• Radiation Oncology Journal
• /
• 제21권4호
• /
• pp.315-321
• /
• 2003

목적: 발육 중인 백서 태아 대뇌 피질에서 방사선조사에 의한 아포토시스 반응에 대하여 알아보고자 하였다 대상 및 방법: 임신 백서의 태령 17 내지 19일(E17$\~$E19)에 선형가속기의 X-ray를 이용하여 어미 쥐의 복부에 방사선을 조사하였다. 방사선량에 따른 아포토시스를 보기 위하여 1, 2, 3, 4 Gy를 전후 조사면으로 방사선조사를 시행하고 5시간 후 백서 태아의 뇌를 획득하였다. 시간 경과에 따른 아포토시스를 보기 위하여 E7$\~$E19에 2 Gy의 방사선을 조사한 후 1, 3, 6, 12, 24시간에 각각 백서 태아의 뇌를 획득하였다. 대조군은 방사선을 조사하지 않은 임신 쥐를 같은 조건하에서 사육하여 각 군당 3마리씩 할당하였다. 아포토시스 세포는 면역조직화학적 방법(TUNEL, In situ 707-mediated dUTP nick end labeling)으로 염색하여 관찰하였다 결과: 백서 태아 대뇌 피질에서 TUNEL 양성인 세포는 광학현미경하에서 전형적인 아포토시스의 형태학적 특징을 나타내었다 대조군에서는 대뇌 피질의 전 층에서 TUNEL 양성세포를 거의 발견할 수 없었다. 1 Gy의 방사선 조사 후 5시간에 대뇌피질 전 층에서 미약하게 관찰되었으나 2 Gy에는 전 층에서 1 Gy 경우보다 더 증가하였고 그중 뇌실대와 중간대에서 피질대보다 더 많이 나타났다. 조사된 1$\~$4 Gy 범위에서 방사선량이 증가할수록 TUNEL양성세포가 더욱 증가하는 것을 볼 수 있었다. 2 Gy의 방사선 조사 후 3시간부터 TUNEL양성세포가 관찰 되기 시작하여 방사선 조사 후 6시간에 최고점을 이루었으며 이는 24시간까지 지속되었다. 결론: 발육 중인 백서 태아 대뇌피질에서 방사선에 의한 아포토시스의 전형적인 형태학적 특징을 관찰할 수 있었다. 아포토시스는 뇌실대와 중간대에서 피질대보다 더 많이 나타났으며 이는 줄기세포와 초기의 분화세포에서 방사선조사에 대한 감수성이 더욱 민감함을 시사하였다.

• Journal of Ginseng Research
• /
• 제43권2호
• /
• pp.242-251
• /
• 2019

Background: Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. Methods: This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague-Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague-Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. Results and conclusion: No test item-related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.

• 대한수의학회지
• /
• 제44권4호
• /
• pp.523-532
• /
• 2004

The present study was carried out to investigate the potential adverse effects of amitraz on pregnant dams after maternal exposure during the gestational days (GD) 1 through 19 in Sprague-Dawley rats. The test chemical was administered orally to pregnant rats at dose levels of 0, 3, 10, or 30 mg/kg/ day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings on GD 20 were examined. In the 30 mg/kg group, an increase in the incidence of abnormal clinical signs and death, a suppression in the body weight gain, and a decrease in the food consumption were observed. A decrease in the liver weight and increases in the kidneys, adrenal glands and heart weights were also found. Serum biochemical investigations revealed increases in the aspartate aminotransferase (AST), total bilirubin, and chloride. In addition, an increase in the fetal death and decreases in the litter size and fetal body weight were seen at caesarean section. Inthe 10 mg/kg group, an increase in the incidence of abnormal clinical signs, decreases in the food consumption and liver weight, increases in the total bilirubin and chloride, and a decrease in the fetal body weight were observed. There were no adverse effects on clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings in the 3 mg/kg group. Based on the results, it was concluded that the 19-day repeated oral dose of amitraz to pregnant rats caused increases in the clinical signs, kidneys, adrenal glands and heart weights, AST, total bilirubin and chloride and decreases in the body weight gain, food consumption and liver weight at the dose levels of above 10 mg/kg/day. Under the present experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz was considered to be 3 mg/kg/day.

• 한방안이비인후피부과학회지
• /
• 제20권3호
• /
• pp.43-50
• /
• 2007

Background and Objectives : The aim of this study was to investigate the anti-oxidant and anti-inflammatory effects of the Taglisodog-eum(TSE) extract on the RAW264.7 cell Methods : The RAW264.7 cell was cultured using Dulbecco's modified Eagle's medium(DMEM, USA), including the 10% fetal-bovine serum(FBS; Sigma, USA) in a $37^{\circ}C$, 5% CO2 incubator. Results : The anti-oxidant ability of TSE were dose-dependantly increased. The LPS-induced IKK, iNOS and COX-2 mRNA expression were dose-dependantly decreased in the RAW264.7 cells treated with TSE. $NF-kB$ activation was suppressed. Conclusion : The findings in this study show that TSE has anti-oxidant and anti-inflammatory effects, such as the inhibition of $NF-kB$ activity.

• Toxicological Research
• /
• 제14권2호
• /
• pp.193-203
• /
• 1998

The toxicity of DA-125. a new anthracycline anticancer agent, on the male reproductive system was studied in Sprague-Dawley rats. Forty male rats were rando$m\ell$y assigned to Jour groups with ten rats in each group and given single intraveneous doses of DA-125 at dose levels of 0. 12.5. 25. and 50 mg/kg body weight. On day 56 after treatment the animals were allowed to mate. and their male reproductive Junctions and organs were examined in detail. Copulated females were sacrificed on day 20 of gestation for examination of embryo-fetal development. One out of ten rats in the 50 mg/kg group died on day 12 after treatment. Clinical signs such as emaciation. sedation, anorexia. swelling. dark material around eye. alopecia. and diarrhea were observed in the 25 and/or 50 mg/kg groups. Reduction in the body weight gain. decrease in the absolute weights of testes. epididymis and seminal vesicles. and/or decrease in the number of testicular sperm heads were also found. Although histopathological changes such as atrophy of seminiferous tubules. loss or decrease of spermatogenic cells. exfoliation of spermatogenic cells. vacuolization of Sertoli cells. decrease of sperm. and/or increase of necrotic spermatogenic cells in epididymal ducts were observed. no adverse effects on the motility and morphology of epididymal sperm. copulation index. fertility index. and embryo-fetal development were detected in the 25 and 50 mg/kg groups. There were no evidences of male reproductive toxicity in the 12.5 mg/kg group. These results show that single intravenouse doses of DA-125 produce significant dose-related testicular atrophy. histopathological changes. and oligozoospermia in rats and $LD_{10}$ for DA-125 appears to be 50 mg/kg body weight.

• Biomolecules & Therapeutics
• /
• 제11권2호
• /
• pp.85-90
• /
• 2003

Microtubule-binding molecules have been developed as anti-cancer agents to overcome the toxicities of current chemotherapeutics and also have potential for use as anti-angiogenic agents. In this work, we examined the effect of novel triazine compounds, Tubulyzines (microTUBUle LYsing triaZINE), derived from the orthogonal synthesis of a triazine library, on endothelial progenitor cell differentiation. When mononuclear cells isolated from human cord blood were cultured on fibronectin-coated plates for 7 days, all the Tubulyzine compounds A, B, and C (TA, TB, and TC) tested decreased the number of adherent cells in a dose-dependent manner in a coo. centration ranges of 2-5 to $80\mu\textrm{M}$. TA ($IC_{50}$=$20\mu\textrm{M}$) showed slightly more potent activity than TB and TC. Adherent cells treated with TA also exhibited a lower level of ability to ac-LDL uptake, with low ratios of positive cells out of total adherent cells, in a dose-dependent manner and weak expression of endothelial lineage markers, KDR, CD31, and vWF at $20\mu\textrm{M}$. Therefore, these results suggest that tubulyzine A (TA) can be effectively used for the inhibition of new vessel growth by inhibiting differentiation of endothelial progenitor cells.

• BMB Reports
• /
• 제28권6호
• /
• pp.515-522
• /
• 1995

The effects of the thyroid hormone ($T_3$) on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were evaluated in a baby hamster kidney cell line, C100. The cells cultured in MEM were supplemented with 10% thyroid hormone-depleted fetal bovine serum (THDS-MEM) and had a 82.5% lower level of HMG-CoA reductase activity than the cells grown in a medium supplemented with fetal bovine serum (FBS-MEM). When $T_3$ was supplemented to THDS-MEM, the reduction of the reductase activity was blocked in a dose-dependent manner. In the cells grown in THDS-MEM containing $T_3$ at a concentration of $10^{-6}$ M, the level of HMG-CoA reductase activity was 91.8% relative to the cells grown in FBS-MEM. These changes in HMG-CoA reductase activity seemed to be at least partly due to the changes of HMG-CoA reductase mRNA levels. The level of HMG-CoA reductase mRNA in cells incubated in THDS-MEM decreased to 76.2% relative to the cells grown in FBS-MEM, while the level of reductase mRNA in cells incubated in THDS-MEM containing $T_3$ at a concentration of $10^{-6}$ M increased to 243.4% relative to the cells grown in FBS-MEM. The increase of HMG-CoA reductase mRNA level after $T_3$ treatment may have been due to the increased stability of reductase mRNA, because the transcriptional rate of the reductase gene did not change significantly in the presence or absence of $T_3$. These results indicate that $T_3$ stabilizes HMG-CoA reductase mRNA at the posttranscriptional level and regulates HMG-CoA reductase activity in a dose-dependent manner.

• Environmental Analysis Health and Toxicology
• /
• 제26권
• /
• pp.6.1-6.8
• /
• 2011

Objectives: The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats. Methods: MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined. Results: All animals survived to the end of the study. A decrease in thymus weight was observed in the highest dose group. However, maternal body weight, food consumption, serum biochemical parameters, and oxidant-antioxidant balance in the kidneys were not affected by treatment with MWCNTs. No treatment-related differences in gestational index, embryo-fetal mortality, or fetal and placental weights were observed between treated and control groups. Conclusions: The results show that 14-day repeated oral dosing of MWCNTs during pregnancy induces minimal maternal toxicity at 1000 mg/kg/day in rats. Under these experimental conditions, the no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1000 mg/kg/day for embryonic development.

• 한국발생생물학회지:발생과생식
• /
• 제19권4호
• /
• pp.167-180
• /
• 2015

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.

• BMB Reports
• /
• 제42권8호
• /
• pp.493-499
• /
• 2009

MicroRNAs (miRs) are a family of small noncoding RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation. In this paper we have first analyzed by microarray the miR-profile in erythroid precursor cells from one normal and two thalassemic patients expressing different levels of fetal hemoglobin (one of them displaying HPFH phenotype). The microarray data were confirmed by RT-PCR analysis, and allowed us to identify miR-210 as an highly expressed miR in the erythroid precursor cells from the HPFH patient. When RT-PCR was performed on mithramycin-induced K562 cells and erythroid precursor cells, miR-210 was found to be induced in time-dependent and dose-dependent fashion, together with increased expression of the fetal $\gamma$-globin genes. Altogether, the data suggest that miR-210 might be involved in increased expression of $\gamma$-globin genes in differentiating erythroid cells.