• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.89-94
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• 2003

Tributyltin (TBT) used world-wide in antifouling paints for ships is a widespread environmental pollutant and cause reproductive organs atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. In this study, we investigated that the mechanisms underlying DNA fragmentation induced by TBT in the rat leyding cell line, R2C. Effects of TBT on intracellular Ca$\^$2+/ level and reactive oxygen species (ROS) were investigated in R2C cells by fluorescence detector. TBT significantly induced intracellular Ca$\^$2+/ level in a time-dependent manner. The rise in intracellular Ca$\^$2+/ level was followed by a time-dependent generation of reactive oxygen species (ROS) at the cytosol level. Simultaneously, TBT induced the release of cytochrome c from the mitochondrial membrane into the cytosol. Furthermore, ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca$\^$2+/ chelator, indicating the important role of Ca$\^$2+/ in R2C during these early intracellular events. In addition, Z-DEVD FMK, a caspase-3 inhibitor, decreased apoptosis by TBT. Taken together, the present results indicated that the apoptotic pathway by TBT might start with an increase in intracellular Ca$\^$2+/ level, continues with release of ROS and cytochrome c from mitochondria, activation of caspases,and finally results in DNA fragmentation.

• Korean Journal of Ecology and Environment
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• v.36 no.1 s.102
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• pp.83-94
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• 2003

Concentrated releases of zinc into water usually results from discharges associated with industrial purpose. The released zinc into soil is corroded and released into water. In aquatic environment, exess zinc is toxic to the organisms and causes the growth inhibition and malformation of them as a heavy metal. In this study, excess zinc toxicity was tested by FETAX (frog embryo teratogenetic assay with Xenopus)as in vivo system. Xenopus embryos at st.9 were exposed to $100{\sim}900\;{\mu}M$ of zinc for 7 days and 81% of individuals were survived in 100 ${\mu}M$, and 25% were survived in 1000M of zinc solution. In external malformations, swelled belly and intestinal dysplasia were common, and all of tested individuals showed these malformations in 200 ${\mu}M$ or higher concentration of zinc. In 400 ${\mu}M$ or higher concentration, all of tested tadpoles showed faded heart. Also, hypo-pigmentation, lens hernia and loose digestive track were very frequently found in 100 ${\mu}M$ of zinc. The histological study with paraffin section of zinc treated tadpoles showed following abnormalities; regeneration of photoreceptor on retina, reduced vitreous chamber in eye, reduction of red blood cells in heart, abnormal liver, swelling of pronephric cell, muscle dysplasia and palatal papilloma. These abnormalities may be caused by the degeneration of mitochondria, inhibition of cell adhesion, and the formation of leghemoglobin by zinc due to the substitution of $Ca^{2+}$ by $Zn^{2+}$. The body length was reduced due to the excess zinc. From a statistical result, body lengths of 300 ${\mu}M$ or higher concentrative g개ups was significantly reduced comparing that of control group. Recently, many spontaneous malformations and reduction of amphibians are reported, From the results of present study, excess zinc mi호t be a factor of amphibian reduction, and the control of zinc discharges is very important.

• The Korean Journal of Malacology
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• v.24 no.3
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• pp.229-241
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• 2008

Changes of growth and histopathological feature in the mantle structure of the equilateral venus, Gomphina veneriformis exposed to tribultyltin chloride (TBTCl) for 36 weeks were observed. Concentrations of TBTCl were 0, 0.4, 0.6, and $0.8{\mu}g/L$. A regression analysis by power function of SPSS was shown that the growth of experimental groups was significantly decreased after 12 weeks of exposure. For histological analysis, mantle tissues were characterized using H-E stain, AB-PAS (pH 2.5) reaction and Masson's trichrome stain, and epidermal layer thickness and mucous cell distribution were analysed using the image analyser. The mantle had 4-folds (inner-inner, inner-outer, middle, and outer) and its epidermal layer consisted of simple epithlia. A periostracum was observed in the periostracal groove between middle and outer fold. Inner epidermal layer consisted of simple ciliated columnar epithelia, but the outer epidermal layer consisted of simple non-ciliated columnar epithelia. Alcian blue positive mucous cells showed blue color (7462c, 653c) in the inner fold, violet color (2583c) in the middle fold, and blue color (647c, 7455c) in inner epidermal layer (numbers in the parenthesis are codes of Pantone process coated color). Hemolymph sinus in the mantle was extended, and mucous cells in inner plica of the middle fold were stained as blue (7455c) and violet (2587c), after 12 weeks of TBTCI exposure. Cilia and striated border were disappeared, and number of mucous cells in the inner epidermal layer was reduced. Serious histopathological changes in middle and outer fold near the periostracum were observed after 36 weeks. Moreover, epidermal layer thickness and mucous cell distribution were showed decreasing tendency as exposure time to TBTCI was increased. Results of this study suggested that TBTCl induced growth disorder with histopathological changes.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.281-290
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• 1996

Purpose : Chest irradiation leads to a significant cardiac injury in a number of patients. To prevent, or to reduce the risk of radiation-induced cardiac injury, pentoxifylline(PTX), a haemorrheologic agent that improves the blood flow through small blood capillaries has been employed. Materials and Methods : One hundred and eighty ICR mice were divided into three study groups: control, radiation alone, and radiation-pentoxifylline. Each group was subdivided into 12 subgroups: 1 3, 6 and 10 days and 2, 3, 4, 6, 8, 12, 16 and 20 weeks by observation Period after irradiation. The total 15Gy of radiation was delivered in a single fraction through anterior mediastinal port. Pentoxifylline was injected subcutaneously daily 50mg/kg to the back of the mice from the first day of irradiation throughout the observation period. The mice of each group after a certain observation period were sacrificed and sectioned for histopathologic examination of the heart. Result : The findings of acute radiation-induced carditis i.e., heterophilic infiltration and vacuolization and ballooning of endothelial cells were observed upto 6 weeks and reduced sharply afterwards. The late radiation effects including pericarditis with mononuclear cell infiltration, pericardial fibrosis, endothelial cell changes, myocardial degeneration and fibrosis present from 4 weeks onwards after irradiation but with various degree of severity. The overall process of pathologic changes of radiation-pentoxifylline group was similar to those of radiation alone group but the duration of acute stage was relatively short and the severity of late cardiac toxicity was much lesser compared with those of radiation alone group. Conclusion : Pentoxifylline can effectively reduce the late radiation-induced cardiac injury and reslve the acute effects relatively rapidly.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.1-10
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• 2004

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.205-210
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• 2010

Purpose: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Materials and Methods: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. Results: The median follow-up time was 62 months (2~202 months). The 5-year overall survival, loco regional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). Conclusion: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.215-219
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• 1991

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991, Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGy following 3 cycles of induction MVP (Mitomycin C 6 mg/$m^2$, Vinblastine 6 mg/$m^2$, Cisplatin 60 mg/$m^2$) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 46 were analyzed for this preliminary report. The response rate of induction chemotherapy was $62.5\%$ : partial response, $50\%$ and minimal response, $12.5\%$. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue.

• Food Science and Preservation
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• v.24 no.3
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• pp.431-439
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• 2017

This study was conducted to examine the antioxidant activities and physiological activities of mixture extracts (Liriope platyphylla, Schizandra chinensis and Panax ginseng C.A. Meyer) with different extraction mixing ratios (MEC, 2:1:1; ME1, 1:2:1; ME2, 1:1:2; ME3, 1.34:1.33:1.33). The yield of extracts ranged from 25.33 to 33.87%. The total polyphenol and total flavonoid contents of ME1 extracts were 1.01 g/100 g, 0.07 g/100 g, respectively. The total sugar contents of MEC extract was 22.83 g/100 g, respectively. The DPPH and ABTS radical scavenging activities of ME1 extracts at $1,000{\mu}g/mL$ were 26.79% and 21.08%. The superoxide radical scavenging and ferric-reducing antioxidant power of ME1 extracts at $1,000{\mu}g/mL$ were 67.83% and $295.47{\mu}M$, respectively. The functionalities of extracts were investigated with L-132 and RAW264.7 cell lines. The extracts on different mixing ratios did not show the toxicity on L-132 and RAW264.7 cell line in $100-2,500{\mu}g/mL$. The ME1 extract of $1,000{\mu}g/mL$ performed better than other extracts protective effects against oxidative stess in L-132 cells (81.22%) and the ME2 extract at $1,000{\mu}g/mL$ decreased nitric oxide production by $7.48{\mu}M$ which was more potent than other extracts. There results suggest that the ME1 extracts may be a useful functional food material in the food industry.

• Journal of Life Science
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• v.31 no.3
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• pp.305-313
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• 2021

This study verified the antioxidant and whitening activities of a Pinus koraiensis extract (PK) and a Hibiscus cannabinus L. extract (HC), and further evaluated the interaction of the extract ingredients when mixed at a 1:1 ratio (PKHC). The electron-donating and ABTS+ radical scavenging activities of the PKHC extract at 1,000 ㎍/ml concentration were 93.7% and 94%, respectively, indicating a higher efficacy than achieved with either extract alone. Measurements of the tyrosinase the activities in response to PK, HC, and PKHC extracts at 1,000 ㎍/ml concentrations showed inhibitions of 40%, 27.5%, and 43%, respectively, confirming a higher efficacy of the mixture due to the synergistic action of the ingredients. The cell toxicity values in melanoma cells treated with PK, HC, and PKHC at 1,000 ㎍/ml concentration were 87.4%, 80.2%, and 98%, confirming a higher viability in cells treated with the mixture due to antagonism. The expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and tyrosinase protein expression determined by Western blotting decreased by 53.9%, 64.8%, 67.3%, and 56.1%, respectively, when PKHC was administered at a concentration of 100 ㎍/ml. Reverse transcription-polymerase chain reaction (RT- PCR) results also showed that PKHC at a concentration of 100 ㎍/ml inhibited the mRNA expression of MITF, TRP-1, TRP-2, and tyrosinase mRNA by 54.4%, 64.9%, 66.6%, and 63.1%, respectively. Taken together, the data confirmed the antioxidant and whitening effect of the PKHC extract and verified the possibility that this extract mixture has great potential as a cosmetic ingredient.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.1
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• pp.87-96
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• 2023

This study was conducted to discover substances that regulate skin surface acidification using human epidermal keratinocyte cell lines, and to investigate their effects on the moisturizing ability and skin barrier function of the stratum corneum. Prunella vulgaris (P. vulgaris) is an herb widely distributed in Northwest Africa and North America that has been studied for its anti-apoptotic, antioxidant, and anti-inflammatory effects. However, research on the regulation of NHE1 expression and the restoration of skin barrier function has not been conducted. Analysis of P. vulgaris revealed the presence of rosmarinic acid and caffeic acid as active ingredients, which were tested for toxicity in human epidermal keratinocyte cell lines (HaCaT), and showed no toxic effects were observed at high concentarion (100 ㎍/mL or 100 µM). It is known that sodium-hydrogen ion exchange pumps (NHE1) decrease in expression in aging skin to maintain the acidic pH of the stratum corneum, and it is hypothesized that this decrease plays an important role in the impaired restoration of skin barrier function in aging skin. P. vulgaris extract and caffeic acid increased the expression of NHE1 in keratinocytes, increased the expression of natural moisturizing factor (NMF) precursor filaggrin and ceramide synthesis enzyme serine palmitoyl transferase (SPT). In addition, P. vulgaris and caffeic acid decreased the extracellular pH of keratinocytes, indicating a direct effect on skin pH regulation. Taken together, these results suggest that P. vulgaris and caffeic acid can regulate skin pH through NHE1 modulation, and may help to restore skin barrier function by increasing NMF and ceramide synthesis. These results show the possibility that honeysuckle and caffeic acid can have a positive effect on skin health, and can be the basis for the development of new skin protection products using them.