• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.34-48
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• 1985

In vitro effects of nitrofurantoin, an antimicrobial agent for acute and chronic urinary tract infection, on the lung microsomal lipid peroxidation and the generation of reactive oxygen radicals were investigated to elucidate the biochemical mechanisms of its in vivopulmonary toxicity. The interaction of nitrofurantoin with porcine lung microsome resulted in significant lipid peroxidation. In addition, nitrofurantoin stimulated the generation of reactive oxygen radicals, $O^{-}_{2}{\cdot},\;H_2O_2$ as well as a highly reactive secondary oxygen species, $OH{\cdot}$. The stimulation of lipid peroxidation was inhibited not only by superoxide dismutase and catalase, but also by hydroxyl radical scavengers, mannitol and thiourea. Neither singlet oxygen $({^1}O_{2})$ was detected during the incubation of microsome with nitrofurantoin, nor lipid peroxidation was inhibited by singlet oxygen scavengers. When incubated anaerobically under the nitrogen atmosphere, the ability of nitrofurantoin to stimulatle lipid peroxidation was abolished. It appears that NADPH-dependent metaboliam of nitrofurantoin in pulmonary microsome under aerobic condition is accompanied by the stimulation of lipid peroxidation through the mediation of reactive oxygen radicals, particularly hydroxyl radical. It is strongly suggested from these results that the stimulation of pulmonary microsomal lipid peroxidation by the reactive oxygen radical may be a in vivo mechanism of pulmonary toxicity caused by nitrofurantoin.

• Radiation Oncology Journal
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• v.31 no.4
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• pp.206-215
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• 2013

Purpose: Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC. Materials and Methods: Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities. Results: The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 $Gy_{10}$. Median cumulative dose of the two courses of radiotherapy was 116.3 $Gy_{10}$ (range, 91.8 to 128.9 $Gy_{10}$) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient. Conclusion: Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.1
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• pp.41-48
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• 2012

The purpose of this study was to assess the antioxidant activity of vegetable extracts (pumpkin, aloe, and artichoke) containing Protaetia brevitarsis (PB) and the clinical and pathological changes in ICR mice after a single oral administration. The total polyphenol (TP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, total radical trapping antioxidant potential (TRAP), oxygen radical absorbance activity (ORAC), and single cell gel electrophoresis assay were done to measure their antioxidant activities. The effect of vegetable extracts containing PB in TP and the ORAC value was significantly higher than those without PB. In addition, all extracts had effective $DPPH{\cdot}$ scavenging and $ABTS{\cdot}+$ scavenging activities. The protective effect of vegetable extracts with/without PB on $H_2O_2$-induced DNA damage was found. In a single-dose toxicity study, mortality, body weight, physiological signs, and biochemical analysis were analyzed. Seventy mice were randomly assigned to 7 experimental groups and were administered three vegetable extracts with and without PB (2 g/kg). A full 14 days after administration, no mice mortality was observed in any group. Body weight, physiological signs, and biochemical analysis were never significantly different from those of the control group. Taken together, these findings indicate that vegetable extracts containing PB with antioxidant activities and safety could be applied as medicinal and edible resources in an industrial area.

• Toxicological Research
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• v.26 no.4
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• pp.293-300
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• 2010

tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in architectural coatings and industrial solvents. It has recently been exempted from the definition of a volatile organic compound (VOC) by the Air Resources Board (ARB). Since the use of TBAc as a substitute for other VOCs has increased, thus its potential risk in humans has also increased. However, its inhalation toxicity data in the literature are very limited. Hence, inhalation exposure to TBAc was carried out to investigate its toxic effects in this study. Adult male rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation exposure chamber (low dose, $2370\;mg/m^3$ (500 ppm); high dose, $9482\;mg/m^3$ (2000 ppm)). Shamtreated control rats were exposed to clean air in the inhalation chamber for the same period. The animals were killed at 2, 7, and 15 days after exposure. At each time point, body weight measurement, bronchoalveolar lavage fluid (BALF) analysis, histopathological examination, and biochemical assay were performed. No treatment-related abnormal effects were observed in any group according to time course. Based on those findings, the median lethal concentration ($LC_{50}$) of TBAc was over $9482\;mg/m^3$ in this study. According to the MSDS, the 4 h $LC_{50}$ for TBAc for rats is over $2230\;mg/m^3$. We suggested that this value is changed and these findings may be applied in the risk assessment of TBAc which could be beneficial in a sub-acute study.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.869-878
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• 1999

Intravesical instillation of the bacillus Calmentte-Gu$\acute{e}$rin(BCG), an attenuated strain of Mycobacterium bovis, is an approved method for the treatment of superficial bladder cancer. Because BCG is a living organism, the potential for infection exists. BCG is generally well tolerated, with complications in less than 5% of those treated with use of current practices. The most frequent symptoms of toxicity associated with intravesical BCG immunotherapy include bladder irritation, frequency, and dysuria. Systemic reactions are less common but more serious than local side effects, and include fever, chills, malaise, rash, hepatitis, pneumonitis, arthritis and sepsis. In rare cases, BCG treatment can result in a systemic infection that requires antituberculous therapy. The pulmonary toxicity that results from intravesical BCG treatment is generally characterized by one of two types : systemic allergic reaction with pulmonary reticulonodular opacities depicted on chest radiographs with cellular findings consisting of activated lymphocytes, and actual BCG mycobacteremia with a miliary pattern depicted on chest radiographs and granuloma formation which rarely results in positive acid-fast stain or culture results. Recently we experienced two types of pulmonary complications following intravesical BCG immunotherapy in patients with superficial bladder cancer. We report two cases with a review of literatures.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.6
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• pp.908-915
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• 1994

It was attempted to observe the antidotic effects of garlic on mercury intoxicated rat model in vivo. The experimental model group consists of garlic juice treated group (G), garlic juice-mercury treated group(MG), mercury treated group (M), and control group (basal diet), The garlic juice of 2% to the daily diet by weight was administered orally to G and MG groups, The single dose of 2.5mgHG/Kg per week was given orally to M and MG groups. the study was carried out for 4 weeks. The results of experiment were as follows. For the group of Mg, and the weight increasing rate was improved to about 30% compared to that of group M. Furthermore a general tonic efficay of garlic was observed in G group in term of increased weight gain rate (bout 15%) than control. In the biochemical studies of rat blood garlic showed effects on lowering the abnormally elevated GPT, GOT, uric acid creatinine value, and especially in lowering the BUN value of Hg treated rat that was selectively elevated in the case of impared renal function such as acute gromerulonephritis caused by Hg intoxication. In the analytical studies blood and renal Hg contents. HG group showed lower value (0.3, 0.33ppm) than that of M group (0.46, 0.51 ppm) Significant difference in reducing Hg level due to the antidotic effect of garlic was observed. In conclusion, it was revealed out from this research, the main principles of garlic, nonprotein sulfur amino acid (alliin) and sulfur compounds (allicin and diallyl disulfides) seem to almost certainly have an antidotic effect on mercury intoxication of rat in vivo.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.27 no.5
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• pp.529-534
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• 1994

The lethal concentration(LC50) of several micropollutants for three species of the fish Paralichthys olivaceus, Mugil cephalus and Sebastes schlegeli were determined by acute toxicity tests. For the determination of definitive test concentrations, the fish were exposed to three test material concentrations spaced at order-of-magnitude intervals based on a logarithmic ratio in range finding tests. LC50 was determined by five concentrations of test material in a geometric progression by means of range finding tests. The 96hr-LC50 values(mg/l) were estimated by the graphical interpolation of probability-logarithm transformations. These indicated that the order of sensitivities to three kind of micropollutants was Mugil cephalus > Paralichthys olivaceus > Sebastes schlegeli.

• Journal of the Korean Society of Food Science and Nutrition
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• v.18 no.3
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• pp.255-264
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• 1989

The results of toxicity test using mice and rats for ethanol extract of Bracken Fern collected in Kwang Ju area were shown as follows ; Up to the dose of 10g per kg of mice administered intraperitoneally there was no lethal toxicity so that it was impossible to calculate the median lethal dose $(LD_{50})$. For the first 7 days experiment all rats administered frond extract grouping in 40mg, 400mg, and 1200mg per kg of rat as the daily oral doses did not show any characterized sign in the weight gain rate, anatomical findings, and biochemical studies. For 3 weeks following the first week the weight gain rates of all test group were reduced to $4.2{\sim}7%$ below the weight gain rate of control. In this period serum GPT, GOT, and Alkaline phosphatase value were increased significantly indicating the symptoms of Bracken Fern poisonings. The pathological findings of all test groups for 28 days showed acute and chronic intestinal lesion and liver damage with steatosis especially in 1200g/kg rat groups. In this experiment the Bracken poisonings appeared slowly in rats of 400mg/kg and 1200mg/kg for two weeks and in rats of 40mg/kg for 3 weeks, showing the symptoms of lowering of weight gain rate, subacute hepatitis, hepatic steatosis and enteritis in 28 days experiment.

• Applied Biological Chemistry
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• v.35 no.5
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• pp.367-374
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• 1992

This study was performed to investigate effects of probable detoxifying enzyme activity and toxicity by pesticides and their combinations in the fresh water fish. Seven pesticides including IBP, isoprothiolane, cartap, ridomil, chlorothalonil, captafol and endosulfan were subjected to investigate for their acute toxicites and synergism possibilities. The $LC_{50}$ value of endosulfan was the lowest at showing 0.0079 ppm and that of metalaxyl was the highest as showing 40 ppm over. The synergism effects of relative pesticides were observed in the combinations of isoprothiolane+IBP and isoprothiolane+cartap. The changes of glycogen contents in fish liver were assayed for 5 pesticides and its highest inhibition effect of glycogen showed in IBP treated fish. The activity of probable detoxifying enzymes including carboxylesterase (CE), glutathion S-transferase (GST) and lactate dehydrogenase (LDH) were assayed in carp liver at dose of sublethal concentrations. Effects of pesticides on changes in each enzyme activities were as follows: carboxylesterase (CE) activities were the highest in IBP and gtutathion S-transferase (GST) activities were the highest in iosoprothiolane+IBP. Both activities of carboxylesterase (CE) and glutahtion S-transferase (GST) were increased by 5 chemicals. The highest LDH activity showed in isoprothiolane treated fish, while the lowest activity was observed in isoprothiolane+cartap. Sublethal exposure to cartap and isoprothiolane+cartap in carp exerted various effects on LDH activity.

• Journal of Life Science
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• v.26 no.2
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• pp.181-189
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• 2016

The aim of this study was to identify the effects of dithiopyr (DTP), a herbicide, on behavior in zebrafish. The toxicity of DTP has rarely been investigated in fish. In the present study, zebrafish were exposed to different concentrations of DTP in the range of 10-20 μM for 48 h in a test container, in order to measure the value of median lethal concentrations (LC₅₀). Behavioral experiments were performed, including the novel tank test (NTT) and the open field test (OFT), to assess stress responses or locomotion. After exposure to the DTP solution at a sublethal concentration of 2.5–10 μM for 6 min, the behavior of the zebrafish was observed for 6 min. In the acute toxicity test, the LC₅₀ value of DTP showed as 14.49 μM in the zebrafish. The NTT showed that the duration of immobility and the velocity were significantly increased by exposure at a concentration of 5 μM of DTP, compared with a control group (p<0.05). However, compared with the control group, DTP significantly decreased the distance moved and the frequency at the top of the tank, and significantly increased the turn angle and duration at the bottom, in a concentration-dependent manner (p<0.05). In addition, in the OFT, exposure to DTP significantly decreased the distance moved and velocity compared with the control group (p<0.05). Exposure to DTP also significantly increased the duration of immobility, the turn angle, and the meandering movement, in a concentration-dependent manner (p<0.05). Further, exposure to DTP at a low concentration elevated whole-body cortisol levels in the zebrafish. The results of this study thus suggest that DTP induces a toxic response and negative effects on behavior and the endocrine system in zebrafish.