• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.162-169
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• 2022

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.

• Journal of radiological science and technology
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• v.38 no.2
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• pp.107-114
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• 2015

The purpose is reducing radiation dose while maintaining of image quality in liver dynamic CT(LDCT) scan, by protocols generally used and the tube voltage set at a low level protocol compared to the radiation dose and image quality. The target is body mass index, 18.5~24 patients out of 40 patients who underwent the ACT(abdominal CT). Group A(tube voltage : 120kVp, SAFIRE strength 1) of 20 people among 40 people, to apply the general abdominal CT scan protocol, group B(tube voltage : 100kVp, apply SAFIRE strength 0~5) was 20 people, set a lower tube voltage. Image quality evaluation was setting a region of interest(ROI) in the liver parenchyma, aorta, superior mesenteric artery (SMA), celiac trunk, visceral fat of arterial phase. In the ROI were compared by measuring the noise, signal to noise ratio(SNR), contrast to noise ratio(CNR), CT number. In addition, qualitative assessments to evaluate two people in the rich professional experience in Radiology by 0-3 points. We compared the total radiation dose, dose length product(DLP) and effective dose, volume computed tomography dose index(CTDIvol). The higher SAFIRE in the tube voltage 100 kVp, noise is reduced, CT number was increased. Thus, SNR and CNR was increased higher the SAFIRE step. Compared with the tube voltage 120kVp, noise, SNR, CNR was most similar in SAFIRE strength 2 and 3. Qualitative assessment SAFIRE strength 2 is the most common SAFIRE strength 2 the most common qualitative assessment, if the tube voltage of 100kVp when the quality of the images better evaluated was SAFIRE strength 1. Dose was reduced from 21.69%, in 100kVp than 120kVp. In the case of a relatively high BMI is not LDCT scan, When it is shipped from the factory tube voltage is set higher, unnecessary radiation exposure when considering the reality that is concerned, when according to the results of this study, set a lower tube voltage and adjust the SAFIRE strength to 1 or 2, the radiation without compromising image quality amount also is thought to be able to be reduced.

• Radiation Oncology Journal
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• v.37 no.4
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• pp.254-258
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• 2019

Purpose: Deep inspiration breath hold (DIBH) is a well-established technique that enables efficient cardiac sparing in patients with left-sided breast cancer. The aim of the current study was to determine if DIBH is effective for reducing radiation exposure of of liver and other organs at risk in right breast radiotherapy (RT). Materials and Methods: Twenty patients with right-sided breast cancer were enrolled in this study. Three-dimensional conformal RT plans were generated for each patient, with two different computed tomography scans of free breathing (FB) and DIBH. Nodes were contoured according to the Radiation Therapy Oncology Group contouring guidelines. Dose-volume histograms for the target volume coverage and organs at risk were evaluated and analyzed. Results: DIBH plans showed significant reduction in mean liver dose (5.59 ± 2.07 Gy vs. 2.54 ± 1.40 Gy; p = 0.0003), V_20Gy (148.38 ± 73.05 vs. 64.19 ± 51.07 mL; p = 0.0003) and V_10Gy (195.34 ± 93.57 vs. 89.81 ± 57.28 mL; p = 0.0003) volumes compared with FB plans. Right lung doses were also significantly reduced in DIBH plans. Heart and left lung doses showed small but statistically significant improvement with application of the DIBH technique. Conclusion: We report that the use of DIBH for right-sided breast cancer significantly reduces the radiation doses to the liver, lungs, and heart.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1177-1182
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• 2005

The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-pro-pyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electro-spray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.47-53
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• 2015

Objectives : This study was performed to investigate the anti-diabetic effect of the fruit extract of Lycium chinense Mill(Lycii Fructus, LF) on multiple low-dose streptozotocin-induced diabetic rats.Methods : Male Sprague-Dawley rats were divided into three groups; normal, STZ-control, Lycii Fructus extractorally administrated 300 ㎎/㎏ group (STZ-LF). Diabetes was induced in rats by consecutive injection of streptozotocin (STZ) at doses of 30 ㎎/㎏ for 5 days. After 4 weeks, all rats were sacrificed, Fasting blood glucose, total cholesterol (CHO), triglyceride (TG) and HDL-Cholesterol were measured in sera of rats. Histopathological changes of pancreas, kidney, liver and lung tissues were observed by microscope after H&E, Periodic acid-Schiff (PAS) and Masson's trichrome staining. The changes of body weight, blood glucose, and food and water intake were also measured.Results : There were no differences in body, food intake and water intake in LF-administrated groups compared with STZ control group. However, LF extract significantly decreased the levels of serum glucose, CHO, TG and HDL-Cholesterol in diabetic rats. In histopathological analysis of kidney, liver and lung, LF-administrated groups showed the inhibition of morphological damage.Conclusions : These results suggest that LF have a biological action on multi low-dose STZ-induced diabetes in rats via decreasing the serum glucose, TG and TG levels and may protect the morphological changes of kidney, liver and lung.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.142-142
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• 1998

This study has been undertaken to examine the effect of biphenyl dimethyl dicarboxylate (DDB) on rat liver drug metabolizing enzyme in order to understand the mechanism of DDB on improving hepatic toxicity in rat liver. After DDB was administered into male rats for different periods of time, mRNA level of CYP1A1 and CYP2B1 was measured by polymerase chain reaction (PCR). DDB treatment resulted in increase in CYP2B1 mRNA level whereas there was no change in CYP1A1 mRNA level. This effect of DDB was time dependent reaching maximal level by 2-day treatment. DDB dose response study showed that 50mg/kg DDB induced CYP2B1 mRNA to maximal level and DDB icreased CYP2B1 gene expression with dose-dependent manner. Based on studies of lipid peroxidation, serum ALT and AST levels and histopathologic examination showed DDB protection on CCl4 induced hepatotoxiccity.

• Toxicological Research
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• v.25 no.2
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• pp.79-84
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• 2009

Cerium oxide nanoparticles (size: 30 nm) were prepared by the supercritical synthesis method, Acute oral toxicity and tissue distribution of the nanoparticles were evaluated by a single administration in rats. Oral administration of the nanoparticles to the rats did not lead to death when the animals were treated by a dose of 5 g/kg (high dose) as well as 100 mg/kg (low dose). Abnormal clinical signs, changes in serum biochemistry and hematology were not observed in high-dose treated group compared to the vehicle control group. Lesions in liver, lung and kidney were not observed in high-dose treated group by histopathological examination. Tissue distribution analysis in liver, kidney, spleen, lung, testis and brain was performed on day 1, day 7 and day 14 after treatment. The average values of the accumulated cerium oxide nanoparticles were elevated in all tissues but statistical significance was only shown in lung. Low levels of tissue distributions after a single oral administration seem to be the low bioavailability of the nanoparticles.

• Korean Journal of Pharmacognosy
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• v.27 no.4
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• pp.397-407
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• 1996

This study was attempted to investigate the effect of Composite Preparation (Sam Whang Sasim-Tang: SWST, Whang Ryun Haedok-Tang: WRHT) on the activities of GOT and GPT, the content of total lipids, triglyceride, total cholesterol. Phospholipid and ${\beta}-lipoprotein$ in the serum, and the change ratio of body and liver weight in the experimentally induced hyperlipemic rats, making use of the extract 150, 200, 300 and 500 mg/kg p.o. Significant test was performed by comparision with the values of corresponding experimentally hyperlipemic rats. The activities of S-GPT was significantly decreased in all dose of SWST and WRHT respectively. The activities of S-GPT was significantly decreased in dose of SWST 500 mg/kg and in all dose of WRHT respectively. The content of total lipids, triglyceride, total cholesterol and phospholipids were significantly decreased in all dose of two the extract. The rate of decrease on total lipids and triglyceride were remarkable in dose of SWST 300, 500 mg/kg and WRHT 200, 500 mg/kg, and then the content of total cholesterol was more remarkable in dose SWST 300, 500 mg/kg, and WRHT 150, 300 mg/kg, and the content of phospholipids was more remarkable in dose of the extract 150, 200 and 300 mg/kg. The content of ${\beta}-lipoprotein$ was significantly decreased in dose of WRHT 150, 200 and in all dose of SWST. Increase ratio of the body and liver weight were significantly decreased in dose of two the extract 300, 500 mg/kg respectively.

• Toxicological Research
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• v.20 no.2
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• pp.143-151
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• 2004

This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SO) rats. In single-dose oral toxicity study, the test article were administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555 resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.

• Journal of Radiation Protection and Research
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• v.34 no.3
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• pp.102-106
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• 2009

We exposed ICR mice to low-dose (0.2 Gy) and low-dose-rate (0.7 mGy/h) $\gamma$-radiation ($^{137}Cs$) in the Low-dose-rate Irradiation Facility at the Radiation Health Research Institute to evaluate systemic effects of low-dose radiation. We compared the body and organ weights, number of blood cells (white and red blood cells and platelets), levels of biochemical markers in serum, and frequency of micronuclei in polychromatic erythrocytes between low-dose irradiated and non-irradiated control mice. The ICR mice irradiated with total doses of 0.2 and 2 Gy showed no changes in body and organ weights, number of blood cells (white and red blood cells), or frequency of micronuclei in the polychromatic erythrocytes of peripheral blood. However, the number of platelets (P = 0.002) and the liver weight (P < 0.01) were significantly increased in mice exposed to 0.2 and 2 Gy, respectively. These results suggest that a low-dose-rate of 0.7 mGy/h does not induce systemic damage. This dose promotes hematopoiesis in the bone marrow microenvironment and the proliferation of liver cells. In the future, the molecular biological effects of lower doses and dose rates need to be evaluated.