male rats of 4 weeks old weighing approximately 43-65g and 47-60g, respectively, were subjected to feeding trials for 4 weeks and then subsequently to metabolic trials for 10 days. In case of mice, 25 female and 25 male mice of 4 weeks old weighing approximately 12-17g and 12-16g, respectively, were equally treated. The dietary energy level was set as 3600 kcal ME/kg, and protein and fat provided respectively 12 and 5% of the dietary energy. The rest 83% of the energy level was supplied with appropriate amounts of starch and glucose. The following results were obtained. The body weight gain of female and male rats were increased as the combined dietary animal protein level increased. Whereas that of male mice was the highest for the diet E(Ap 10+Vp 90). Food efficiencies both of female and male rats were improved as combined dietary of animal protein increased. Male rats were superior to that of female. In the mice, the food efficiency value of male mice was superior to that of female. And the values of the male showed the same fashion as that in the growth rate, although it was not for the female. Protein efficiencies, both of female and male rats, were improved as combined dietary of animal protein level increased. That of male mice was in accord with the body weight gain and food efficiencies. But that of female mice was not accordant. Nitrogen retention of the experimental diets in the same protein level was in proportion to nitrogen intake. That of male mice was improved as animal protein level increased, but, that of female mice was not. Body protein utilizability was found to be superior in mice to rats. Blood serum protein level was not found to be affected by the experimental diets in the same protein level. The best combination ratio of animal and vegetable protein seems to be variable depending on the sex and species of animals, and the best diets for female and male rats and female and male mice were found to be experimental diet A(Ap 10+Vp 90) or diet B(Ap 75+Vp 25), diet C(Ap 50+Vp 50), and diet E(Ap 10+Vp 90), respectively. From the above-mentioned results that there was no difference in growth rate of body weight gain from the weanling period to puberty, and that the protein requirements of rats and mice were different from each other.