• Title/Summary/Keyword: sub-acute toxicity

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Anti-oxidative, Acetylcholinesterase Inhibitory Activities and Acute Toxicity Study of Nepeta sibirica L.

  • Gonchig Enkhmaa;Gendaram Odontuya;Erdenetsogt Purevdorj;Munkhbat Nomin;Gansukh Enkhjin;Tserendash Chimgee;Chultemsuren Yeruult
    • Natural Product Sciences
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    • v.29 no.2
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    • pp.74-82
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    • 2023
  • Nepeta sibirica L. or Siberian catmint is a medicinal plant species used in Mongolian traditional medicine for curing human different disorders and veterinary practices. The previous study of the whole plant concentrated on the determination of its essential oil composition and reported that the major ones are sesquiterpenes, including nepetalactone. The aim of this study was to reveal a new biological activity of the above-ground parts of N. sibirica L. and compare the activity of different extracts correlating with the content of biologically active compounds and evaluate their toxicity. For this purpose, anti-oxidative and acetylcholinesterase inhibitory activities of the above-ground parts of N. sibirica L. aqueous and ethanol (EtOH) (40%, 70%) extracts were assayed spectrophotometrically. The aqueous extract showed positive anti-oxidative activity by both tested DPPH and FRAP assays with IC50 134.24 ± 1.42 mg/mL and FRAP value 1385.15 ± 8.12 µmol/L at 200 ㎍/mL, in contrast to 40% and 70% EtOH extracts. The 70% EtOH extract presented the highest acetylcholinesterase inhibitory activity (IC50 77.29 ± 0.38 mg/mL) followed by 40% EtOH extract (176.72 ± 0.35 mg/mL) and aqueous extract (275.41 ± 0.23 mg/mL). Total phenolics were found to be gallic acid equivalent, % 3.74 ± 0.05 (70% EtOH), 3.94 ± 0.04 (40% EtOH), and 3.79 ± 0.16 (aqueous), whereas the total flavonoids as a rutin equivalent, % as 2.01 ± 0.12, 1.44 ± 0.17 and 1.99 ± 0.02, each. The aqueous extract showed the best anti-oxidative and lowest activity against the acetylcholinesterase; however, the 70% EtOH extract showed the opposite effects than that of the aqueous. No mortality incidence was visible at various doses, indicating that the oral median lethal dose of aqueous and 70% EtOH extracts were considered greater than 5000 mg/kg. N. sibirica L. belongs to the non-toxic category of the OECD 423 classification.

Caenorhabditis elegans as a Biological Model for Multilevel Biomarker Analysis in Environmental Toxicology and Risk Assessment

  • Choi, Jin-Hee
    • Toxicological Research
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    • v.24 no.4
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    • pp.235-243
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    • 2008
  • While in some instances, loss of diversity results from acute toxicity (e.g. major pollution incidents), in most cases it results from long-term sub-lethal effects that alter the relative competitive ability and fitness of certain organisms. In such cases the sub-lethal effects will cause a physiological response in the organism that ultimately leads to community level changes. Very sensitive tools are now available to study sub-lethal responses at the molecular level. However, relating such laboratory measurements to ecological effects represents a substantial challenge that can only be met by investigation at all scales (molecular, individual organism and community level) with an appropriate group of organisms. Among the various in vertebrates which can be used as model organisms in such a way, the soil nematode, Caenorhabditis elegans appear to be a promising biological model to diagnose environmental quality. This paper reviews the current status of multilevel biomarkers in environmental toxicology, and C. elegans as promising organisms for this approach.

Anti-inflammatory activity of aqueous methanolic extract of Swietenia mahagoni (L.) Jacq. (Meliaceae) leaves

  • Roy, S;Besra, SE;Banerjee, B;Mukherjee, J;Vedasiromoni, JR
    • Advances in Traditional Medicine
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    • v.9 no.1
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    • pp.74-82
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    • 2009
  • Pharmacological investigations were carried out with aqueous methanolic extract (AME) of Swietenia mahagoni (L.) Jacq. (Meliaceae) leaves. Acute toxicity studies revealed that the $LD_{50}$ dose of AME was 600 mg/kg, i.p. AME was found to possess significant anti-inflammatory activity in acute, sub-chronic and chronic models of inflammation. AME selectively inhibited cyclooxygenase (COX)-2 activity, which is involved in arachidonic acid metabolism and biosynthesis of prostaglandins under inflammatory conditions. Treatment with AME significantly enhanced total peritoneal cell count and the number of macrophages in normal mice, which revealed that AME may also alter the immune response along with its anti-inflammatory effect. The saponins or the alkaloids present in AME may be responsible for the anti-inflammatory activity.

Ecotoxicity Evaluation of PFCs using Marine Invertebrate, Sea Urchin (Mesocentrotus nudus) (둥근성게(Mesocentrotus nudus)를 이용한 과불화화합물의 생태독성평가)

  • Choi, Hoon;Lee, Ju-Wook;Lee, Seung-Min;Jeon, Hyung-Ju;Heo, Seung;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.6 no.2
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    • pp.80-87
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    • 2021
  • In this study, the toxic effects of PFOA and PFOS potassium salt on Mesocentrotus nudus using 10 min-fertilization rate and 48 h-normal embryogenesis were confirmed through the calculation of toxicity values such as Non-observed effective concentration, Low-observed effective concentration, and 50% of effective concentration. The case of 10 min-fertilization rate and 48 h-normal embryogenesis showed the concentration-dependent reduction pattern when exposed to PFOA and PFOS potassium salt, in tested concentration, respectively. The EC50 values of 10 min-fertilization rates for PFOA and PFOS potassium salt were 1346.43 mg/l and 536.18 mg/l, respectively, and the EC50 values of 48 h-normal embryogenesis were 42.67 mg/l and 17.81 mg/l, respectively. Both toxicity test methods showed high toxicity sensitivity to PFOS potassium salt. Recent studies have shown that the concentration of PFOA and PFOS in the marine environment has continuously decreased, and it is not enough to show acute toxicity to sea urchin. However, PFOA and PFOS have a very long half-life and can accumulate throughout the life of marine life, so it is still observed at a high concentration in shellfish. Therefore, a study on chronic toxicity through the whole-life cycle of marine organisms in coastal environments should be needed.

Single Oral Dose Toxicity Study of WK-38 in Rats (랫트에서 WK-38의 단회경구투여 독성에 관한 연구)

  • Chang, Bo-Yoon;Kim, Yoon-Chul;Lee, An-Sook;Kang, Dae-Gill;Lee, Ho-Sub;Kim, Sung-Yeon
    • Journal of Food Hygiene and Safety
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    • v.22 no.2
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    • pp.93-98
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    • 2007
  • Acute toxicity of WK-38, a herbal preparation for the atherosclerosis, was examined using male and female Sprague-Dawley rats. WK-38 is composed of Rhei Rhizoma, Magonoliae Cortx, Moutan Cortex Radicis. Rats were treated with the WK-38 intragastrically at 0 mg/kg, 5 mg/kg, 50 mg/kg, 500 mg/kg or 2,000 mg/kg and observed for two weeks. No mortality was observed at the doses used. Abnormal clinical signs such as eye bleeding, nasal bleeding and hyperemia had been shown temporary after administration. All rats were appeared to be healthy and normal during the 2 week observation. Also there was no difference in net body weight gain, gross pathological findings, and urine analysis among the groups rats treated with different doses of the WK-38.

Alterations of Antioxidant Status and Mitochondrial Succinate Dehydrogenase Activity in the Liver of Wistar Strain Albino Rats Treated with by Ethanol Extracts of Annona senegalensis Pers (Annonaceae) Stem Bark

  • Adisa, Rahmat Adetutu;Kolawole, Naimat;Sulaimon, Lateef A.;Brai, Bathlomew;Ijaola, Abraham
    • Toxicological Research
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    • v.35 no.1
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    • pp.13-24
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    • 2019
  • Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The $LD_{50}$ value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.

Efficacy of Postoperative Radiotherapy Using Modern Techniques in Patients with Retroperitoneal Soft Tissue Sarcoma

  • Kim, Hyun Ju;Koom, Woong Sub;Cho, Jaeho;Kim, Hyo Song;Suh, Chang-Ok
    • Yonsei Medical Journal
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    • v.59 no.9
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    • pp.1049-1056
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    • 2018
  • Purpose: Local recurrence is the most common cause of failure in retroperitoneal soft tissue sarcoma patients after surgical resection. Postoperative radiotherapy (PORT) is infrequently used due to its high complication risk. We investigated the efficacy of PORT using modern techniques in patients with retroperitoneal soft tissue sarcoma. Materials and Methods: Eighty patients, who underwent surgical resection for non-metastatic primary retroperitoneal soft tissue sarcoma at the Yonsei Cancer Center between 1994 and 2015, were retrospectively reviewed. Thirty-eight (47.5%) patients received PORT: three-dimensional conformal radiotherapy in 29 and intensity-modulated radiotherapy in nine patients. Local failure-free survival (LFFS), overall survival (OS), and RT-related toxicities were investigated. Results: Median follow-up was 37.1 months (range, 5.8-207.9). Treatment failure occurred in 47 (58.8%) patients including local recurrence in 33 (41.3%), distant metastasis in eight (10%), and both occurred in six (7.5%) patients. The 2-year and 5-year LFFS rates were 63.9% and 47.9%, respectively. The 2-year and 5-year OS rates were 87.5% and 71.1%. The 5-year LFFS rate was significantly higher in PORT group than in no-PORT group (74.2% vs. 24.3%, p<0.001). In multivariate analysis, PORT was the only independent prognostic factor for LFFS. However, there was no significant correlation between RT dose and LFFS. OS showed no significant difference between the two groups. Grade ${\leq}2$ acute toxicities were observed in 63% of patients, but no acute toxicity ${\geq}$ grade 3 was observed. Conclusion: PORT using modern technique markedly reduced local recurrence in retroperitoneal sarcoma patients, with low toxicity. The optimal RT technique, in terms of RT dose and target volume, should be further investigated.

Inhalation Toxicity of 1-Bromoprpane (1-BP)

  • Kim, Hyeon-Yeong;Lee, Jun-Yeon;Lim, Cheol-Hong;Chung, Yong-Hyun;Han, Jung-Hee;Jeong, Jae-Hwang;Lee, Sung-Bae;Jhoon, Yoon-Sook;Lee, Yong-Muk
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.126-126
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    • 2001
  • The purpose of this study was to investigate the acute(4 hrs) and repeated-dose(6 hrs a day, 5 days a week, 8 weeks) toxic effects of 1-bromopropane(1-BP) on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows ;(omitted)

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Toxicity Assessment and Establishment Acceptable Daily Intake of Penthiopyrad (펜티오피라드(Penthiopyrad)의 독성평가와 일일섭취허용량 설정)

  • Jeong, Mi-Hye;Hong, Soon-Sung;Park, Kyung-Hun;Kim, Chan-Sub;Park, Jae-Eup;Hong, Moo-Ki;Im, Moo-Hyeog;Kim, Young-Bum;Han, Bum-Seok;Han, Jeung-Sul
    • The Korean Journal of Pesticide Science
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    • v.14 no.4
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    • pp.478-489
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    • 2010
  • Penthiopyrad is a fungicide agent in types of pyrazole which is showing the effect of prevention in fungal disease and powdery mildew. In order to register this new pesticide, reports of acute toxicity and chronic toxicity by animal study were examined to set acceptable daily intake to evaluate hazards of consumers. Acute toxicity was low in toxic, and it did not have the effect of acute dermal toxicity, acute eye irritation, or skin sensitization. As the result of the study in chronic toxicity, the common effect of chemical appeared in the liver and thyroid which was proven as a toxic effect. Two-generation reproduction toxicity, genotoxicity, and prenatal development toxicity were not proven. As the result of carcinogenic study, increase of thyiroid follicular adenoma in the rat and the frequency of liver hepatocellar adenoma in mice were also increased. However, it was decided that the threshold value on the effect in chemicals could be controlled through study liver enzyme induction. Therefore, the ADI for penthiopyrad is 0.081 mg/kg/ bw/day, based on the NOAEL of 8.10 mg/kg bw/day of twelve-months dogs study and applying an uncertainty factor of 100.

Effect of 17β-estradiol on Ecdysteroid Pathway Related Genes in the Brackish Water Flea Diaphanosoma celebensis (17β-estradiol이 기수산 물벼룩의 Ecdysteroid 경로에 미치는 영향)

  • In, Soyeon;Yoo, Jewon;Cho, Hayoung;Lee, Young-Mi
    • Journal of Marine Life Science
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    • v.5 no.2
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    • pp.35-42
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    • 2020
  • 17β-estradiol (E2) is a natural hormone secreted by ovary, and continuously discharged from household and livestock wastewater into aquatic environment. Due to its strong estrogenic activity, it has adverse effects on development and reproduction in crustacean as an endocrine disrupting chemical. Although ecdysteroid signaling pathway play a key role in development in crustacean, little information on transcriptional modulation of ecdysteroid-related genes in response to E2 is available in small crustacean. Here, we investigated the acute toxicity of E2 to obtain 24-h LCx values in the brackish water flea Diaphanosoma celebensis. Time-dependent expression patterns of seven ecdysteroid pathway - related genes (CYP314a1, EcRA, EcRB, USP, ERR, Vtg, VtgR) were further examined using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR). As results, 24-h LC50 and LC10 values were 9.581 mg/l and 4.842 mg/l, respectively. The mRNA expression of CYP314a1, EcRA, USP, VtgR was significantly up-regulated at 12 or 24 h after exposure to E2. These findings indicate that E2 can affect their molting and reproduction by modulating the expression of ecdysteroid pathway - related in D. celebensis. This study will be useful for better understanding of molecular mode of action of endocrine disrupting chemicals on molting process in small crustacean.