• Archives of Pharmacal Research
• /
• 제26권11호
• /
• pp.943-950
• /
• 2003

In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice. The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights of the spleen and thymus weights and decreased the number of splenic cells. In addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs. Meanwhile, only the antibody response was significantly suppressed by treatment with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1 ,2-DBP on the hepatotoxic parameters were compared in female BALB/c mice. When mice were treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the activities of serum alanine aminotransferase and aspartate aminotransferase elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200 also contributes to the immnunotoxicity, although 2-BP is a major component.

• 동의생리병리학회지
• /
• 제25권1호
• /
• pp.100-108
• /
• 2011

The object of this study was two. One was if Polygonati Rhizoma preparata had a benzo(a)pyrene, the other was to evaluate the single dose toxicity of 9 repetitive steaming and fermenting processed Polygonati Rhizoma, dried root parts of Polygonati Rhozoma preparata extract, in male and female mice. We measured a content of benzo(a)pyrene in Polygonati Rhozoma preparata using a method with HPLC/FLD. And for single dose toxicity, aqueous extracts of Polygonati Rhozoma preparata (EPP; Yield = 35.4 %) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for slight soft feces sporadically detected in EPP treated male mice at 1 day after administration. In addition, no EPP-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that benzo(a)pyrene was not existed in Polygonati Rhozoma preparata and the 50% lethal dose and approximate lethal dose of EPP aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines. However, it also observed that the possibilities of digestive disorders, like soft feces when administered over 500 mg/kg of EPP aqueous extracts in the present study.

• Toxicological Research
• /
• 제23권4호
• /
• pp.373-382
• /
• 2007

This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body wt.). The mortality and changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after dosing with PGB-1. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that PGB-1 may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-1 were considered over 2000 mg/kg in both female and male mice.

• 한국발생생물학회지:발생과생식
• /
• 제17권1호
• /
• pp.17-24
• /
• 2013

This study examined the expression of inhibitor of DNA-binding (Id) proteins and vascular endothelial growth factor (VEGF) in the ovary according to female age using a mice model as the first step in investigating the potential role of Ids and VEGF in ovarian aging. C57BL inbred female mice of three age groups (6-9, 14-16, and 23-26 weeks) were injected with 5 IU pregnant mare's serum gonadotropin (PMSG) in order to synchronize the estrus cycle. After 48 h, ovarian expression of Ids and VEGF was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. Ovarian apoptosis was examined by ovarian expression of Bcl-2 and Bcl-xL. Expression of Id-1 and VEGF was decreased with advancing female age, but not Id-2, Id-3, and Id-4. In particular, their expressions were significantly decreased in aged mice of 23-26 weeks compared with the young mice of 6-9 weeks (p < 0.05). In contrast, ovarian apoptosis was greatly increased in the aged mice compared to the young mice. This result suggests that Id-1 may have an implicated role in ovarian aging by associating with VEGF.

• Molecules and Cells
• /
• 제38권12호
• /
• pp.1079-1085
• /
• 2015

Originally, activins were identified as stimulators of FSH release in reproduction. Other activities, including secondary axis formation in development, have since been revealed. Here, we investigated the influence of activin ${\beta}_A$ on the body, including the gastro-intestinal (GI) tract. Initially, the activin ${\beta}_A$ protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin ${\beta}_A$ in muscle was higher in female than male mice. Subsequent results revealed that stomach and intestine were severely damaged in pCMV-rAct-injected mice. At the cellular level, loss of parietal cells was observed, resulting in increased pH within the stomach. This phenomenon was more severe in male than female mice. Consistent with damage of the stomach and intestine, activin ${\beta}_A$ often led to necrosis in the tip of the tail or foot, and loss of body weight was observed in pCMV-rAct-injected male but not female mice. Finally, in pCMV-rAct-injected mice, circulating activin ${\beta}_A$ led to death at supraphysiological doses, and this was dependent on the strain of mice used. Taken together, these results indicate that activin ${\beta}_A$ has an important role outside of reproduction and development, specifically in digestion. These data also indicate that activin ${\beta}_A$ must be controlled within a narrow range because of latent lethal activity. In addition, our approach can be used effectively for functional analysis of secreted proteins.

• Journal of Microbiology and Biotechnology
• /
• 제27권12호
• /
• pp.2094-2103
• /
• 2017

Aging is associated with distinct changes in immune cells and a decline in immune function, leading to increased susceptibility to infection and reduced responses to vaccination. Certain strains of lactic acid bacteria exert beneficial effects on the immune system. Previously, we reported that Weissella cibaria JW15 isolated from kimchi possesses immune stimulatory activity in vitro. In the present study, we further investigated whether oral administration of JW15 improves immune function in aged mice. Eighteen-month-old female mice were administered JW15 daily at low (JW15-L; $1{\times}10^8CFU/mouse$) or high dosage (JW15-H; $1{\times}10^9CFU/mouse$), or with Lactobacillus rhamnosus GG (LGG) using oral gavage. Two-month-old female mice were included as healthy young mice. After 4 weeks, the mice were euthanized and immune profiles were analyzed using whole blood and spleen. In complete blood count analysis, the numbers of white and red blood cells were significantly increased in the JW15-L group compared with those in the old mouse (OM) control group. In addition, administration of either JW15 of LGG resulted in higher numbers of splenocytes in comparison with the OM group. Furthermore, proliferative potentials were higher in all probiotic groups than OM. Cytokines such as IFN-${\gamma}$ and IL-6 were secreted at higher levels in splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA expression of various cytokines was altered in the JW15 groups. Collectively, these results suggest that JW15 supplementation induces immunomodulatory effects in aged mice and indicate JW15 as a potential probiotic strain to improve immune function in aged animals.

• Biomolecules & Therapeutics
• /
• 제8권1호
• /
• pp.84-92
• /
• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

• 한국발생생물학회지:발생과생식
• /
• 제6권1호
• /
• pp.31-35
• /
• 2002

생쥐에서 페르몬으로 알려진 소수성의 분자와 결합하는 major urinary proteins(MUPs)는 부분적으로 성장 호르몬(GH)의 조절을 받는다. 본 연구에서는 MT-GRF로 형질전환되어 성장호르몬이 증가된 생쥐에서 MUP의 발현을 조사하였다. 이 MT-GRF로 형질전환된 생쥐의 소변에서 MUP이 대조군보다 심하게 저하되어 나타났고, 암컷보다 수컷에서 더 저하되어 나타났다. 또한 MT-GRF를 근육에 주사한 생쥐에서도 MUP는 저하되어 나타났다. 부가하여, MT-GRF로 형질전환시킨 생쥐의 소변에서 전기영동상에서 albumin과 동일하게 이동하는 고분자의 단백질이 다량으로 관찰되었는데 신장의 사구체 여과가 손상되었음을 암시하고 있다. 이 혈장 단백질의 손실도 암컷보다 수컷에서 심하게 나타났다. 결과적으로 GRF의 과다생성은 성별에 차별화된 영향을 미치면서 GH로 형질전환된 동물모델에서 관찰되는 MUP의 발현과 사구체 기능의 변화를 동일하게 유발하고 있었다.

• Clinical and Experimental Reproductive Medicine
• /
• 제50권3호
• /
• pp.170-176
• /
• 2023

Objective: Autophagy is highly active in ovariectomized mice experiencing hormone deprivation, especially in the uterine mesenchyme. Autophagy is responsible for the turnover of vasoactive factors in the uterus, which was demonstrated in anti-Müllerian hormone receptor type 2 receptor (Amhr2)-Cre-driven autophagy-related gene 7 (Atg7) knockout (Amhr-Cre/Atg7^f/f mice). In that study, we uncovered a striking difference in the amount of sequestosome 1 (SQSTM1) accumulation between virgin mice and breeder mice with the same genotype. Herein, we aimed to determine whether repeated breeding changed the composition of mesenchymal cell populations in the uterine stroma. Methods: All female mice used in this study were of the same genotype. Atg7 was deleted by Amhr2 promoter-driven Cre recombinase in the uterine stroma and myometrium, except for a triangular stromal region on the mesometrial side. Amhr-Cre/Atg7^f/f female mice were divided into two groups: virgin mice with no mating history and aged between 11 and 12 months, and breeder mice with at least 6-month breeding cycles with multiple pregnancies and aged around 12 months. The uteri were used for Western blotting and immunofluorescence staining. Results: SQSTM1 accumulation, representing Atg7 deletion and halted autophagy, was much higher in virgin mice than in breeders. Breeders showed reduced accumulation of several vasoconstrictive factors, which are potential autophagy targets, in the uterus, suggesting that the uterine stroma was repopulated with autophagy-intact cells during repeated pregnancies. Conclusion: Multiple pregnancies seem to have improved the uterine environment by replacing autophagy-deficient cells with autophagy-intact cells, providing evidence of cell mixing.

• Animal Bioscience
• /
• 제36권1호
• /
• pp.43-52
• /
• 2023

Objective: This study aimed to examine the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy in cytokeratin-18 (K18)-hACE2 transgenic mice. Methods: To determine the expression of hACE2 mRNA in the female reproductive tract of K18-hACE2 mice, real-time polymerase chain reaction (RT-PCR) was performed using the ovary, oviduct, uterus, umbilical cord, and placenta. SARS-CoV-2 was inoculated intranasally (30 μL/mouse, 1×10⁴ TCID₅₀/mL) to plug-checked K18-hACE2 homozygous female mice at the pre-and post-implantation stages at 2.5 days post-coitum (dpc) and 15.5 dpc, respectively. The number of implantation sites was checked at 7.5 dpc, and the number of normally born pups was investigated at 20.5 dpc. Pregnancy outcomes, including implantation and childbirth, were confirmed by comparison with the non-infected group. Tissues of infected mice were collected at 7.5 dpc and 19.5 dpc to confirm the SARS-CoV-2 infection. The infection was identified by performing RT-PCR on the infected tissues and comparing them to the non-infected tissues. Results: hACE2 mRNA expression was confirmed in the female reproductive tract of the K18-hACE2 mice. Compared to the non-infected group, no significant difference in the number of implantation sites or normally born pups was found in the infected group. SARS-CoV-2 infection was detected in the lungs but not in the female reproductive system of infected K18-hACE2 mice. Conclusion: In K18-hACE2 mice, intranasal infection with SARS-CoV-2 did not induce implantation failure, preterm labor, or miscarriage. Although the viral infection was not detected in the uterus, placenta, or fetus, the infection of the lungs could induce problems in the reproductive system. However, lung infections were not related to pregnancy outcomes.