• Herbal Formula Science
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• v.26 no.3
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• pp.207-221
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• 2018

Objectives : Present study investigated hepatoprotective effect of Haegan-jeon extract (HE) and tried to elucidate molecular mechanism involved. According to molecular mechanism, present study optimized herbal composition of HE (op-HE) and compared in vitro and in vivo hepatoprotective effects of op-HE to HE. Methods : For in vitro experiments, HepG2 cells were exposed to arachidonic acid (AA, $10{\mu}M$) and iron ($5{\mu}M$) for inducing oxidative stress. Cell viability, GSH contents, $H_2O_2$ production, mitochondrial membrane potential, immunoblot and reporter gene assay were performed to investigate cytoprotective effects and responsible molecular mechanisms. For in vivo experiments, hepatoprotective effect of HE and op-HE were assessed on $CCl_4-induced$ liver injury mice model. Results : HE pretreatment prevented AA+iron-mediated hepatocytes apoptosis. In addition, AA+iron-induced mitochondrial dysfunction, $H_2O_2$ production, glutathione depletion were reduced by HE pretreatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation, antioxidant response element (ARE)-driven reporter gene activity, and antioxidant genes expression were increased by HE. Based on reporter gene and MTT assays, we found that op-HE consisting three medicinal herbs also significantly increased transactivation of Nrf2 and reduced the AA+iron-mediated cytotoxicity. Moreover, in $CCl_4-induced$ liver injury mice model, HE-op had an ability to ameliorate $CCl_4-mediated$ increases in serum alanine transferase and aspartate aminotransferase activity, hepatic degeneration, inflammatory cell infiltration, and collagen deposition. Hepatoprotective effects of op-HE were comparable to those of HE. Conclusions : Present study suggests that op-HE as well as HE exhibit hepatoprotective effect against oxidative stress-mediated liver injury via Nrf2 activation.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.103-110
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• 1999

A thromboembolic event in patients later given a diagnosis of cancer is the result rather than the cause of the cancer. The risk of hidden cancer is significantly higher for patients with recurrent idiopathic thromboembolism compared to those with secondary deep vein thrombosis. Microemboli from hepatic or adrenal metastases and large-sized emboli from the great veins invaded by the tumor are the sources of tumor embolization The intraarterial tumor emboli less likely invade the arterial wall. Thrombus formation and organization may be capable of destroying tumor cells within pulmorlary blood vessels. Therefore, all tumor emboli are not true metastases. The treatment of deep vein thrombosis and pulmonary embolism in patients with cancer consists of anticoagulation with heparin and warfarin, venacaval filters, appropriate anti-neoplastic agents, and surgical methods(embolectomy, thromboendarterectomy). However, considerable literatures suggest that oral anticoagulant such as warfarin is ineffective in the treatment of those. We report a case of primary unknown squamous cell carcinoma incidentally found in the thrombus after pulmonary embolectomy.

• Journal of Pharmacopuncture
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• v.12 no.4
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• pp.63-76
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• 2009

This study was performed to observe the effect of Keughachukeo-tang(KH) extract on the hepatocellular carcinogenesis and acute liver damage induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into four; normal group(Nor), acute liver damage and hepatocellular cancer inducing control group(Con), KH extract 350㎎/㎏/day(KHA), and 700㎎/㎏/day(KHB) administered groups to Con. The results obtained are as follows: The body weight increased in KHA and KHB than Con from 7th week to the 8th week. The activities of Alanine aminotransferase(ALT) were the most increased in the Con among experimental group. The activities of aspartate aminotransferase(AST), alkaline phosphatase(ALP), and lactacte dehydrogenase(LDH) were significantly decreased(p$<$0.05) in the KHA and KHB compared with Con. Alpha fetoprotein(AFP) were the most increased in the Con among experimental groups. The activities of superoxide dismutase(SOD) were the most increased in the Con among experimental groups. The activities of catalase were significantly increased(p$<$0.05) in the KHA and KHB compared with Con. The results of light microscopical observation, a number of hepatocytes were damaged in the Con compared with Nor and KH extract administerd groups. The number of hepatic p53 positive cells was reduced in the KH extract administered groups compared with Con. These results suggest that administration of KH extract suppress or retard on the Hepatocellular Carcinogenesis and acute liver damage induced by DENA and $CCl_4$ in Rats.

• Journal of Embryo Transfer
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• v.28 no.2
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• pp.157-162
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• 2013

Methoxychlor (MXC) was developed to be a replacement for the banned pesticide DDT. HPTE [2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane], which is an in vivo metabolite of MXC, has strong oestrogenic and anti-androgenic effects. MXC and HPTE are thought to produce potentially adverse effects by acting through oestrogen and androgen receptors. Of the two, HPTE binds to sex-steroid receptors with greater affinity, and it inhibits testosterone biosynthesis in Leydig cells by inhibiting cholesterol side-chain cleavage enzyme activity and cholesterol utilisation. In a previous study, MXC was shown to induce Leydig cell apoptosis by decreasing testosterone concentrations. I focused on the effects of MXC on male mice that resulted from interactions with sex-steroid hormone receptors. Sex-steroid hormones affect other organs including the kidney and liver. Accordingly, I hypothesised that MXC can act through sex-steroid receptors to produce adverse effects on the testis, kidney and liver, and I designed our experiments to confirm the different effects of MXC exposure on the male reproductive system, kidney and liver. In these experiments, I used pre-pubescent ICR mice; the puberty period in ICR mice is from postnatal day (PND) 45 to PND60. I treated the experimental group with 0, 100, 200, 400 mg MXC/kg b.w. delivered by an intra-peritoneal injection with sesame oil used as vehicle for 4 weeks. At the end of the experiment, the mice were sacrificed under anaesthesia. The testes and accessory reproductive organs were collected, weighed and prepared for histological investigation. I performed a chemiluminescence immune assay to observe the serum levels of testosterone, LH and FSH. Blood biochemical determination was also performed to check for other effects. There were no significant differences in our histological observations or relative organ weights. Serum testosterone levels were decreased in a dose-dependent manner; a greater dose resulted in the production of less testosterone. Compared to the control group, testosterone concentrations differed in the 200 and 400 mg/kg dosage groups. In conclusion, I observed markedly negative effects of MXC exposure on testosterone concentrations in pre-pubescent male mice. From our biochemical determinations, I observed some changes that indicate renal and hepatic failure. Together, these data suggest that MXC produces adverse effects on the reproductive system, kidney and liver.

• Journal of Acupuncture Research
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• v.28 no.5
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• pp.39-55
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• 2011

Objectives : Inchinohryungsan has been used for treatment of hepatobiliary diseases. This study was designed to investigate the effect of Inchinohryungsan pharmacopuncture on hepatocellular carcinoma in rats. Sprague Dawley(SD) rats of the control and experimental groups received intraperitoneal injection of 50 mg/kg DEN, weekly for 12 weeks. Methods : Rats were divided into 5 groups. Normal group was not induced hepatocellular carcinoma and not treated. Control group was induced hepatocellular carcinoma and injected with Inchinohryungsan pharmacopuncture into the root of tail. Experimental groups were induced hepatocellular carcinoma. BL group was injected with Inchinohryungsan pharmacopuncture into the $BL_{18}$ and $LR_{14}$, BG group was injected into the $BL_{19}$ and $GB_{24}$ and CSC group was injected into the $CV_{12}$, $ST_{25}$ and $CV_4$. Thereafter, the changes of the body weight, the liver weight and the weight of liver/100g body weight, WBC, neutrophil, lymphocyte and the activities of AST, ALT, ALP, LDH, AFP and SOD were measured. And gross anatomy, light and electron microscopy were performed. Results : The significant results were as follows, 1. The activities of LDH were significantly decreased in CSC group compared with control group. 2. The activities of AFP were significantly decreased in the BL, BG, CSC groups compared with control group. 3. The activities of SOD were increased in the BL, BG, CSC groups compared with control group and CSC group was significantly increased than normal group. 4. According to the gross anatomical observation, the control and BL, BG, CSC groups showed multi-nodular hepatocellular carcinoma. But the size and numbers of the hepatocellular carcinoma in experimental groups were smaller than control group. 5. The numbers of hepatic p53 positive cells were decreased in the BL, BG groups compared with control group. 6. According to the light and electron microscopical observation, the BL, BG and CSC groups were mildly improved than control group in morphological and histopathological changes. Conclusions : These results suggested that Inchinohryungsan pharmacopuncture may have some effects on hepatocellular carcinoma induced by DEN in rats.

• Toxicological Research
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• v.21 no.4
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• pp.339-345
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• 2005

Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin $B_1\;(AFB_1)$ is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types $(AFB_2,\;AFG_1\;and\;AFG_2)$ of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1,\;AFB_2,\;AFG_1\;and\;AFG_2$ at the dose of 250, 1250, and $2500\;{\mu}g/kg$ body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of $AFB_1\;and\;AFG_1$ was significantly low. The treatment of $AFB_1$ at the high dose of $2500\;{\mu}g/kg$ showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by $AFB_2\;AFG_1,\;and\;AFG_2$ were not clearly found. 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 the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by $AFB_1$ at the dose of $1250\;{\mu}g/kg$ was increased twice compared to the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ at all doses decreased the expression of ras in the liver. 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 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to $AFB_1$ in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.

• Journal of Preventive Medicine and Public Health
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• v.24 no.3 s.35
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• pp.287-304
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• 1991

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), $CdCl_2$ (0.5 mg/kg, B), and $ZnCl_2$ (13.0 mg/kg, C) during time periods of $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

• Korean Journal of Food Science and Technology
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• v.52 no.1
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• pp.89-93
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• 2020

Vibrio vulnificus, an opportunistic pathogen, causes septicaemia when raw shellfish and fish are eaten by patients with hepatic diseases or reduced immunity. In this study, we evaluated inhibitory effects of some natural products on V. vulnificus growth using 96-well microplate assay. We found that Phyllanthus emblica L., Rosa chinensis Jacq., Rosa rugose Thub., and Chukrasia tabularis A. Juss. significantly inhibited V. vulnificus growth in Luria-Bertani (LB) broth. Among these four extracts, the inhibition diameter of Chukrasia tabularis was 16.00 ± 0.58 mm in disc diffusion assay on V. vulnificus growth. In addition, these four natural products protected HeLa cells from V. vulnificus-induced cytotoxicity. A cocktail containing these four products showed an inhibitory effect on V. vulnificus growth in seawater and shellfish by reducing its growth by 75.7% and 97%, respectively. These results suggest that these four natural products are safe and effective natural antimicrobial candidates to prevent V. vulnificus infection.

• Journal of Food Hygiene and Safety
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• v.17 no.1
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• pp.8-14
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• 2002

Cotinine, one of nicotine metabolites, has been blown to reduce 4-(methylnitro samino)-1-(3-pyridyl)-1-butanone(NNK)- induced $O^{6}$MeG DNA adducts significantly in A/J mice when administered together with NNK. In order to examine the effects of phyto-extract mixture on the conversion of cotinine from nicotine, cellular and clinical experiments were carried out. When the phyto-extract mixture was added to culture media, human liver cells (FLCFR5) produced cotinine from nicotine 2~3 times compared to the control. The phyto-extract mixture which was microinjected into Xenopus oocyte along with nicotine showed the almost similar production of cotinine compared with the results of hepatic cell culture. In clinical test employing 17 to 20 healthy men, concentrations of urinary cotinine derived from smoking after taking photo-extract mixture increased up to 2 times compared to the control group. These results indicatethat the phyto-extract mixture can increase the metabolic efficiency of nicotine to cotinine, leading to the reduced formation of $O^{6}$MeG DNA adducts.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.30 no.5
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• pp.823-833
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• 1997

To clarify the annual reproductive cycle of the banded catfish, Pseudobagrus fulvidraco (Richardson), the seasonal changes in histological aspect of gonad and liver were examined. The adult fish was raptured from the upper stream of Young-San river, Chunnam in each month from May 1992 to June 1993. Based on the annual changes in GSI (gonadosomatic index), HSI (hepatosomatic index), CF (condition factor) and histological aspects of the gonads, the annual reproductive cycle were classified into 5 periods as follows: 1) Growing phase (from April to early May): The value of GSI increased and the size of oocytes in perinucleolus stage in oocytes increased gradually. Spermatogonia were developed actively from the epithelial tissues of seminiferous tubules. 2) Maturing phase (from Hay to early June): GSI levels increased rapidly in both sex. Oocytes at various developmental stages were observed. Appearance of active spermatogenesis were observed. 3) Mature and spawning phase (from June to August): High values of GSI remained static and oocytes accumulated significant quantitis of yolk globules. 4) Degenerating phase (from September to November): GSI levels decreased and ovaries were filled mostly with oocytes at the perinucleolus stage. Hepatic cells accumulated significant amounts of lipid droplets. 5) Resting period (from December to March) : Low values of GSI were kept and the size of oocytes at the perinucleolus stage did not increase. Spermatogenesis was not observed.