• Title/Summary/Keyword: Comparative toxicity

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Effect of Corni Fructus on Testosterone Deficiency Syndrome in In vitro and In vivo (In-vitro와 In-vivo에서 산수유의 남성갱년기 개선효과)

  • Kim, Tae Muk;Jung, Ho Kyung;Jang, Ji Hun;Sim, Mi Ok;Lee, Mu Jin;Cho, Jung Hee;Cho, Hyun Woo
    • Korean Journal of Pharmacognosy
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    • v.47 no.3
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    • pp.264-272
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    • 2016
  • This study was carried out to evaluate the preventive effect of the Corni Fructus (SSU) 50 % EtOH extract (SSU-E50) against bisphenol A (BPA) toxicity in Leydig cells and improving testosterone deficiency syndrome in orchidectomized Sprague-Dawly (SD) rats. Antioxidant properties were measured by radical scavenging activity of SSU-E50 in ABTS assay and DPPH assay. Also, real-time polymerase chain reaction(real-time PCR) was performed to quantify the mRNA expression levels of antioxidant enzyme. SD rats were divided into eight group: normal, sham operation (Sham), orchidectomized (ORX), ORX treated with testosterone 1 mg/kg (Tes. 1), ORX treated with SSU water extract 100 mg/kg (SSU-A 100) and 300 mg/kg (SSU-A 300), ORX treated with SSU 50 % EtOH extract 100 mg/kg (SSU-E 100) and 300 mg/kg (SSU-E 300). On a comparative basis, the SSU showed better activity quenching ABTS with an IC50 value of 0.29 mg/ml and DPPH with an IC50 value of 0.33 mg/ml. Cell viability was evaluated by MTS assay as described not cytotoxic at the highest concentration of $500{\mu}g/ml$. Cytotoxicity of BPA showed in $200{\mu}M$, but definitely survived by treatment with SSU in Leydig cells. In addition, SSU increased the mRNA expression levels of antioxidant enzyme in BPA induced Leydig cells. Superoxide dismutase (SOD) level was slightly increased and malondialdehyde (MDA) level was decreased with SSU-A 100 in in-vivo. These results suggest that Corni Fructus extracts have the greatest property as a natural anti-oxidative and improves testosterone deficiency syndrome source.

Effect of Carbon Tetrachloride on the Changes of Xanthine Oxidase Activity in Rate Previously Fed Low or High Protein Diet (식이성 단백질 함량에 따른 흰쥐에 사염화탄소 투여가 Xanthine Oxidase활성에 미치는 영향)

  • 윤종국;이상일;신중규
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.20 no.6
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    • pp.527-537
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    • 1991
  • To evaluate an effect of liver xanthine oxidase on the induction of liver damage, carbon tetrachloride (CCl4) was intraperitoneally injected twice at 0.1ml/100g body weight to the rate fed a low (LP)or high protein diet(HP) while the control group fed LP or HP received only olive oil. The changing rate of liver xanthine oxidas activity was compared with that of a free radical generating enzyme, liver aniline hydroxylase and a scavenging enzyme, glutathions S-transferase activity between the rate fed a LP and those fed HP, and the two groups treated with CCl4. Concomitantly, the degree of liver damage which could be considered as the paramete for CCl4 metabolism in case of CCl4-intoxicated animal was observed in the present experimental conditions and the effect of allopurinol, xanthine oxidase inhibitor, on the CCl4-toxicity of rate liver was alos demostrated. On the other hand, the comparative effect of actinomycin D on the liver and serum xanthine oxidase of CCl4-treated rats fed HP with that of those fed LP and the kinetics of purifed liver enzyme from the liver of CCl4-treated rats fed HP was also compared with that of those fed LP to clarify the differences of xanthine oxidase activity between two groups. The increasing rate of liver weigth/body wt, serum levels of ALT and the decreasing rate of hepatic ALT activity and protein contents to each control group were higher in CCl4-treated rats fed HP than those fed LP. Under the animal models as indentified by the present data herein, the liver xanthine oxidase activity was higher in CCl4-treated rats fed HP than those fed LP, and the control group fed HP also showed the much higher activity xanthine oxidase than that fed LP, whereas there were no differences in the activity of hepatic aniline hydroxylase and glutathions S-transferase between the two group treated with CCl4. Although the hepatic aniline hydroxylase activity was somewhat higher in the rats fed HP than those fed LP, the increasing rate of liver xanthine oxidase to the rats fed LP was higher in those fed HP than that of liver aniline hydroxylase. The degree of liver damage identified such as liver weight and serum ALT activity was less in the CCl4-treated rats pretreated with allopurinol. These results suggest that even a system at which xanthine oxidase acts as well as the drug metabolizing enzyme may influence the acelatin of CCl4 metabolism. In addition, the purified liver xanthine oxidase from CCl4-treated rats fed HP showed decreased Km value when compared to its control group. The Km value of liver xanthine oxidase of CCl4-treated rats fed LP showed a similar Km value with its control group. Furthermore, the decreasing rate of liver and serum xanthine oxidase acitivity in CCl4-treated rats pretreated with actinomycin D to the CCl4-treated rats was higher in rats fed HP than in those fed LP. These results suggest that the inductino of xanthine oxidase in CCl4-treated rats fed HP may be greater than in those fed LP.

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A Comparative Study on the Effects of Pinellia ternata, Zingiber officinale and Sobanhatang on Reflux Esophagitis (역류성 식도염에 대한 반하(半夏), 생강(生薑), 소반하탕(小半夏湯)의 효과 비교)

  • Lee, Seul-hee;Baik, Tai-Hyeun
    • The Journal of Korean Medicine
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    • v.40 no.2
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    • pp.17-34
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    • 2019
  • Objectives: This study was carried out to observe and compare the effects of Pinellia ternata, Zingiber officinale and Sobanhatang on the reflux esophagitis induced by gastric fundus and pylorus ligation in mice with esomeprazole. Methods: Antioxidant effects were measured by DPPH radical scavenging activity at four different concentration of 0.125, 0.25, 0.5 and $1.0mg/102{\mu}{\ell}$. Zingiber officinale water extract(ZE), Pinellia ternata water extract(PE) and Sobanhatang water extract(SBE) and esomeprazole were treated orally for 14 days before gatric fundus and pylorus ligation. In the histochemistry, changes in suface mucous cells, muscle tissue and connective tissue in gastro esophageal junction(GEJ) and mast cell on the esophageal mucosa were observed. The change of Hemo oxygenase(HO)-1, ghrelin, gastrin and substance P in gastric body tissue were measured by immunohistochemistry. Results: DPPH radical scavenging activity exhibited concentration dependently increases in ZE, PE, SBE. ZE was significantly higher at all concentrations than PE. The gastric surface mucous cells were more in the treated group than in the reflux esophagitis elicited group(GE) in the order of PE, SBE, ZE and esomeprazole treateded group(PT, SBT, ZT, ET). Lower esophageal sphincter muscle damage and intercellular space in the GEJ were less in the treated group than GE. In the esophageal mucosa, the mast cell distribution and the migration of inflammatory cells were lower in the treateded troup than GE in order to ZT, SBT, PT and ET. The antioxidative enzyme, HO-1 was more in the order of ZT, SBT, control group, PT, ET than in GE. ZT was significantly higher than the other groups and SBT was significantly higher than ET. Ghrelin was found to be higher in ZT, ET, SBT and PT than in GE, and ZT was significantly higher than all other groups except ET. Gastrin showed the highest positivity in GE, and was lower in the order of ET, ZT, SBT, PT, and control group. Substance P was the highest in GE, and was lower in the order of ET, ZT, SBT, PT and control group, and PT were significantly lower than ET. Conclusion: ZT, PT and SBT showed superior antioxidative, anti-inflammatory and mucosal protective effects on mouse reflux esophagitis as compared with ET. In particular, ZE was more effective in antioxidant and gastric motility enhancement, while PE was more effective in mucosal protection and anti-inflammatory effects. Sobanhatang is expected to be effective treatment because it has advantages of both drugs and reduces toxicity.

Comparative Study on the Differentiation Effect of Adipogenesis in 3T3-L1 Preadipocyte by 65 Herbal Medicine Prescriptions (65종 한약처방이 3T3-L1 지방전구세포의 지방 분화에 미치는 효능 비교 연구)

  • Choi, Hye-Min;Yu, Byung-Woo;Kim, Min-Ju;Kim, Jung-Ok
    • Journal of Korean Medicine for Obesity Research
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    • v.20 no.2
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    • pp.78-87
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    • 2020
  • Objectives: To expand and provide information on the efficacy of herbal medicines, anti-obesity effects were evaluated. In many studies, plant-derived components with anti-obesity efficacies have been investigated for their potential inhibitory effects on 3T3-L1 preadipocyte cells. The purpose of this study was to investigate the anti-obesity effects of 65 herbal medicine in 3T3-L1 preadipocyte cells. Methods: Preferentially, 3T3-L1 cells were treated with 65 herbal medicines (500 ㎍/mL) during differentiation for 8 days. Next, 3T3-L1 cells were treated with selected herbal medicines at concentrations ranging from 50 to 200 ㎍/mL during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining. The expressions of genes related to adipogenesis were measured by reverse transcription polymerase chain reaction and Western blot analyses. Results: Among the 65 kinds of herbal medicines, 13 herbal medicines that been shown to be effective against the accumulation of lipid droplets were selected. Finally, selected Banhasasim-tang and Samhwangsasim-tang showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affecting cell toxicity. In addition, Banhasasim-tang and Samhwangsasim-tang significantly reduced the expression levels of several adipocyte marker genes including peroxisome proliferator activated receptor-γ and CCAAT/enhancer binding protein-α. Conclusions : These results suggest that the ability of Banhasasim-tang and Samhwangsasimtang has inhibited overall adipogenesis and lipid accumulation in the 3T3-L1 cells. Banhasasim-tang and Samhwangsasim-tang may be a promising medicine for the treatment of obesity and related metabolic disorders.

Affecting Factors of Lung Disease and Classification of Exposure Rating of Applicants for Injuries from Humidifier Disinfectants (가습기살균제 피해신청자들의 노출등급 분류 및 폐질환 발생 영향요인 분석)

  • Gihong, Min;Junghyun, Shin;Eun-Kyung, Jo;Dayoung, Jeong;Jiyoon, Ryu;Dongjun, Kim;Jaemin, Woo;Sungho, Bae;Jihun, Shin;Seula, Lee;Yoon-Hyeong, Choi;Wonho, Yang
    • Journal of Environmental Health Sciences
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    • v.48 no.6
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    • pp.324-330
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    • 2022
  • Background: Lung injuries due to exposure to humidifier disinfectants (HDs) were reported in 2011 in South Korea. As a result of the government's epidemiological investigation and toxicity test study, it was found that HDs caused health damage such as lung disease. Objectives: The purpose of this study was to classify HD exposure ratings and analyze the affecting factors that could identify the relationship with lung disease. Methods: Exposure assessment for HDs was conducted using a questionnaire during face-to-face interviews with the applicants. Ratings of high exposure (Class 1) and low exposure (Class 2) were cross-tabulated with clinical ratings (acceptable and unacceptable). Logistic regression analysis was carried out by setting the clinical rating of lung disease as a dependent variable and the socio-demographic and exposure characteristics obtained through the questionnaire as independent variables. Results: The concentration in air of polyhexamethylene guanidine (PHMG) was 71.96±107.47 ㎍/m3, and the exposure concentration was 15.21±23.28 ㎍/m3 . The exposure rating was overestimated with 97.1% of affected subjects having high exposure using margin of exposure (MOE), but only 9.9% matching the clinical class. In the overestimated group, it could be explained by the fact that the exposure time was long and the subjects had already recovered from damage symptoms. As a result of logistic regression analysis, ten variables were found to be significant influencing factors. Conclusions: A new exposure rating could be calculated based on the MOE, and factors affecting lung disease could be estimated through comparative evaluation with the clinical rating.

Comparative Study of the Neuroprotective Effect of Sihogyeji-tang, Sihosogan-tang, and Sihocheonggan-tang on an MPTP-Induced Parkinson's Disease Mouse Model (MPTP로 유도된 파킨슨병 생쥐 모델에 대한 시호계지탕, 시호소간탕, 시호청간탕의 신경세포 보호 효과 비교 연구)

  • Ji Eun Seo;Hanul Lee;Chang-Hwan Bae;Dong Hak Yoon;Hee-Young Kim;Seungtae Kim
    • Korean Journal of Acupuncture
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    • v.40 no.3
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    • pp.90-98
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    • 2023
  • Objectives : Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN). In a previous in vitro study, we demonstrated that Sihogyeji-tang (SG), Sihosogan-tang (SS), and Sihocheonggan-tang (SC) have the potential to be candidate medicines for PD. This study aimed to compare the neuroprotective effect of SG, SS, and SC using 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP)-induced PD mouse model. Methods : Eight-week-old male C57BL/6 mice were intraperitoneally administered with 30 mg/kg of MPTP for 5 days and orally administered SG, SS and SC for 12 days from the first MPTP injection. Motor function was assessed using the pole test and the rotarod test. Dopaminergic neuronal survival in the SN and striatum was evaluated through tyrosine-hydroxylase immunohistochemistry. Results : MPTP administration resulted in behavioral impairment and dopaminergic neuronal death in the SN and striatum. In the pole test, treatment with SG, SS, and SC alleviated the MPTP-induced motor dysfunction on day 5 and 12. In the rotarod test, SS and SG alleviated the MPTP-induced motor dysfunction on day 5, while only SS showed improvement on day 12. SS and SG significantly protected dopaminergic neurons in the SN from MPTP toxicity, and all three compounds (SG, SS, and SC) showed significant protection in the striatum. Notably, SS demonstrated superior efficacy in suppressing MPTP-induced motor dysfunction and dopaminergic neuronal death compared to SG and SC. Conclusions : These findings suggest that SS is the most effective formula among SG, SS, and SC for PD, indicating its potential role in the treatment of PD.

Role of Salmonella Typhimurium SlyA in Regulating the Expression of VirulenceFactors Related to Survival in Macrophages (대식세포 내 생존과 관련된 독성인자 발현 조절에서의 Salmonella Typhimurium SlyA의 역할)

  • Yeo bin Kim;Jeong-eun Baek;Yeon Ha Kim;Young Hee Kim;Ah Young Yoo;Ho Young Kang
    • Journal of Life Science
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    • v.34 no.2
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    • pp.79-85
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    • 2024
  • SlyA is known as a transcriptional regulator that regulates the expression of hemolysin (HlyE) in E. coli, a member of the Enterobacteriaceae family such as Salmonella. However, Salmonella has the slyA gene but lacks the hlyE gene. Then, because we were curious about the role of SlyA in Salmonella, we constructed and explored a mutant strain with a deletion of the slyA gene. S. Typhimurium CK295 (ΔslyA) was constructed using an allelic exchange approach. In a comparative analysis between the wild-type and the CK295 strain, no significant differences were observed in growth characteristics, motility, total protein analyses, and secreted protein analyses. However, the CK295 strain exhibited slightly reduced biofilm formation compared to the wild-type. Interestingly, as a result of comparing the survival ability in macrophages, the mutant strain showed a 60% decrease in survival ability compared to the wild-type. To evaluate toxicity in mice, mortality was measured after oral administration to 6-week-old BALB/c mice. As a result, the LD50 value of the CK295 (ΔslyA) was more than 100 times higher than that of wild-type S. Typhimurium 𝜒3339 in BALB/c. In conclusion, SlyA is presumed to regulate the expression of genes encoding virulence factors involved in the in vivo survival of Salmonella.

The Classification System and Information Service for Establishing a National Collaborative R&D Strategy in Infectious Diseases: Focusing on the Classification Model for Overseas Coronavirus R&D Projects (국가 감염병 공동R&D전략 수립을 위한 분류체계 및 정보서비스에 대한 연구: 해외 코로나바이러스 R&D과제의 분류모델을 중심으로)

  • Lee, Doyeon;Lee, Jae-Seong;Jun, Seung-pyo;Kim, Keun-Hwan
    • Journal of Intelligence and Information Systems
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    • v.26 no.3
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    • pp.127-147
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    • 2020
  • The world is suffering from numerous human and economic losses due to the novel coronavirus infection (COVID-19). The Korean government established a strategy to overcome the national infectious disease crisis through research and development. It is difficult to find distinctive features and changes in a specific R&D field when using the existing technical classification or science and technology standard classification. Recently, a few studies have been conducted to establish a classification system to provide information about the investment research areas of infectious diseases in Korea through a comparative analysis of Korea government-funded research projects. However, these studies did not provide the necessary information for establishing cooperative research strategies among countries in the infectious diseases, which is required as an execution plan to achieve the goals of national health security and fostering new growth industries. Therefore, it is inevitable to study information services based on the classification system and classification model for establishing a national collaborative R&D strategy. Seven classification - Diagnosis_biomarker, Drug_discovery, Epidemiology, Evaluation_validation, Mechanism_signaling pathway, Prediction, and Vaccine_therapeutic antibody - systems were derived through reviewing infectious diseases-related national-funded research projects of South Korea. A classification system model was trained by combining Scopus data with a bidirectional RNN model. The classification performance of the final model secured robustness with an accuracy of over 90%. In order to conduct the empirical study, an infectious disease classification system was applied to the coronavirus-related research and development projects of major countries such as the STAR Metrics (National Institutes of Health) and NSF (National Science Foundation) of the United States(US), the CORDIS (Community Research & Development Information Service)of the European Union(EU), and the KAKEN (Database of Grants-in-Aid for Scientific Research) of Japan. It can be seen that the research and development trends of infectious diseases (coronavirus) in major countries are mostly concentrated in the prediction that deals with predicting success for clinical trials at the new drug development stage or predicting toxicity that causes side effects. The intriguing result is that for all of these nations, the portion of national investment in the vaccine_therapeutic antibody, which is recognized as an area of research and development aimed at the development of vaccines and treatments, was also very small (5.1%). It indirectly explained the reason of the poor development of vaccines and treatments. Based on the result of examining the investment status of coronavirus-related research projects through comparative analysis by country, it was found that the US and Japan are relatively evenly investing in all infectious diseases-related research areas, while Europe has relatively large investments in specific research areas such as diagnosis_biomarker. Moreover, the information on major coronavirus-related research organizations in major countries was provided by the classification system, thereby allowing establishing an international collaborative R&D projects.

Clinical Efficacy of Belotecan (CKD-602), Newly Developed Camptothecin Analog, in the 2nd Line Treatment of Relapsed Small Cell Lung Cancer (재발된 소세포폐암환자에서 이차 약제로 사용되는 Belotecan (CKD-602)의 임상적 효용성)

  • Ban, Hee-Jung;Oh, In-Jae;Kim, Kyu-Sik;Ju, Jin-Yung;Kwon, Yong-Soo;Kim, Yu-Il;Lim, Sung-Chul;Kim, Young-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.2
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    • pp.93-97
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    • 2009
  • Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

Comparative Study of Toxic Effects of Anatase and Rutile Type Nanosized Titanium Dioxide Particles in vivo and in vitro

  • Numano, Takamasa;Xu, Jiegou;Futakuchi, Mitsuru;Fukamachi, Katsumi;Alexander, David B.;Furukawa, Fumio;Kanno, Jun;Hirose, Akihiko;Tsuda, Hiroyuki;Suzui, Masumi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.929-935
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    • 2014
  • Two types of nanosized titanium dioxide, anatase ($anTiO_2$) and rutile ($rnTiO_2$), are widely used in industry, commercial products and biosystems. $TiO_2$ has been evaluated as a Group 2B carcinogen. Previous reports indicated that $anTiO_2$ is less toxic than $rnTiO_2$, however, under ultraviolet irradiation $anTiO_2$ is more toxic than $rnTiO_2$ in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by $anTiO_2$ and $rnTiO_2$. Female SD rats were treated with $500{\mu}g/ml$ of $anTiO_2$ or $rnTiO_2$ suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with $anTiO_2$ or $rnTiO_2$ increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the $anTiO_2$ treated group compared to the $rnTiO_2$ treated group. Expression of $MIP1{\alpha}$ mRNA and protein in lung tissues treated with $anTiO_2$ and $rnTiO_2$ was also significantly up-regulated, with $MIP1{\alpha}$ mRNA and protein expression significantly lower in the $anTiO_2$ group than in the $rnTiO_2$ group. In cell culture of primary alveolar macrophages (PAM) treated with $anTiO_2$ and $rnTiO_2$, expression of $MIP1{\alpha}$ mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, $MIP1{\alpha}$ mRNA and protein expression was significantly lower in the $anTiO_2$ treated cultures compared to the $rnTiO_2$ treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with $anTiO_2$ had less effect on A549 cell proliferation compared to conditioned media from cultures treated with $rnTiO_2$. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated $anTiO_2$ and $rnTiO_2$. In conclusion, our results indicate that $anTiO_2$ is less potent in induction of alveolar macrophage infiltration, 8-OHdG and $MIP1{\alpha}$ expression in the lung, and growth stimulation of A549 cells in vitro than $rnTiO_2$.