• Title/Summary/Keyword: Sodium toxicity

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Use of Cultured Bioartificial Skins as in vitro Models for Cutaneous Toxicity Testing (생인공피부를 이용한 독성 반응 시험)

  • Yang, Eun-Kyung;Yoon, Hee-Hoon;Park, Jung-Keug;Park, Soo-Nam;Ko, Kang-Il;Kim, Ki-Ho
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.26 no.1
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    • pp.17-40
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    • 2000
  • Cytotoxicity assays using artificial skins have been proposed as in vitro alternatives to minimize animal ocular and dermal irritation testing. Accordingly, the responses of artificial skins to the well-characterized chemical irritants toluene, glutaraldehyde, and sodium lauryl sulfate (SLS), and the nonirritant polyethylene glycol were studied. The evaluation of the irritating and non-irritating test chemicals was also compared with the responses observed in human dermal fibroblasts and human epidermal keratinocytes grown in a monolayer culture. The responses monitored included an MTT mitochondrial functionality assay. In order to better understand the local mechanisms involved in skin damage and repair, the production of several mitogenic proinflammatory mediators, interleukin-l$\alpha$, 12-HETE, and 15-HETE, was also investigated. Dose-dependent increases in the levels of かIn and the HETEs were observed in the underlying medium of the skin systems exposed to the two skin irritants, glutaraldehyde and SLS. The results of the present study show that both human artificial skins can be used as efficient in vitro testing models for the evaluation of skin toxicity and for screening contact skin irritancy.

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Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
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    • v.23 no.4
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    • pp.405-413
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    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

Fabrication and application of cell-based microfluidic chip for eye-irritation test of chemicals (화학 물질의 안자극 시험용 세포 기반 미세유체 칩의 제작 및 응용)

  • Cho, Sujin;Rhee, Seog Woo
    • Analytical Science and Technology
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    • v.34 no.6
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    • pp.275-283
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    • 2021
  • This study presents the development of cell-based microfluidic chips for the performance of acute eye irritation tests due to chemicals and examined some of their applications. Microfluidic chips were fabricated by photolithography and soft lithography, and they had three compartments with different areas for cell culture. Rabbit corneal epithelial cells were used for the eye irritation test. The death of cells cultured inside the chip was monitored at regular time intervals after treatment with an aqueous solution of chemicals, and the cell death rate constants were calculated based on the viability curve. The performance of the microfluidic chip was verified by examining the effects of cell-cell junctions, cell-substrate adhesion, and initial cell numbers compared to cell death rates. Eye irritation tests were performed at various concentrations of an aqueous solution of sodium dodecyl sulfate (SDS), a standard substance for the eye irritant test. The cells were exposed to the SDS aqueous solution for 300 s, and the resulting eye irritation was assessed by cell viability. Finally, the equation for calculating the toxicity score (TS) was derived based on the weighting factor for each compartment in the chip. The cell-based microfluidic chip developed in this study may be used for eye irritation tests from chemicals used in cosmetics and pharmaceuticals.

Possible Protective Effects of Quercetin and Sodium Gluconate Against Colon Cancer Induction by Dimethylhydrazine in Mice

  • Saleem, TH;Attya, AM;Ahmed, EA;Ragab, SMM;Abdallah, MA Ali;Omar, HM
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5823-5828
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    • 2015
  • Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

Alleviating Effects of Nitric Oxide on Cadmium Toxicity in White Poplar (Populus alba)

  • Semsettin Kulac;Yakup Cikili;Halil Samet;Ertugrul Filiz
    • Journal of Forest and Environmental Science
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    • v.40 no.1
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    • pp.43-52
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    • 2024
  • Cadmium (Cd) is non-essential heavy metal that negatively affects plant metabolism. Nitric oxide (NO) is an increasingly important molecule for plant metabolism that makes signaling. In this study, it was aimed to investigate the alleviating effect of sodium nitroprusside (SNP) application as NO donor in white poplar (Populus alba) under Cd stress conditions. SNP and without SNP treatments increased the Cd accumulation in root tissue. While photosynthetic pigments (Chl a, Chl b, Chl a+b, and carotenoid) content decreased by only Cd application, SNP+Cd application decreased the rate of photosynthetic pigments reduction. When the results of Cd and Cd+SNP applications were evaluated for mineral (Fe, Zn, Mn and Cu) uptake, it was found that the positive effect of SNP was heterogeneously affected. Depending on SNP application, it was found that malondialdehyde (MDA) amount decreased in leaf in 100 µM Cd applications while hydrogen peroxide (H2O2) amount decreased in 100 and 500 µM Cd applications. When antioxidant enzyme activities were examined, it was found that catalase (CAT) and ascorbate peroxidase (APX) enzyme activities increased with 100 µM SNP applications under all Cd applications. As a result, it was found that SNP application under Cd stress generally supports physiological processes positively in white poplar, suggesting that NO molecule plays important alleviating roles in plant metabolism.

Effect of Gentamicin on Sodium Transport in Human Erythrocytes (Gentamicin이 적혈구막을 통한 $Na^+$ 이동에 미치는 영향)

  • Kim, Kyung-Hyo;Park, Kae-Sook;Kim, Hee-Jin;Shin, Ho-Im;An, Mi-Ra;Kang, Bok-Soon
    • The Korean Journal of Physiology
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    • v.23 no.1
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    • pp.23-34
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    • 1989
  • Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of $Na^{+}-K^{+}$ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on $Na^{+}-K^{+}$ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and $Na^{+}-K^{+}$ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of $Na^{+}-K^{+}$ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on $Na^{+}-K^{+}$ ATPase activity, actives sodium and potassium transport across red blood cell and $^{3}H-ouabain$ binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and $Na^{+}-K^{+}$ ATPase at all concentrations tested. 2) GM inhibited active $^{22}Na$ efflux across red blood cell. When ouabain is present, the rate of $^{22}Na$ efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active $^{22}Na$ efflux was more pronounced. 3) Active $^{86}Rb$ influx was inhibited significantly by GM. In the presence of ouabain, the rate of $^{86}Rb$ influx is markedly inhibited. But $^{86}Rb$ influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, $^{3}H-ouabain$ binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of $Na^{+}-K^{+}$ ATPase activity and an increase in ouabain binding to red blood cell membranes.

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A Preliminary Study on Effects of Different Dietary Selenium (Se) Levels on Growth Performance and Toxicity in Juvenile Black Seabream, Acathopagrus schlegeli (Bleeker)

  • Lee, Seunghyung;Lee, Jun-Ho;Bai, Sungchul C.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.12
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    • pp.1794-1799
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    • 2008
  • This preliminary feeding trial was conducted to study the effects of different dietary selenium (Se) levels on growth performance and toxicity in juvenile black seabream, Acanthopagrus schlegeli (Bleeker). Fish averaging $7.0{\pm}0.1g$ ($mean{\pm}SD$) were fed one of the five semi-purified diets containing 0.21, 0.30, 0.52, 1.29 and 12.3 mg sodium selenite ($Na_2SeO_3$)/kg diet (Se 0.21, Se 0.30, Se 0.52, Se 1.29 or Se 12.3) for 15 weeks. After the feeding trial, weight gain (WG), feed efficiency (FE), specific growth rate (SGR) and protein efficiency ratio (PER) of fish fed Se 0.21, Se 0.30, Se 0.52 and Se 1.29 diets were not significantly different, however fish fed Se 12.3 diet showed significantly lower WG, FE, SGR and PER than those of fish fed the other diets (p<0.05). Fish fed Se 0.21, Se 0.30, Se 0.52, Se 1.29 and Se 12.3 diets showed no significant differences in hematocrit (PCV), hemoglobin (Hb) and red blood cells (RBC), however fish fed Se 12.3 diet showed lower values of PCV, Hb and RBC than those of fish fed the other diets. Histopathological lesions such as tubular necrosis and polycystic dilation of tubules in the kidney tissues were observed in fish fed Se 12.3 diet. Se was accumulated in a dose-dependent manner in the liver, kidney, muscle and gill tissues. Based on the results of this preliminary feeding trial, a dietary Se level of 0.21 mg $Na_2SeO_3/kg$ diet could be optimal for proper growth performances, and a dietary Se level of 12.3 mg $Na_2SeO_3/kg$ diet may ultimately be toxic to juvenile black seabream, Acanthopagrus schlegeli.

Studies on the Structure and Biological Activity of Microcystins Produced from Korean Cyanobacteria, Microcystis Species (한국산 남조류 Microcystis로부터 생산된 microcystin 구조와 생물활성에 관한 연구)

  • Choi, Byoung Wook;Noh, Young Ho;Lee, Jong-Soo
    • Applied Chemistry for Engineering
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    • v.8 no.4
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    • pp.610-616
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    • 1997
  • Hepatotoxic cyanobacteria, Microcystis species, were collected from the Nakdong River and we could isolate hepatotoxins, microcystin-LR and microcystin-RR, which are also strong inhibitors of protein phosphatase 1 and 2A. From the microcystins, several microcystin derivatives were synthesized and tested on the mouse toxicity in order to establish the structure-activity relationship. Esterification od carboxyl groups of Glu and MeAsp residue produced nontoxic compounds. However, when we reduced the Mdha residue with sodium borohydride into Ala residue, toxicity was still maintained. Also, the change of guanidyl moiety of Arg residue in microcystin-LR into dimethylpyrimidyl moiety did not change the toxicity of microcystins as well. Thus the carboxyl groups seem to play important roles in binding with protein phosphatase 1 and 2A, whereas Mdha residue and the guanidyl moiety of Arg residue do not.

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Protective effect of selenium on alcohol and/or paraquat-induced thyroid toxicity in guinea pigs (Guinea pig에서 alcohol과 paraquat에 의한 갑상선 독성에 미치는 selenium의 방어 효과)

  • Kim, Jin-sang;Kang, Hyung-sub
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.209-219
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    • 1996
  • This study examined the effect of alcohol(AL) and/or paraquat(PQ) on serum TSH, thyroid hormones and enzyme activities, and the protective effect of selenium(SE) againse alcohol and/or paraquat-induced thyroid toxicity in guinea pigs. The experomental group consisted of control, 15% alcohol(AL), 4ppm sodium selentite(SE), 200ppm paraquat(PQ), AL+PQ, AL+SE, PQ+SE and AL+PQ+SE mixed in drinking water-fed guinea pigs for 4 weeks. The morphological changes of thyroid gland were studies on paraffin-embedded sections stained with H-E stain. Body weight losses, high serum concentration in TSH and cholesterol, and low values on triiodothyronine($T_3$), thyrozine($T_4$), free $T_4$ and alkaline phosophatase(ALP) were produced in the groups fed AL and/or PQ. We also noted that AL+PQ-fed group was marked increase in serum TSH. In AL or AL+PQ-fed groups when cpmpared to control group had increased the ratio of thyroid weight to body weight(ratio Twt/Bwt), whereas the ratio Twt/Bwt was decresed in SE or PQ-fed groups. However, the serum TSH, $T_3$,$T_4$ free $T_4$ and cholesterol values, and the ratio Twt/Bwt were reversed in groups given the combination of SE, compared with AL and/or Pq-fed groups, also ALP values were reversed in groups given the combination of SE, compared with AL or AL+PQ-fed groups. In microscope, morphological changes showed a remarkable between the AL or PQ-fed group and controls. In AL+PQ+SE-fed guinca pig, follicular colloid is high density in thyroid follicle and increased in connective tissue around the thyroid cells, and thyroidal epithelia were composed of cuboidal or columnar epithelium. The indicated that the morphological changes of thyroid were direct action in the thyroid cell. The results of this study confirmed that the toxic effect of AL or PQ on thyroid occur independently of changes in liver function, and that SE confers marked protection against AL or PQ-induced thyroid toxicity.

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Four-Week Repeated Oral Toxicity Study of Clean Natural in Sprague-Dawley Rats (Clean Natural의 Sprague-Dawley 랫드를 이용한 4주 반복경구투여 독성시험)

  • Kim, Eui-Kyung;Kim, Jun-Young;Lee, Hu-Jang
    • Toxicological Research
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    • v.21 no.3
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    • pp.263-269
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    • 2005
  • This study was performed to investigate repeated-dose toxicities of Clean natural, a new disinfectant, in Sprague-Dawley(SD) rats. In the 4-week repeated oral toxicity study, Clean Natural was orally administered once daily via gavage to male and female rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg body weight for 4-weeks. There were no deaths and clinical signs during the dosing period. In both sexes, there were no statistically significant differences between the administered and control groups in urinalysis indicators and hematological parameters. In serum biochemistry, aspartate aminotransferase(AST) was significantly decreased and sodium content was increased in the 2,000 mg/kg male group, while chlorine was significantly decreased in the 2,000 mg/kg female group. Also, albumin, total cholesterol and total bilirubin were significantly increased in the 2,000 mg/kg male and female group. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver was observed in the 2,000 mg/kg male and female groups. And pigmentation in the spleen was observed in the 2,000 mg/kg male group. In conclusion, four-week repeated oral dose of Clean Natural to rats did not cause apparent toxicological change at the dose less than 2,000 mg/kg body weight. Thus it is suggested that no-observed adverse-effect level(NOAEL) for Clean Natural in rats was considered to be 1,000 mg/kg/day.