• 대한수의학회지
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• 제36권1호
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• pp.221-233
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• 1996

This experiment was carried out to study the toxic effect of solublized methylcellulose (MC). Sprague-Dawley rats were dosed with 1%(w/v) MC in 0.9% saline by gavage at a dose of 10ml/kg b.w/day or by intravenous injection at a dose of 5ml/kg b.w/day for 28 days. Clinical signs were observed once a day. Body weights, water and food consumptions were measured and urinalysis was performed several times during the experiment. Rats were sacrificed on days 3, 7, 15 and 28 for hematology, blood chemistry, organ weights and histopathology. The relative weight of the spleen and foamy cells of the spleen were increased in the gavage group. Body weight gain, food consumptions, the values of RBC, Hb, MCH, Hct, serum proteins, glucose, bilirubin, AST, and ALP were decreased in I.V. treatment group. On the other hand, water consumptions, the values of serum cholesterol, creatinine, and BUN were increased. Microscopic findings were granulomas, distended sinusoids, and hypertrophy of Kupffer cells with vacuoles in the liver. Spleen exhibited granuloma, increased extramedullary hematopoiesis, and congestion. Kidney exhibited foamy cells in the glomeruli, distension of the tubules. The findings appeared more severe when the treatment was extended. In conclusion, MC solution is not a safe vehicle for intravenous administration because of the toxic effects on the liver, kidney and spleen. In addition, a long-term and large dosage of oral administration of MC appears to be unsafe also and needs to be investigated further.

• 환경생물
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• 제27권2호
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• pp.230-236
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• 2009

An extract of Allomyrina dichotoma larva (ADL), one of the insects used most frequently in traditional Chinese medicine for the treatment of liver diseases such as hepatocirrhosis and hepatofibrosis, was assessed for antioxidant bioactivity in this study. In the current work, we have investigated the protective effects of ADL extracts on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in cultured hepa1c1c7 cells and in the mouse liver. The treatment of the hepa1c1c7 cells with ADL extracts induced a significant reduction of t-BHP-induced oxidative injuries, as determined by cell cytotoxicity, lipid peroxidation (LPO) and reactive oxygen species contents, in a dose-dependent manner. Moreover, ADL extracts evidenced a protective effect against t-BHPinduced oxidative DNA damage, as revealed by the results of the Comet assay in hepa1c1c7 cells. ADL extracts also protected against hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and $H_2O_2$. In addition, ADL extracts were shown to be able to quench 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. Our in vivo study revealed that ADL extracts pretreatment applied prior to t-BHP administration significantly prevented an increase in the serum levels of hepatic enzyme markers and reduced LPO in the mouse liver in a dose-dependent manner. Taken together, these results suggest that the protective effects of ADL extracts against t-BHP-induced hepatotoxicity may be attributable, at least in part, to its ability to scavenge free oxygen radicals, and to protect against DNA damage due to oxidative stress.

• 약학회지
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• 제52권5호
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• pp.345-354
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• 2008

This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.

• 약학회지
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• 제43권6호
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• pp.827-833
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• 1999

In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome $P_450$ lAl and 2Bl, and the protective mechanism against $CCl_4-induced$ hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1~7 days) and with different doses (25, 50, 100 and 200 mg/kg), mRNA levels of CYPlAl were measured by polymearse chain reaction (PCR) and assayed the activities of CYPlAl specific ethoxyresorufin-O-dealkylase (EROD) and CYP2Bl specific benzyloxyresorufin-O-dealkylase (BROD). DDB treatment resulted in increase in CYP2Bl mRNA level and BROD activity, whereas there was no change in CYPlAl mRNA level and EROD activity. This effect of DDB was time-and dose-dependent and reached maximal level by 3 day and 200 mg/kg treatment. In addition, rats were pre-treated with DDB at doses of 25, 50 or 100 mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, $CCl_4$ 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on $CCl_4-induced$ hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde(MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50 mg/kg appeared the most protective effect against $CCl_4-induced$ heapatotoxity. These results indicate that DDB stimulates CYP2Bl mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on $CCl_4-induced$ hepatotoxicity may be mediated through free radical scavenging.

• Environmental Analysis Health and Toxicology
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• 제23권4호
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• pp.325-335
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• 2008

The protective effects of the Naringin, on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with Naringin prior to the administration of $CCl_4$ significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with Naringin also significantly prevented the depletion of glutathione (GSH) content in the livers of $CCl_4$-induced mice. However, reduced hepatic glutathione levels was unaffected by treatment with Naringin alone. In addition, Naringin prevented $CCl_4$-induced apoptosis and necrosis, as indicated by a liver DNA laddering. To determine whether caspase-8,-3 pathway involved in $CCl_4$-induced acute liver injury, caspase-8, -3 activities were tested by ELISA. Naringin attenuated $CCl_4$induced caspase-8, -3 activities in mouse livers. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of Naringin on the cytochrome P450 (CYP) 2E1, the major isozyme involved in $CCl_4$ were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CYP2E1-dependent hydroxyl at ion and aniline in a dose-dependent manner. These findings suggest that protective effects of Naringin against the $CCl_4$-induced hepatotoxicity may be due to its ability to block CYP2E1-mediated $CCl_4$ bioactivation and that is also protects against caspase-8, -3 pathway mediated apoptosis.

• 농업과학연구
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• 제51권2호
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• pp.169-178
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• 2024

Cordyceps militaris L. (C. militaris) has been traditionally used as tonic medicine for metabolic syndrome. Cordycepin, has been reported with immunomodulatory, antitumor, and hepatoprotective effect, is the main extract from C. militaris. This study was conducted to evaluate the alcohol degradation and hepatoprotective effect of cordycepin-enriched C. militaris extract (CM) powder in chronic and binge ethanol (ethanol Lieber-DeCarli diet)-fed male C57BL/6 Mice. Cordycepin-enriched C. militaris extract powder was orally administered once daily at dose levels of 0, 125, 250, and 500 mg·kg^-1·day^-1 for 16 days. For evaluating alcohol degradation, ethanol concentration and alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity were measured in serum. Serum ethanol (EtOH) concentration was decreased at CM treated groups, and the activities of ADH and ALDH were increased dose-dependently at CM treated groups compare to EtOH model group. In clinical chemistry, the values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were lower in CM treated groups than those in EtOH model group. Additionally, absolute and relative (to body weight) liver weights were statistically decreased in the CM treated groups compared to the EtOH model group. In conclusion, our study showed that cordycepin-enriched C. militaris extract powder exhibits hepatoprotective effect by upregulating the ADH and ALDH enzyme in an alcoholic liver disease model.

• Radiation Oncology Journal
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• 제19권4호
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• pp.319-326
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• 2001

목적 : 폐, 간 등의 상 복부에 위치한 종양의 방사선 조사 체적은 호흡에 의한 종양의 이동을 포함하는 영역으로 조사 체적이 증가된다. 이로 인하여 방사선 독성 및 정상조직 선량이 증가되며, 호흡으로 인한 환자자세의 변화로 인해 종양의 정확한 위치파악이 어렵게 된다. 본 연구에서는 호흡에 따른 장기 움직임 유형을 분석하여 호흡에 의한 장기의 움직임을 최소화 할 수 있는 호흡운동 감소장치를 고안하고 방사선치료 시 호흡운동 감소장치의 유용성을 평가해 보고자 하였다. 대상 및 방법 : 간암환자 10명을 대상으로 하여 MeV-Green과 벨트, 스티로폼판 등을 사용하여 호흡운동감소장치(respiratory motion reduction device, RRD)를 제작하였다. 내부장기의 이동정도는 모의치료 시에 관찰된 횡경막의 이동 정도로 평가하였으며 앙와위와 복와위 및 RRD의 사용 시 이동정도를 쏠아보았고, 각각의 경우에서 이동정도를 고려하여 방사선치료계획을 수립하였다. 선량체적 히스토그램(dose-volume histogram, DVH)을 통해서 전체 간 용적 중 처방선량의 $50\%$가 조사되는 정상간 용적을 구하였다. 결과 : 호흡에 따른 횡경막의 평균이동거리는 앙와위 자세에서 $16{\pm}1.9\;mm$ 이었고, 복와위 자세에서는 $12{\pm}1.9mm$임을 알 수 있었다. 복와위 자세에서 본원에서 자체 제작한 RRD를 사용한 경우에는 $5{\pm}1.4\;mm$으로 감소되었고, 벨트 고정장치의 추가 사용 시에는 $3{\pm}0.9\;mm$으로 감소하여 총 9 mm 감소함을 알 수 있었다. 방사선치료계획에 따른 DVH에서 처방선량의 $50\%$가 조사되는 정상간의 용적은 호흡운동감소장치를 사용하지 않은 경우에 앙와위 자세에서 $43.7\%$, 복와위 자세에서 $40\%$ 이었고, 호흡운동 감소장치를 사용한 경우에 복와위 자세에서 $30.7\%$, 여기에 벨트 고정장치를 추가 사용하였을 경우에는 $21\%$로서 전체 간 용적 중 방사선에 조사되는 정상 간 용적은 최대 $22.7\%$ 감소됨을 알 수 있었다. 결론 : 호흡에 따른 내부장기의 움직임을 최소화 할 수 있는 RRD를 사용하여 정상조직에 불필요하게 조사되는 방사선을 감소시킬 수 있었다.

• 한국의학물리학회지:의학물리
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• 제24권4호
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• pp.295-302
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• 2013

간암 환자에 대한 세기조절방사선치료(IMRT, intensity modulated radiotherapy) 및 세기조절회전방사선치료(VMAT, volumetric arc therapy)와 나선식토모치료(TOMO, Helical Tomotherapy)에서 2차 암의 원인이 될 수 있는 산란 및 누출선량률을 평가하였다. 5명의 간암 환자에 대해 IMRT와 VMAT, TOMO 치료계획을 실시하여 등중심(iso-center)으로부터 20, 40, 60, 80 cm 위치에서 유리선량계(RPLGD, radiophotoluminescence glass dosimeter)를 이용하여 선량을 측정하였다. 계획표적체적(Planning Target Volume, PTV)에 조사된 단위 선량(Gy)당 측정된 산란 및 누출선량은 IMRT의 경우, 최소 0.01에서 최대 3.13 Gy로 측정 되었고 VMAT에 대해서는 최소 0.03에서 최대 2.35 Gy까지, TOMO에 대해서는 최소 0.04에서 최대 1.30 Gy 까지 측정 되었다. 각 치료법에 대한 평균장기등가선량은 세기조절방사선치료에 대해 세기조절회전방사선 치료와 나선식단층토모치료가 각각 갑상선에서 75%와 51%, 대장에서 75%와 41%, 직장에서 72%와 48%, 전립선에서 76%와 50%로 나왔다. 본 측정을 통하여 산란 및 누출선량은 치료 중심으로부터의 거리에 따라 감소함을 보았으며 TOMO 치료의 경우, 환자치료를 위해 사용하는 모니터단위(MU, monitor unit)가 타 치료법에 비해 상대적으로 큼에도 불구하고 산란 및 누출선량은 크지 않는 것으로 평가되었다.

• 대한수의학회지
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• 제44권4호
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• pp.507-513
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• 2004

Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.

• 대한방사선치료학회지
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• 제27권1호
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• pp.31-43
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• 2015

목 적 : 정위적체부방사선치료(Stereotatic body radiation therapy, SBRT)는 원발성 종양과 전이성 종양의 치료법으로 이용되어진다. SBRT는 높은 선량을 전달하기 때문에 MU(Monitor unit)의 증가로 치료시간이 길어지고 치료계획용적(Planning Target Volume, PTV) 주변의 정상장기를 효과적으로 보호할 수 있는 치료계획이 필요하다. 특히 다중표적의 경우 SBRT를 여러 번에 나누어 치료해야하거나 선량 겹침으로 인한 고 선량 영역(Hot spot)이 생길수도 있다. 본 연구는 다중표적 간암에서 TrueBeam STx(Varian, USA)의 무편평화여과기선질(Flattening filter free, FFF) beam을 이용한 용적변조회전치료(Volumetric modulated arc therapy, VMAT)의 유용성을 평가하고자 한다. 대상 및 방법 : 다중표적 간암의 SBRT를 시행하는 5명의 환자를 대상으로 TrueBeam STx의 10MV FFF beam을 이용한 VMAT과 15MV 편평화여과기선질(Flattening filter, FF) beam을 이용한 입체조형치료(conformal radiotherapy, CRT)계획을 세웠다. 두 치료계획을 비교하기 위하여 선량용적히스토그램(Dose Volume Histogram, DVH)을 이용하여 치료계획용적(Planning Target Volume, PTV), 간, 십이지장, 장, 식도, 척수에 들어가는 선량을 평가하고 전체 MU 값을 비교하였다. 또한 두 치료계획의 치료시간을 비교하기 위하여 Beam on time을 평가하였다. 결 과 : PTV에 대한 처방선량지수(Conformity Index, CI), 선량균질지수(Homogeneity index, HI), 처방선량포함지수(Paddick's Conformity Index, PCI)의 평균값은 VMAT에서 각각 $1.006{\pm}0.028$, $1.098{\pm}0.016$, $1.132{\pm}0.084$, CRT에서 $1.381{\pm}0.419$ $1.136{\pm}0.042$, $1.534{\pm}0.465$로 평가되었다. 정상장기에 대한 선량은 CRT에서 VMAT 보다 약 1.8배 높은 선량으로 평가되었다. 전체 MU값은 VMAT에서 약 1.3배 높게 평가되었고 VMAT과 CRT 두 치료계획의 평균 Beam on time은 각각 6.8분, 21.3분으로 평가되었다. 결 론 : 다중표적 간암의 정위적체부방사선치료에서 FFF Beam을 이용한 VMAT을 적용하면 선량 겹침 없이 다중표적을 한 번에 치료할 수 있으며 PTV의 선량포함을 만족하면서 주위의 정상장기를 더 효과적으로 보호할 수 있는 치료계획이 가능하다. 또한 FFF Beam의 높은 선량률(Dose rate)을 이용하여 치료시간을 단축시켜 치료 중 발생할 수 있는 오차를 감소시킬 수 있다.