• Title/Summary/Keyword: chronic toxicity

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Neuroprotective Effects of Herbal Ethanol Extracts from Gynostemma pentaphyllum on L-DOPA Therapy in 6-hydroxydopamine-lesioned Rat Model of Parkinson's Disease (돌외 에탄올 추출물 엑스가 6-hydroxydopamine-유도 파킨슨병 백서 모델에서의 L-DOPA 요법에 미치는 영향)

  • Suh, Kwang-Hoon;Choi, Hyun-Sook;Shin, Keon-Seong;Hwang, Bang-Yeon;Lee, Myung-Koo
    • Korean Journal of Pharmacognosy
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    • v.42 no.4
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    • pp.341-347
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    • 2011
  • The neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease treated with L-DOPA were investigated. Rats were prepared for the Parkinson's disease model by 6-OHDA-lesioning for 14 days. The rats were then treated with L-DOPA (10 and 20 mg/kg) with or without the oral administration of GP-EX (30 mg/kg, daily) for 28 days. L-DOPA (20 mg/kg) treatment for 28 days enhanced dopaminergic neuronal cell death in 6-OHDA-lesioned rat groups, but L-DOPA (10 mg/kg) did not. However, the oral administration of GP-EX (30 mg/kg) for 28 days ameliorated the enhanced neurotoxic effects induced by chronic L-DOPA treatment in 6-OHDA-lesioned rat groups by increasing tyrosine hydroxylase (TH)-immunohistochemical staining and the number of TH-immunopositive cells surviving in the substantia nigra. In addition, GP-EX administration (30 mg/kg) for 28 days recovered the levels of dopamine and norepinephrine of the striatum in 6-OHDA-lesioned rat groups, which were markedly reduced by L-DOPA treatment (20 mg/kg). GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting in rats during the 28-day treatment period. These results suggest that GP-EX has protective functions against chronic L-DOPA-induced neurotoxic reactions in dopaminergic neurons in the 6-OHDA-lesioned rat model of Parkinson's disease. Therefore, GP-EX may be beneficial in the prevention of adverse symptoms in parkisonian patients.

Basic Physiological Research on the Wing Flapping of the Sweet Potato Hawkmoth Using Multimedia

  • Nakajima, Isao;Yagi, Yukako
    • Journal of Multimedia Information System
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    • v.7 no.2
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    • pp.189-196
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    • 2020
  • We have developed a device for recording biological data by inserting three electrodes and a needle with an angular velocity sensor into the moth for the purpose of measuring the electromyogram of the flapping and the corresponding lift force. With this measurement, it is possible to evaluate the moth-physiological function of moths, and the amount of pesticides that insects are exposed to (currently LD50-based standards), especially the amount of chronic low-concentration exposure, can be reduced the dose. We measured and recorded 2-channel electromyography (EMG) and angular velocity corresponding to pitch angle (pitch-like angle) associated with wing flapping for 100 sweet potato hawkmoths (50 females and 50 males) with the animals suspended and constrained in air. Overall, the angular velocity and amplitude of EMG signals demonstrated high correlation, with a correlation coefficient of R = 0.792. In contrast, the results of analysis performed on the peak-to-peak (PP) EMG intervals, which correspond to the RR intervals of ECG signals, indicated a correlation between ΔF fluctuation and angular velocity of R = 0.379. Thus, the accuracy of the regression curve was relatively poor. Using a DC amplification circuit without capacitive coupling as the EMG amplification circuit, we confirmed that the baseline changes at the gear change point of wing flapping. The following formula gives the lift provided by the wing: angular velocity × thoracic weight - air resistance - (eddy resistance due to turbulence). In future studies, we plan to attach a micro radio transmitter to the moths to gather data on potential energy, kinetic energy, and displacement during free flight for analysis. Such physiological functional evaluations of moths may alleviate damage to insect health due to repeated exposure to multiple agrochemicals and may lead to significant changes in the toxicity standards, which are currently based on LD50 values.

LJ-2698, an Adenosine A3 Receptor Antagonist, Alleviates Elastase-Induced Pulmonary Emphysema in Mice

  • Boo, Hye-Jin;Park, So Jung;Noh, Myungkyung;Min, Hye-Young;Jeong, Lak Shin;Lee, Ho-Young
    • Biomolecules & Therapeutics
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    • v.28 no.3
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    • pp.250-258
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    • 2020
  • Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A3 receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A3 receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

Evaluation of analgesic and antiinflammatory activity of Ophiorrhiza nicobarica, an ethnomedicine from Nicobar Islands, India

  • Chattopadhyay, Debprasad;Das, Sonali;Mandal, Asit Baran;Arunachalam, G;Bhattacharya, SK
    • Advances in Traditional Medicine
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    • v.7 no.4
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    • pp.395-408
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    • 2007
  • This study reports the analgesic, anti-inflammatory and membrane-stabilizing property of alcoholic extract of Ophiorrhiza nicobarica (ON), a wild herb, used as an anti-infective ethnomedicine of Nicobarese and Shompen tribes of Great Nicobar Island, India. We for the first time investigated the analgesic and antiinflammatory potential of this herb in acute, subacute and chronic model of inflammation in Swiss albino mice and Wistar albino rats, along with sheep RBC-induced sensitivity and membrane stabilization. The acetic acid induced writhing, tail flick and tail immersion tests are used as a model for evaluating analgesic activity; while the carrageenin-induced paw oedema was used as the model for acute inflammation, dextran-induced oedema as sub-acute and cotton-pellateinduced granuloma as chronic inflammatory model. The probable mode by which ON mediate its effect on inflammatory conditions was studied on sheep RBC-induced sensitivity and membrane stabilization. The in vitro results revealed that the ON extract possesses significant (P < 0.05) dose dependent analgesic and antiinflammatory activity at 200 and 300 mg/kg and its fractions at 50 mg/kg, p.o. respectively, compared to the control groups. However, the extract failed to exhibit membrane-stabilizing property as it unable to reduce the level of haemolysis of RBC exposed to hypotonic solution. The acute toxicity studies of ON extract in rats and mice revealed that the extract was nontoxic even up to 3.0 g/kg body weight of the animals, with a high safety profile. We have isolated ursolic acid, ${\beta}$-sitosterol and harmaline respectively, from the bioactive part of the extract. The results indicated that the O. nicobarica is indeed beneficial in primary health care, and suggest that its anti-inflammatory activity may not be related to membrane-stabilization.

Health Risk Assessment and Analysis on the Volatile Organic Compounds in Some Workplace (모작업장에서 휘발성 유기오염물질의 분석과 근로자들의 건강위해성 평가)

  • Lee, Hyo-Min;Kim, Myung-Soo;Choi, Shi-Nai;Yoon, Eun-Kyung;Park, Jong-Sei
    • Journal of Preventive Medicine and Public Health
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    • v.30 no.3 s.58
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    • pp.530-539
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    • 1997
  • This study was conducted to assess the health risk on the volatile organic compounds such as toluene, xylene, and styrene in painting workplace. It was monitored through personal air sampling during working time in selected 5 workplaces and analysed using gas chromatography. For the settlement of exposure situation, there were regarded working conditions such as working hours, yearly working days, and working years. Also, Monte-Carlo simulation was used for the induction of hazard index using toxicity value from IRIS(Integrated risk information system) database. The results of risk assessment were summarized as follows. 1. The air concentration of toluene was $7.096{\pm}15,644ppm,\;2.586{\pm}4.275ppm\;for\;xylene,\;1.914{\pm}5.320ppm$ for styrene in blast painting workplaces. The level of toluene was different significantly compared with the level of xylene and styrene. 2. Computated chronic daily intake values of 95th percentile on toluene, xylene and styrene treated by Monte-Carlo simulation were 9.616, 3.567, 2.782 mg/kg/day, respectively. 3. Computated hazard index values of 75th percentile on toluene, xylene and styrene treated by Monte-Carlo simulation were 3.5, 1.0 and 1.6, respectively. Adverse health effects on the toluene, xylene and styrene would be expected by working exposure in selected 5 workplaces since the hazard indices of three compounds were exceeded 1 in the surroundings of 75th percentile though having the low emerged frequency.

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Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity

  • Ji-Hye Jung;Se-Ran Yang;Woo Jin Kim;Chin Kook Rhee;Seok-Ho Hong
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.1
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    • pp.52-64
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    • 2024
  • Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

Aflatoxin B1-induced oxidative stress in canine small intestinal cells

  • Hyun-Woo Cho;Kangmin Seo;Min Young Lee;Sang-Yeob Lee;Kyoung Min So;Ki Hyun Kim;Ju Lan Chun
    • Journal of Animal Reproduction and Biotechnology
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    • v.39 no.2
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    • pp.105-113
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    • 2024
  • Background: Aflatoxin B1 (AFB1) is a toxic metabolite generated by Aspergillus species and is commonly detected during the processing and storage of food; it is considered a group I carcinogen. The hepatotoxic effects, diseases, and mechanisms induced by AFB1 owing to chronic or acute exposure are well documented; however, there is a lack of research on its effects on the intestine, which is a crucial organ in the digestive process. Dogs are often susceptible to chronic AFB1 exposure owing to lack of variation in their diet, unlike humans, thereby rendering them prone to its effects. Therefore, we investigated the effects of AFB1 on canine small intestinal epithelial primary cells (CSIc). Methods: We treated CSIc with various concentrations of AFB1 (0, 1.25, 2.5, 5, 10, 20, 40, and 80 μM) for 24 h and analyzed cell viability and transepithelial-transendothelial electrical resistance (TEER) value. Additionally, we analyzed the mRNA expression of tight junction-related genes (OCLN, CLDN3, TJP1, and MUC2), antioxidant-related genes (CAT and GPX1), and apoptosis-related genes (BCL2, Bax, and TP53). Results: We found a significant decrease in CSIc viability and TEER values after treatment with AFB1 at concentrations of 20 μM or higher. Quantitative polymerase chain reaction analysis indicated a downregulation of OCLN, CLDN3, and TJP1 in CSIc treated with 20 μM or higher concentrations of AFB1. Additionally, AFB1 treatment downregulated CAT, GPX1, and BCL2. Conclusions: Acute exposure of CSIc to AFB1 induces toxicity, and exposure to AFB1 above a certain threshold compromises the barrier integrity of CSIc.

Novel Algicidal Substance (Naphthoquinone Group) from Bio-derived Synthetic Materials against Harmful Cyanobacteria, Microcystis and Dolichospermum (유해 남조류 Microcystis와 Dolichospermum에 대하여 선택적 제어가 가능한 생물유래 살조물질 (Naphthoquinone 계열))

  • Joo, Jae-Hyoung;Cho, Hoon;Han, Myung-Soo
    • Ecology and Resilient Infrastructure
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    • v.3 no.1
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    • pp.22-34
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    • 2016
  • We developed a biologically-derived substance naphthoquinone (NQ) derivate for the eco-safe mitigation of harmful cyanobacteria blooms such as Microcystis and Dolichospermum. NQ was reacted with various substituents ($R_n$) to produce different NQ derivatives. We tested a total of 92 algicidal compounds based on the algicidal activity of Microcystis and Dolichospermum. 22 compounds of NQ were selected as candidates (algicidal activity >80% at $1{\mu}M$). Among them, NQ 40 compound showed the highest algicidal activity of 99.6% and 100% at the optimal concentration of $1{\mu}M$ on Microcystis and Dolichospermum, respectively. No algicidal effects of NQ 40 ($1{\mu}M$) were observed against non-target algae such as Stephanodiscus, Cyclotella and Peridinium. According to the results of acute eco-toxicity assessment, the $EC_{50}$ values of NQ 40 compound for Selenastrum capricornutum and Daphnia magna were 3.2 and $14.5{\mu}M$, respectively, and the $LC_{50}$ for Danio rerio was $15.7{\mu}M$. In addition, for D. magna chronic eco-toxicity assessment, no toxicity toward survival, growth and reproduction was observed. Therefore, we suggested the NQ 40 ($1{\mu}M$) compound as an alternative eco-safe algicidal substance to effectively mitigate harmful cyanobacteria blooms.

Trend of Multigenerational Transfer and Toxicity Studies Using Nanomaterials (나노물질을 이용한 다세대전이 및 독성 연구 추세)

  • Moon, Jongmin;An, Youn-Joo
    • Journal of Korean Society of Environmental Engineers
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    • v.38 no.7
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    • pp.395-401
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    • 2016
  • Nano-saftey has become an emerging issue recently, because of the broad use of nanomaterials in nano-industries and commercial areas. For a sustainable development in the nano-industry, active studies on nano-safety should be executed, especially on the potential risks in engineered nanomaterials (ENMs). Although acute and chronic assessments of nanomaterials have been extensively studied in many studies, multigenerational studies are very scarce. Overall, multigenerational studies have progressed as two different trends, studying post-generational effects or trans-generation effects. This study intended to suggest further nano-safety studies based on the trends and limitations of current ones. Through a comparative analysis, we investigated peer-reviewed multigenerational studies that used nanomaterials. Thirteen studies on post-generation effects confirmed generational nano-toxicity via several bioassays, such as mortality, fertility, and behavioral assays. Seven studies on trans-generation effects demonstrated nanomaterial pathways to next generations, using imaging techniques. Until now, mechanisms for post-generational nano-toxicity has been rarely proposed. Thus, we propose that complementary studies on such mechanisms are imperative for future studies.

Outcome of postoperative radiotherapy following radical prostatectomy: a single institutional experience

  • Lee, Sea-Won;Hwang, Tae-Kon;Hong, Sung-Hoo;Lee, Ji-Youl;Chung, Mi Joo;Jeong, Song Mi;Kim, Sung Hwan;Lee, Jong Hoon;Jang, Hong Seok;Yoon, Sei Chul
    • Radiation Oncology Journal
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    • v.32 no.3
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    • pp.138-146
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    • 2014
  • Purpose: This single institutional study is aimed to observe the outcome of patients who received postoperative radiotherapy after radical prostatectomy. Materials and Methods: A total of 59 men with histologically identified prostate adenocarcinoma who had received postoperative radiation after radical prostatectomy from August 2005 to July 2011 in Seoul St. Mary's Hospital of the Catholic University of Korea, was included. They received 45-50 Gy to the pelvis and boost on the prostate bed was given up to total dose of 63-72 Gy (median, 64.8 Gy) in conventional fractionation. The proportion of patients given hormonal therapy and the pattern in which it was given were analyzed. Primary endpoint was biochemical relapse-free survival (bRFS) after radiotherapy completion. Secondary endpoint was overall survival (OS). Biochemical relapse was defined as a prostate-specific antigen level above 0.2 ng/mL. Results: After median follow-up of 53 months (range, 0 to 104 months), the 5-year bRFS of all patients was estimated 80.4%. The 5-year OS was estimated 96.6%. Patients who were given androgen deprivation therapy had a 5-year bRFS of 95.1% while the ones who were not given any had that of 40.0% (p < 0.01). However, the statistical significance in survival difference did not persist in multivariate analysis. The 3-year actuarial grade 3 chronic toxicity was 1.7% and no grade 3 acute toxicity was observed. Conclusion: The biochemical and toxicity outcome of post-radical prostatectomy radiotherapy in our institution is favorable and comparable to those of other studies.