• Molecular & Cellular Toxicology
• /
• 제1권4호
• /
• pp.268-274
• /
• 2005

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.

• Molecular & Cellular Toxicology
• /
• 제1권4호
• /
• pp.275-280
• /
• 2005

Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

• Applied Microscopy
• /
• 제36권4호
• /
• pp.235-250
• /
• 2006

본 연구는 급성 납 독성에 대한 활성탄의 방어효과를 알아보기 위하여 시도되었다. 30g내외의 생쥐를 대상으로 대조군, 납(60mg/kg) 투여군, 납 투여 후 활성탄(40mg/kg) 투여군으로 구분하여 구강투여 한 후 간장, 신장손상 억제 효과를 알아보기 위하여 생화학적 및 조직학적 실험을 실시하였다. 혈액중 aspartate amiotransferase(AST). alanine amino-transferase(ALT)그리고 glucose(Glu)의 수치는 활성탄 투여군이 납 투여군보다 감소되었다. 전자현미경적 관찰 결과, 간장에서 납 투여군은 간세포의 핵이 함입되어 불규칙했으며 미토콘드리아와 조면소포체의 수조가 팽대되고, 리보솜의 탈락이 관찰되었다. 활성탄 투여군은 핵이 대조군과 같은 형태가 관찰되었고, 전자밀도가 높은 미토콘드리아가 분포되어 있었으며, 리보솜이 부착된 상태로 층판구조를 형성하는 조면소포체가 관찰되었다. 이상과 같은 결과, 활성탄이 납 중독된 생쥐에서 납을 흡착시킴으로서 손상된 간장에 보호 효과가 있는 것으로 사료된다.

• 대한본초학회지
• /
• 제26권3호
• /
• pp.47-56
• /
• 2011

Objectives : This study investigated whether the water extract of Spatholobi Caulis (SCE) has the ability to protect hepatocyte against oxidative stress induced by tert-butylhydroperoxide (tBHP) in vitro and $CCl_4$ in vivo. Methods : In vitro, HepG2 cells pre-treated with Spatholobi Caulis water extract (1, 3, 10, $30{\mu}g$/ml) for 12h and further incubated with tBHP ($100{\mu}M$) for the next 12h. Cell viability was assessed by MTT assay. In vivo, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, injected with $CCl_4$ 1 mg/kg body weight to induce acute liver damage. Results : Treatment with SCE inhibited cell death induced by tBHP, as evidenced by alterations in the levels of the proteins associated with apoptosis:SCE prevented a decrease in $Bcl_2$, and cleavage of poly(ADP-ribose)polymerase and pro-caspase-3. Moreover, SCE inhibited the ability of tBHP to generate $H_2O_2$ production, thereby restoring GSH content. Moreover, SCE treatments in rats effectively decreased liver injuries induced by a single dose of $CCl_4$, as evidenced by decreases in hepatic degeneration and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. Consistently, treatments of SCE also protected liver in rats stimulated by $CCl_4$, as indicated by restoration GSH and prevention of MDA in the liver. Conclusions : SCE has the ability 1) to protect hepatocyte against oxidative stress induced by tBHP and 2) to prevent $CCl_4$-inducible acute liver toxicity. Present findings may be informative not only in elucidating the pharmacological mechanism of Spatholobi Caulis, but in determining its potential application for oxidative cellular damage in the liver.

• Fisheries and Aquatic Sciences
• /
• 제9권1호
• /
• pp.14-21
• /
• 2006

The aim of this study was to investigate in vivo toxicity and effects of two phthalate esters (PEs), di-n-butylphthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), on the immune system of the bagrid catfish, Pseudobagrus fulvidraco. Groups of experimental fish were subjected to daily intraperitoneal injections of 300 or 1000 mg $kg^{-1}$ of DBP or DEHP for 3 days, and the cellularity and functional activity of phagocytes were measured in the spleen and pronephros (head kidney). The number of spleen leukocyte cells increased significantly (p<0.05) in response to low and high doses of DEHP and DBP, respectively; however, the cellularity of the pronephros was more susceptible to higher dose of DEHP than DBP. Nonspecific immunity, as determined by the phagocytic index (PI) and phagocytic capacity (PC), was significantly depressed by DEHP at 1000 $1000mg\;kg^{-1}\;day^{-1}$ in the pronephros at 3 days after injection. Furthermore, significantly (p<0.05) increased levels of serum glutamic oxaloacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT) indicated marked hepatic dysfunction in immunosuppressed fish. Treated fish showed a significant reduction in total serum protein but no significant alteration in lysozyme activity. These results demonstrate the sensitivity of the fish immune response for predicting PE-induced immunotoxicity.

• 한국식품영양과학회지
• /
• 제18권3호
• /
• pp.273-278
• /
• 1989

해동피 methanol 추출물을 시료로 mouse의 급성독성실험, 실험적으로 유발시킨 가토의 간장기능 장애에 미치는 영향을 실험하여 다음과 같은 결과를 얻었다. 실험결과 해동피 methanol 추출물의 급성독성 $(LD_{50})=7.3g/kg$으로 무독하였고 $CCI_4$로 손상시킨 가토의 간장기능회복에 있어서는 실험동물체중 kg당 시료 800mg투여군에서 14일째 대조군에 비해 SGPT가 $87.28{\pm}23.03$ unit로 서서히 유의성있게 회복되었다. 시료 800mg/kg투여군에서 alkaline phosphatase 활성도는 2일째부터, 그리고 total bilirubin 측정치는 6일째부터 현저히 회복되는 경향을 보였다. 특히 total cholesterol 측정치는 200mg/kg투여군에서 14일째 $99.36{\pm}12.42mg/d{\ell}$과 800mg/kg투여군에서 10일째 $96.69{\pm}18.40mg/d{\ell}$, 14일째 $80.68{\pm}8.77mg/d{\ell}$로 대조군에 비해 현저한 감소를 보였다.

• 수산해양교육연구
• /
• 제28권6호
• /
• pp.1573-1580
• /
• 2016

The disease occurred in cultured eel (Anguilla japonica) in a recirculatory culture system without any separated filtration apparatus. As the pond had a high level of nitrite with $60mg/{\ell}$, 1% NaCl was added to reduce nitrite toxicity to eel. The first outbreak was observed a week after the NaCl treatment and continued for 10 days. Accumulated mortality was about 0.2-0.5%. Affected fish ranged from 150-350 g were usually anorexic and exhibited yellow colour in the skin of the abdominal region and at the base of pectoral fins, as well as in the eyes. In a few individuals with severe symptoms, the lateral skin was also yellowish. The spleen, kidney, muscle and gall bladder were yellowish and the liver was pale-yellow colour but green on the posterior part. The gall bladder was shrunken without bile. Some abnormal erythrocytes such as "tear drop" cells (dacrocyte) were observed in peripheral blood smears stained with May-Grunwald Giemsa. Hematocrit values and hemoglobin contents in the jaundiced eel were significantly lower compared with apparently heathy eel. Severe haemosiderosis accompanied by erythrophagocytosis was found in the kidney and spleen. Haemosiderin deposits were observed in macrophages of the haematopoietic tissue of the kidney and in the splenocytes. But no significant alterations were found in the hepatic cells. In this study we report the first outbreak of jaundice in cultured eel in Korea. Pathological and hematological investigations suggested that severe hemolysis may resulted in jaundice in eel although the cause of hemolytic jaundice was not identified in this study.

• 혜화의학회지
• /
• 제18권1호
• /
• pp.83-88
• /
• 2009

Recently, herbal drugs haver been used world wide. and generally regarded as safe with no serious adverse reaction. Drug-induced liver injury (DILI) is one of frequent cause of liver diseases. If DILI is not treated, it can be developed into liver cirrhosis, hepatoma, etc. Currently, DILI has been reported to be common cause of acute hepatitis, and oriental medicine and folk remedy are not exception. We encountered one case of DILI, cause by folk remedy. Patients complained chest discomfort, yellow skin and urine, nausea, vomiting. Lab test showed elevated level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (r-GTP), total bilirubin (TB). We estimated acute DILI and stopped taking folk medication made by himself. After 1 week of treatment, the clinical symptoms and liver function improved. Genetic and environmental factors as well as drug itself decide the hepatic toxicity, and the major DILI are belonged in acute type. So we need to get more attention to folk medication to help preventing the DILI cause by folk remedy.

• Journal of Ginseng Research
• /
• 제35권2호
• /
• pp.162-169
• /
• 2011

The mixture of Ginseng Radix and Crataegi Fructus (Gen-CF) was developed to increase the pharmacological effect of ginseng in the treatment of hypercholesterolemia and prevention of cardiovascular disease. This study evaluated the effects of Gen-CF on serum lipids of hypercholesterolemic rats in vivo, as well as its antioxidant activities in vitro, and explored its clinical effects on patients with hypercholesterolemia. In vitro, Gen-CF displayed 1,1-diphenyl-2-picrylhydrasyl and superoxide radical scavenging activities, and inhibited hemolysis induced by 2,2'-azobis-2-amidinopropane dihydrochloride in a dose-dependent manner. In vivo, Gen-CF significantly inhibited the increases of total cholesterol, low-density lipoprotein cholesterol and triglyceride in high cholesterol-diet and Triton WR-1339 models. It also significantly inhibited the decrease of high-density lipoprotein cholesterol in these models. In the clinical trial, Gen-CF significantly lowered total cholesterol, low-density lipoprotein cholesterol, triglyceride, total lipid and phospholipid, with no adverse events, including hepatic or renal toxicity. The data suggest that Gen-CF has the potential to treat hypercholesterolemia and prevent cardiovascular disease.

• 대한한방내과학회지
• /
• 제22권2호
• /
• pp.251-256
• /
• 2001

In western medicine, there are some reports about herbal medicine induced hepatitis, but in oriental medicine, there are few reports about that. We experienced one case of drug acute cholestatic-hepatitis in the treatment of oriental medicine for HNP. We treated the patient with acupuncture, physical therapy and herb medicine. The patient's symptoms improved after two weeks of treatment. In the course of treatment, the patient intermittently complained of general weakness, nausea, yellowish urin, dyspepsia, and abdominal discomfort. We recognized that total bilirubin(7.2mg/dl), direct bilirubin(5.5mg/dl), serum transaminase(AST 360U/L, ALT 354U/L), alkaline phosphatase(16.6 K/A), urobilinogen(++) and bilirubin(++) were elevated. We diagnosed drug induced hepatitis. We stopped giving herb medicine and began giving Saeng gan gunbi-tang and Injin-oryung-san. Saeng gan gunbi-tang and Injin-oryung-san have been used to treat hepatic disease and have been known to have beneficial effects. After 3weeks on medication, the clinical symptoms and liver function improved. So, we report this case to bring more attention to the safety and toxicity of herbal medicine.