• Toxicological Research
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• v.13 no.3
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• pp.229-235
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• 1997

The elevation of intracellular calcium in various tissues due to oxidative stress induced by either menadione or adriamycin has been well documented. The increase of calcium level in platelets results in aggregation of platelets. To test the hypothesis that chemically induced calcium elevations can play a role in platelet aggregation, we have studied the effects of menadione and adriamycin on aggregation of platelets isolated from female rats. Treatment with menadione and adriamycin to platelet rich plasma (PRP) appeared to induce platelet aggregations up to 60%, as determined by aggregometry. However, exposure of PRP to rnenadione or adriamycin led to a loss of viability, as measured by lactate dehydrogenase (LDH) leakage. Morphological studies of platelets revealed that, when PRP was treated with menadione, aggregates of platelets were not observed and the numbers of platelets were decreased significantly. This suggests that menadione and adriamycin decreased turbidity by inducing platelet lysis rather than platelet aggregation. These cellular toxicities induced by menadione or adriamycin was not correlated with oxygen consumption rate but with depletion of protein thiols, suggesting that protein thiols might play an important role in chemical-induced platelet toxicity.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.207-215
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• 2009

Despite wide therapeutic use of CpG ODN against infection, allergy and cancer, the safety and toxicity of CpG ODNs were poorly delineated. Thus, we investigated whether optimal dosing of CpG ODN would affect immunotoxicological parameters in NZB/NZW F1 mice. Comparisons were made among control, non-CpG ODN and mouse CpG ODN ($10{\mu}g$)-treated groups for 4 weeks. To gauge the immunotoxicity of CpG ODNs, we measured nonspecific parameters, degree of lupus nephritis, proteinuria, or autoantibody, and cytokine expression in mRNA level of lymphocytes. We found that there were no significant differences among groups in nonspecific immunotoxicological profiles and in evaluation profiles of glomerulonephritis. However, titer of anti-dsDNA and anti-cardiolipin antibodies in mouse CpG ODN group rose three or eight-fold higher than in control group. Collectively, CpG ODN might be clinically less immunotoxic in terms of clinical profiles in lupus-prone NZB/NZW F1 mice, in spite of high autoantibody titer in CpG ODN treated groups.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.242-244
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• 1995

In vitro cell culture system has been proposed as a promising alternative model to in vivo skin irritation test. These studies were performed to screen the cytotoxicity effects of surfactants using normal human skin fibroblasts. Cell membrane integrity assessed by the leakage of lactate dehydrogenase (LDH) and mitochondrial integrity by MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromides reduction test were affected in a dose dependent manner. The irritation potential of surfactants to human skin patch test, and the changes of capillary permeability by rabbit intradermal safety test were assessed as in vivo methods. Our results suggest that LDH leakage assay and MTT reduction test using cultured human fibroblasts could be predictive for the irritancy of various surfactants in human, and LDH assay is superior correlated with in vivo test (r=0.886) to MTT test with in vivotest (r=0.757).

• Animal cells and systems
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• v.16 no.1
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• The Korean Journal of Physiology
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• v.19 no.2
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• pp.155-160
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• 1985

Dantrolene sodium(DS) is a long acting skeletal muscle relaxant which has been successfully used to control muscle spasticity in patients with various neurological disorders. However, its use is associated with hepatotoxicity. Tissue sulfhydryl group has many important roles for cellular integration and glutathione serves as a substrate for the detoxification metabolism. The purpose of this study were to investigate the effect of DS on tissue sulfhydrl group and glutathione content. Foully albino rats were divided into two groups ; saline treated (control) and DS treated groups. DS dissolved in saline was administered orally. All rats were sacrificed after 7. 14. 21 and 28 days of DS ana saline treatment by dacapitation ana liver was removed for the enzyme preparation. Total and nonprotein sulfhydryl were measured by the method of Sedlak and Lindsay (1968). Total glutathione content was assayed according to the method described by Tietze (1969) and glutathione reductase was assayed according to the method of Racker (1955), The results obtained are summarized as follows : DS administration significantly depressed the total, protein and nonprotein sulfhydryl content in liver. There were significant reduction of both total glutathione content and glutathione reductase activity in liver. On the basis of the above results it may be speculated that the toxicity of DS are well correlated with tissue sulfhydryl content and glutathione reductase activity.

• Journal of Environmental Health Sciences
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• v.19 no.4
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• pp.59-66
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• 1993

The cellular toxicity and antitumor effects of bleomycin are thought to be occurred by formation of O$_2$-Fe$^{2+}$-bleomycin complexes that degrade DNA and release O$_2^-$ and $^{\cdot}$OH radicals. Hydroxyl radicals derived from hydrogen peroxide seem most likely to be involved in the various stages of carcinogenesis, and transition metals such as iron play a central role in activation of bleomycin and in formation of hydroxyl radicals. This study was performed to investigate whether treatment with ferrous sulfate increase chromosome aberration induced by bleomycin and hydrogen peroxide, and whether there is different repair mechanism for DNA damage induced by those chemicals. Treatment with 3AB, Ara C, during G$_1$ and post-treatment with caffeine, and Hu during G$_2$ increased the frequency of chromosome aberration induced by bleomycin but post-treatment with caffeine only did function that way when hydrogen peroxide was treated. When 6.6X 10$^{-7}$ M of bleomycin or 5.0X10$^{-5}$M of hydrogen peroxide were treated simultaneously with iron, the frequency of chromosome aberration was reduced, if compared with the results by bleomycin or hydrogen per oxide alone.

• Journal of Microbiology and Biotechnology
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• v.12 no.2
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• pp.235-241
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• 2002

Sophorolipid, a biosurfactant produced from Candida bombicola ATCC 22214, showed antimicrobial activity against Bacillus subtilis, Staphylococcus xylosus, Streptococcus mutans, and Propionibacterium acne at 4, 1, 1, 0.5 ppm, respectively. Also, 100 ppm of sophorolipid inhibited $50\%$ of cell growth of plant pathogenic fungus, Botrytis cineria. However, sophorolipid showed no effect on Escherichia coli, indicating that its selective antimicrobial activity depended on the cell wall structure. Treatment of B. subtilis with sophorolipid increased leakage of intracellular enzyme, malate dehydrogenase, indicating a possible interaction of sophorolipid with a cellular membrane. Comparing lactone-type and acid-type sophorolipids, the former showed a higher antimicrobial activity. Supplementing other surfactants showed no significant effects on the antimicrobial activity. Animal study showed that 5 g of sophorolipid per kg body weight by oral administration caused no toxicity, and sophorolipid induced no irritation on the skin. These results show potential use of sophorolipid as an active ingredient in healthcare products.

• Journal of Microbiology and Biotechnology
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• v.21 no.11
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• pp.1184-1192
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• 2011

A bacterial isolate (strain JS-2) characterized as Bacillus sp. was challenged with high concentrations of toxic selenite ions. The microbe was found to transform the toxic, soluble, colorless selenite (${SeO_3}^{2-}$) oxyions to nontoxic, insoluble, red elemental selenium ($Se^0$). This process of biotransformation was accompanied by cytoplasmic and surface accumulation of electron dense selenium ($Se^0$) granules, as revealed in electron micrographs. The cells grown in the presence of selenite oxyions secreted large quantities of extracellular polymeric substances (EPS). There were quantitative and qualitative differences in the cell wall fatty acids of the culture grown in the presence of selenite ions. The relative percentage of total saturated fatty acid and cyclic fatty acid increased significantly, whereas the amount of total unsaturated fatty acids decreased when the cells were exposed to selenite stress. All these physiological adaptive responses evidently indicate a potentially important role of cell wall fatty acids and extracellular polymeric substances in determining bacterial adaptation towards selenite-induced toxicity, which thereby explains the remarkable competitiveness and ability of this microbe to survive the environmental stress.

• Journal of Korean Society on Water Environment
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• v.18 no.2
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• pp.189-199
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• 2002

Nitrogen, in its various forms, can deplete dissolved oxygen levels in receiving waters, stimulate aquatic growth, exhibit toxicity toward aquatic life and affect the suitability of sewage for reuse. Pilot-scale Rotating Biological Contactor(RBC) experiments were conducted to examine biological nitrification, respectively, of municipal sewage with five different internal recirculation ratios of 0, 1, 2, 3, and 4 using the constant hydraulic loading of $205L/m^2{\cdot}day$. The use of internal recirculation improved nitrification on account of the dilution of biodegradable organic carbon in influent sewage down to 15 mg/L of $SBOD_5$ or less. Ammonium nitrogen of $14.3{\pm}2.4%$ was consumed by cellular assimilation without the occurrence of denitrification. The thickness of biofilm didn't seem effect significantly the nitrification and denitrification. Nitrification with internal recirculation was found to occur using hydraulic loading rate of as high as $205L/m^2{\cdot}day$, which was beyond the generally known values of it.

• Toxicological Research
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• v.14 no.4
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• pp.577-585
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• 1998

Cadmium is an important industrial and environmental pollutant and has adverse effects on cell growth and metabolism, although the mechanisms of its cellular toxicity are still unclear. This study was performed to elucidate the cytotoxic mechanism of cadmium in the viewpoint of oxidative stress and cytoskeleton alterations in WB-F344 rat liver epithelial cells. 200 $\mu\textrm{M}$ $CdCl_2$ caused a severe disassembling of microtubule and micro filament and an apparent cell retraction under an observation with fluorescence micoscope. (equation omitted)-tubulin and F-actin protein were highly thiolated at 20 min and then disappeared from 1 hour after the treatment of 200 $\mu$M CdCl$_2$in the immunoblot analysis. Intracellular GSH was decreased from 1hr to 24 hrs by 66.6 or 200 $\mu\textrm{M}$ of $CdCl_2$. Intracellular protein thiol was also decreased by 22.2, 66.6 and 200 $\mu\textrm{M}$ of $CdCl_2$ at 1 hour after its treatment. The product of lipid peroxidation (malondialdehyde) was increased from 4 hrs by 66.6 and 200$\mu\textrm{M}$ of $CdCl_2$. These data indicate that cadmium induces oxidative stress involving disassembling of microtubule and micro filament, thiolation of (equation omitted)-tubulin and actin protein, depletion of GSH and protein thiol, and increase of lipid peroxidation.