• Journal of Ginseng Research
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• v.41 no.2
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• pp.159-168
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• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.37-46
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• 1998

It has been known that $\gamma$-irradiation usually induces cell death in regenerating stem cell in normal tissues like skin, intestine and hematopoietic organ. The experiment were carried out to evaluate the early response of radiation injury in radiosensitive and intermediate radiosensitive tissues in feeding and starving rats with the doses of 3.5 and 7.0 Gy. The results of the study showed that the histological phenomenon was apoptosis in the doses of the radiation as the early response of tissue injury. Apoptosis were showed organ-specific and cellular specific responses suggesting that the selection of apoptosis be exactly focused on highly renewal organs and cells. It was interesting that the rats starved for 72 hours prior to irradiation induced less apoptosis in liver than fed rats. As for cellular responses it appeared that apoptotic cells were mostly distributed in ductal or periportal cells in liver of feeding rats unlikely in liver of Starving rots which showed no difference in zonal distribution. In salivary gland apoptotic cells in fed rats were highly induced in intercalating and ductal cell population than in acinar cell population although unlikely in starved rats. This study showed the value of apoptosis using the detection system of TUNEL for evaluating cellular damage after radiation injury and the diminished effect of starvation on cell damage after ionizing irradiation.

• Journal of Radiation Industry
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• v.7 no.1
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• pp.81-85
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• 2013

This study was conducted to investigate the effect of fermented blackberry drinks (BD) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into four groups with 6 rats per group: control, $CCl_4$, $CCl_4$ plus BD $3ml\;kg^{-1}$, and $CCl_4$ plus BD $6ml\;kg^{-1}$. We found that the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased and the activity of antioxidant enzyme glutathione peroxidase (GPx) in the liver was decreased in rats treated with $CCl_4$ alone when compared with the control group. However, the administration of BD attenuated the levels of serum AST and ALT in $CCl_4$-treated rats. Moreover, the administration of BD significantly increased the activity of GPx in $CCl_4$-treated rat livers. Taken together, these results suggest that BD could protect the liver from $CCl_4$-induced hepatic damage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.6
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• pp.807-813
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• 2014

The objective of the present study was to investigate the protective effects of anthocyanin-enriched extract from radiation-induced blackberry (Rubus fruticosus L.) mutant (${\gamma}$-B201) against carbon tetrachloride ($CCl_4$)-induced liver injury in Spargue-Dawley (SD) rats. The in vivo results show that ${\gamma}$-B201 attenuated the levels of serum aspartate aminotransferase, alanine aminotransferase, and liver lipid peroxidation in $CCl_4$-treated SD rats. Histopathological examination of rat livers showed that ${\gamma}$-B201 reduced the incidence of liver lesions induced by $CCl_4$. Moreover, ${\gamma}$-B201 prevented DNA damage in $CCl_4$-treated SD rats. Furthermore, administration of ${\gamma}$-B201 significantly increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), in $CCl_4$-treated rat livers. In conclusion, the present study suggests that ${\gamma}$-B201 blackberry extract protects the liver from $CCl_4$-induced hepatic damage through an antioxidant mechanism. Therefore, ${\gamma}$-B201 blackberry may be functional food material for human health.

• Journal of radiological science and technology
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• v.12 no.1
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• pp.3-16
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• 1989

In order to investigate the in vivo effect of $^{60}Co$ radiation on rabbit liver, the uptake ratio and regional excretory value in hepatocytes and Kupffer cells were estimated during acute and chronic hepatic injuries. The left lobe of liver was irradiated at 15 Gy or 30 Gy with a single dose and subsequent changes were analysed with a seial nuclear medicine imaging by using $^{99m}Tc-phytate,\;^{99m}Tc-DISIDA\;and\;^{99m}Tc-HSA$ and resulting data were computerized. The degree of hepatic damage, duration of the injury, and recovery pattern after the irradation were in agreement with the findings of other investigations. However, out values were more quantitative evacuation than those of other publications. Recovery of decreased uptake of $^{99m}Tc-phytate$ was delayed approximately $2{\sim}3$ days later than that of $^{99m}Tc-DISIDA$. In acute radiation induced injury, the results demonstrated that the recovery of Kupffer cells was delayed more than that of hepatocytes. This discrepancy was considered due to the differences in repair activities between these cell types. The decreased of regional excretory value in irradiated area was found to be dose-dependent but had no corelation with regional uptakes of DISIDA and phytate. The decreased of regional excretory value observed in non-irradiated region suggested that irradiated liver might induce an indirect effect.

• Progress in Medical Physics
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• v.4 no.2
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• pp.69-76
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• 1993

In order to investigate radiation effects on the liver, functional changes of liver were analyzed after irradiation. Doses of 10 Gy, 15 Gy and 20 Gy were exposed partially to the liver of male rats(Sprague-Dawley) with X-ray(4MV linear accelerator) at room temperature. On 1, 2, 4 and 8 weeks after irradiation, sera of the animals were compared with those of unirradiated animal by liver function tests. Enzyme activities in sera such as alkaline phosphatase and concentrations of bilirubin in liver function tests. The content of the activities of many enzymes including alkaline phosphatase in sera were increased slightly with increasing exposure dose in all experiments and the activities of these enzymes increased markedly in 20 Gy irradiated groups. The contents of serum bilirubins including direct and indirect bilirubins increased continuously along with the time lapse after irradiation. However, in 20 Gy irradiated group, the content of serum bilirubin decreased slightly during 2 or 4 weeks after irradiation and increased markedly there after. From these above results, functional changes of the liver were induced in all irradiated groups. Damaged liver was recovered along with time collapsed after irradiation to the doses of 10 Gy and 15 Gy while no recovery was deteced within 8 weeks after irradiation to 20 Gy. These results suggest that careful attontion must be paid to liver not to be included in exposure field in radiation therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4711-4715
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• 2013

Aim: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensitymodulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. Methods: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. Results: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ${\geq}$ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival ($X^2$ = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). Conclusions: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.177-183
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• 2011

The radioprotective efficacy of a methanol extract of the red algae Polyopes lancifolia (Harvey) kawaguchi et wang (mPL) was evaluated in mice subjected to total-body gamma irradiation. mPL protection against radiation-induced oxidative stress was examined by histological evaluation of intestinal crypt-cell survival and liver activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). mPL (100 mg/kg body weight) administered intraperitoneally at 24 h and 1 h prior to irradiation protected jejunal crypt cells from radiation-induced apoptosis (p < 0.01). The pretreatment of mPL attenuated a radiation-induced decrease in villous height (p < 0.05), and improved jejunal crypt survival (p < 0.05). The dose reduction factor was 1.14 at 3.5 days after irradiation. Treatment with mPL prior to irradiation resulted in significantly higher (p < 0.01) levels of SOD and CAT activities, compared to those levels of irradiated control mice with vehicle treatment. These results suggest that mPL is a useful radioprotective agent capable of defending intestinal progenitor cells against total-body irradiation, at least in part through mPL antioxidative activity.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.791-798
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• 2005

The hepatoprotective activity of flavonol glycosides rich fraction (F-2), prepared from 70% alcohol extract of the aerial parts of V calcarata Desf., was evaluated in a rat model with a liver injury induced by daily oral administration of $CCl_4$ (100 mg/kg, b.w) for four weeks. Treatment of the animals with F-2 using a dose of (25 mg/kg, b.w) during the induction of hepatic damage by $CCl_4$ significantly reduced the indices of liver injuries. The hepatoprotective effects of F-2 significantly reduced the elevated levels of the following serum enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant activity of F-2 markedly ameliorated the antioxidant parameters including glutathione (GSH) content, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), plasma catalase (CAT) and packed erythrocytes glucose-6-phosphate dehydrogenase (G6PDH) to be comparable with normal control levels. In addition, it normalized liver malondialdehyde (MDA) levels and creatinine concentration. Chromatographic purification of F-2 resulted in the isolation of two flavonol glycosides that rarely occur in the plant kingdom, identified as quercetin-3,5-di-O-$\beta$-D-diglucoside (5) and kaempferol-3,5-di-O-$\beta$-D-diglucoside (4) in addition to the three known compounds identified as quercetin-3-O-$\alpha$-L-rhamnosyl- (${\rightarrow}6$)-$\beta$-D-glucoside [rutin, 3], quercetin-3-O-$\beta$-D-glucoside [isoquercitrin, 2] and kaempferol-3-O-$\beta$-D-glucoside [astragalin, 1]. These compounds were identified based on interpretation of their physical, chemical, and spectral data. Moreover, the spectrophotometric estimation of the flavonoids content revealed that the aerial parts of the plant contain an appreciable amount of flavonoids (0.89%) calculated as rutin. The data obtained from this study revealed that the flavonol glycosides of F-2 protect the rat liver from hepatic damage induced by $CCl_4$ through inhibition of lipid peroxidation caused by $CCl_4$ reactive free radicals.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.531-538
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• 2004

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-a, IL-1$\beta$, IL-2, IL-6, IL-12, IFN-${\gamma}$ and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1$^{st}$-5$^{th}$ days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7-2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.d.