• Toxicological Research
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• v.3 no.1
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• pp.15-26
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• 1987

The mutagenicity of pranoprofen, a new antiinflammatory agent primarily used in Japan, was evaluated by employing several different methods such as the Ames test, micronucleus test, and the sister chromatid exchange test. For the Ames test, various doses of pranoprofen (5 and 1 mg, 100, 10, and 1 ${\mu}$g per plate) were applied, with or without the mammalian liver S-9 fraction, to the S. typhimurium LT2. For the micronucleus test, 24 hours after administering the various doses of pranoprofen (200, 100, and 50 mg/kg) to male mice by aral intubation, the femura of each group were isolated and the bone marrow samples were prepared. The micronucleated red cells and the ratio of the polychromatic versus the normochroomatic cells were counted. For the sister chromatid exchange test, the maximal non-cytotoxic concentrations (10 to 0.1 mM pranoprofen) were applied to the culture media of the Chinese Hamster Ovary (CHO) cells for 24 hrs. The numbers of revertant colonies did not increase with the increasing doses of pranoprofen when teseted with various strains of S. typhimurium. In the micronucleus test employing mice, the pranoprofen was identkfied to be a non-clastogen and a non-spindle poison. In the sister chromatid exchange test employing the cultured CHO cells, the pranoprofen did not increase the incidences of chromosomal abnormality. Based on these results, pranoprofen was found to have no mutagenic activity.

• Toxicological Research
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• v.26 no.3
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• pp.203-208
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• 2010

Bronchoalveolar lavage (BAL) is a useful tool in researches and in clinical medicine of lung diseases because the BAL fluid contains biochemical and cytological indicators of the cellular response to infection, drugs, or toxicants. However, the variability among laboratories regarding the technique and the processing of the BAL material limits clinical research. The aim of this study was to determine the suction frequency and lavage fraction number necessary to reduce the variability in lavage using male Sprague-Dawley rats. We compared the total cell number and protein level of each lavage fraction and concluded that more cells and protein can be obtained by repetitive lavage with a suction frequency of 2 or 3 than by lavage with a single suction. On the basis of total cell recovery, approximately 70% of cells were obtained from fractions 1~3. The first lavage fraction should be used for evaluation of protein concentration because fractions 2~5 of lavage fluid were diluted in manifolds. These observations were confirmed in bleomycin-induced inflamed lungs of rats. We further compared the BAL data from the whole lobes with data from the right lobes and concluded that BAL data of the right lobes represented data of the whole lobes. However, this conclusion can only be applied to general lung diseases. At the end, this study provides an insight into the technical or analytical problems of lavage study in vivo.

• Toxicological Research
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• v.25 no.4
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• pp.243-251
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• 2009

Present study was conducted to evaluate the anti oxidative activity of the Agrimonia pilosa-Ledeb leaves on non-lipid oxidative damage. The antioxidative activity of methanolic (MeOH) extract of the Agrimonia pilosa-Ledeb leaves on non-lipid oxidation, including liposome oxidation, deoxyribose oxidation, protein oxidation, chelating activity against metal ions, scavenging activity against hydrogen peroxide, scavenging activity against hydroxyl radical and 2'-deoxyguanosine (2'-dG) oxidation were investigated. The MeOH extract of the Agrimonia pilosa-Ledeb leaves exhibited high anti oxidative activity in the liposome model system. Deoxyribose peroxidation was inhibited by the MeOH extract of the Agrimonia pilosa-Ledeb leaves and MeOH extract of the Agrimonia pilosa-Ledeb leaves provided remarkable protection against damage to deoxyribose. Protective effect of MeOH extracts of the Agrimonia pilosa-Ledeb leaves on protein damage was observed at $600{\mu}g$ level (82.05%). The MeOH extracts of the Agrimonia pilosa-Ledeb leaves at $300{\mu}g$ revealed metal binding ability (32.64%) for hydrogen peroxide. Furthermore, the oxidation of 2'-deoxyguanosine (2'-dG) to 8-hydroxy-2-deoxyguanosine (8-OH-2'dG) was inhibited by MeOH extracts of the Agrimonia pilosa-Ledeb leaves and scavenging activity for hydroxyl radical exhibited a remarkable effect. From the results in the present study on biological model systems, we concluded that MeOH extract of the Agrimonia pilosa-Ledeb leaves was effective in the protection of non-lipids against various oxidative model systems.

• Toxicological Research
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• v.23 no.2
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• pp.165-172
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• 2007

Glycyrrhizae Radix, the dried roots of Glycyrrhiza glabra or Glycyrrhiza uralensis Fischer(Legumino-sae), has been used as a medicine for treatment of imflammation, arthritis, respiratory ailment, skin diseases and liver problems. The purpose of this study was to examine the effect of 70% ethanol extract, 18-${\beta}$-glycyrrhetinic acid, glycyrol and carbenoxolone disodium from Glycyrrhizae Radix on gastritis and gastric cancer. Using these materials, we tested antibacterial activity against Helicobacter pylori, antigastritic activity for HCI-ethanol-induced gastric lesion and the pylorus ligated gastric secretion with rats, and cell viability in gastric cancer cell. 18-${\beta}$-glycyrrhetinic acid and carbenoxolone disodium decreased the volume of gastric secretion and acid output in pylorus ligated rats. Also, carbenoxolone disodium had a strong effect of antibacterial activity on H. pylori. In addition 18-${\beta}$-glycyrrhetinic acid and glycyrol reduced cell viability in human gastric cancer cells(AGS and SNU638 cell) in dose-dependent manner. The reduction of total acid output and gastric secretion as well as the anti-bacterial activity against H. pylori might account for the antigastritic effects of carbenoxolone disodium.

• Toxicological Research
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• v.34 no.2
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• Toxicological Research
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• v.34 no.2
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• pp.85-95
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• 2018

The term Butterfly tea refers to decoction of Mariposa christia vespertilionis leaves which is widely consumed by cancer patients throughout Malaysia and has gained a huge popularity among Malaysians, not only cancer patients but also researchers to discover the real potential of this plant. Herein, the study is aimed at evaluating the possible toxicity in 28-day subacute oral toxicity of ethanolic extract M. christia vespertilionis in male Sprague Dawley rats. The 28-day subacute toxicity study was conducted to detect the no-observed adverse effect level (NOAEL). In this study, a total of 30 rats were divided into the control, 5% DMSO (vehicle), low dose (75 mg/kg), medium dose (125 mg/kg) and high dose (250 mg/kg) groups. The extract was administered daily from day 1 until day 28. At the end of the study, the animals were humanely sacrificed and assessed for the effect extract of Mariposa christia vespertilionis leaves on body weight and relative organ weights and haematological, biochemical and histopathological parameters. The haematological and serum biochemical parameters for the assessment of kidney and liver injuries were carried out. Results of haematological and serum biochemistry results showed no changes in the control and treated groups. In the histopathology, evaluation of kidney tissues in all treated groups showed no significant (p > 0.05) lesions. In contrast to kidney, liver tissues showed significant differences (p < 0.05) in lesions observed in low dose (430 mg), medium dose (700 mg) and high dose (1480 mg) groups with very mild, mild and mild to moderate lesion of hepatic necrosis, in the respective groups, and very mild hepatic degeneration and hepatitis were scored in all three groups.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1310-1316
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• 2005

To evaluate the toxicological properties of human cytochrome P450 2E1 (CYP2E1) induced by ethanol and possible protective effects of various green tea catechins on alcohol-induced toxicity, transfected HepG2 cells that stably and constitutively express human CYP2E1 were established using the recombinant retroviral expression vector. Exposure of the CYP2E1-expressing HepG2 cells to high concentration of ethanol (200 mM) for 5 days resulted in a more than $50\%$ increase of cytotoxicity, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) production, and loss of normal morphology, in comparison with HepG2 cells containing control vector. Treatment of the cells with various catechins increased cell viability by more than 2-fold. (-)-Epicatechin gallate and(-)-catechin gallate at the lowest concentration ($5\;{\mu}M$) attenuated cell death induced CYP2E1 by $60-65\%$. Therefore, the results showed that the catechins, including epimerized catechins, have strong protective effects against alcohol-induced CYP2E1 toxicity, and it is correlated with antioxidant effect.

• Environmental Analysis Health and Toxicology
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• v.25 no.2
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• pp.131-143
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• 2010

We performed the tests of acute and subchronic inhalation toxicity of methyl formate, which has limited toxicological data in spite of its widespread use and enhanced hazard consequent on its high volatility. The median lethal concentration ($LC_{50}$) was evaluated to be above 5,000ppm(12.27 mg/L). In the test with subchronic inhalation, there are no deaths, but with reduction of body weight, food intake, organ weight by exposure to 400 (0.98 mg/L) and 1,600 (3.92 mg/L) ppm, dose-dependently. There were statistical differences in some hematological and blood biochemical parameters as compared to control (e.g. neutrophile and lymphocyte in the 1,600 ppm group, calcium and A/G in 1,600 ppm group). Methyl formate under the exposure of 1,600 ppm showed the respiratory findings with nasal, it was confirmed that the chemical has respiratory hazard with 1,600 ppm inhalation exposure, induces nasal epithelial atrophy, olfactory cell degeneration/regeneration and the contraction of olfactory cells, etc. According to the notification with Ministry of Labor (No. 2009-68) for classification, labeling and MSDS of chemicals, it is suggested for methyl formate to be classified as category 4 in acute (10.0$4\leq20.0$ mg/L), category 2 (0.2$\leq$1.0 mg/L/6h, 90 days) in specific target organ-repeated exposure.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.470-477
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• 1995

Flavonoids from Scutellariae Radix possessed a dual function both as an anti-inflammatory agent and an enhancer of cellular activity in gingival fibroblast. The purpose of this study was to evaluate on the toxicity of ethanolic extract from the root of Scutellariae Radix Georgi and its flavonoids, Wogonin, Baicalein, and Baicalin were isolated and purified by the following method. The crude drug was extracted with ethyl acetate and the residue was dissolved in ethyl alcohol. The ethyl alcohol soluble fraction was separated, concentrated, and then chromatographed on a silica gel column. The acute oral LD 50 in rats was determined for EtOH ex. of Scutellariae Radix and three compounds were evaluated with a single oral gavage at three graded dosage levels. The acute intravenous LD 50 was determined with a single intravenous injection via the jugular vein at three graded dosage levels. Groups of 5 male and 5 female rats, 6 week of age at the start of the study, were fed diets containing 3 graded dosage levels for 14 days. Groups of 5 male and 5 female hamster received O.5ml of the test article at once in a day for 5 days to the buccal cheek pouch for two minutes each. The acute oral LD50 for EtOH ex. of Scutellariae Radix is 1430mg/kg, and for Wogonin 1320mg/kg, for Baicalein 1250mg/kg, for Baicalin 1330mg/kg. The acute intravenous toxicity of EtOH ex. of Scutellariae Radix and its extracts was found to be 27mg/kg body weight No toxic effects were observed in rats fed up to 200mg/kg of EtOH ex. of Scutellariae Radix, Wogonin, Baicalein and Baicalin in the diet for 14 days. The acute Mucouse Membrane LD 50 in hamsters was found to be greater than 100mg/kg. These results suggested that EtOH ex. of Scutellariae Radix and its flavonoids are safe for oral care products using limited amount of extract.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.18-24
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• 2011

Objective: Leejung-tang (Rechu-to in Japanese) is a traditional Korean herbal formula used for treatment of gastrointestinal disorders such as vomiting, stomach pain, chronic gastritis and gastrointestinal ulceration. The present study was carried out to investigate the potential acute toxicity of Leejung-tang water extract (LJT) by a single oral dose in Crl:CD (SD) rats in compliance with current guidelines. Methods: In the preliminary study, there were no adverse effects such as death, clinical signs, and body weight changes at dose levels of 500, 1000, and 2000 mg/kg/day body weight. Based on the results, a dose of 2000 mg/kg was selected as the toxicological limited dose. LJT was administered once by gavage to male and female rats at dose levels of 0 and 2000 mg/kg bodyweight. During the study period, mortalities, clinical findings, and body weight changes were observed for 14 days following the administration. On day 14 after the treatment, the animals were sacrificed by carbon dioxide overdose and complete gross postmortem examinations were performed. Results: In present study, no treatment-related deaths were observed. There were no adverse effects on clinical signs and body weight changes. In addition, there were no observed gross findings in all groups except for a kidney cyst in the 2000 mg/kg/day female group. Conclusion: The results indicated that LJT did not induce toxic effects at a dose level up to 2000 mg/kg in rats and its median lethal dose ($LD_{50}$) was considered to be over 2000 mg/kg/day body weight for both genders.