• Environmental Analysis Health and Toxicology
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• v.19 no.4
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• pp.359-366
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• 2004

Iron (Fe) is an essential metal in biological processes, which maintains a homeostasis in the human body. Divalent metal transporter 1 (DMT1) has been known as an iron transporting membrane protein, which is involved in the uptake Fe at the apical portion of intestinal epithelium, and may transport Fe across the membrane of acidified endosome in peripheral tissues. In this study, we studied the tissue distribution of DMT1 in the Fe supplemented (FeS) diet fed rats, and the regulation of DMT1 expression by depleting body Fe. Sprague-Dawley rats were divided into two groups, and fed FeS (120 mg Fe/kg) diet or Fe deficient (FeD, 2∼6 mg Fe/kg) diet for 4 weeks. The evaluation of body Fe status was monitored by measuring sFe, UIBC and tissue Fe concentration. Additionally, DMT1 mRNA levels were analyzed in the peripheral tissues by using the quantitative real time RT-PCR method. In the FeS diet fed rats, the tissue Fe was maintained at a relatively high level, and DMT1 was eventually expressed in all tissues studied. DMT1 was highly expressed in the testis, kidney and spleen, while a moderate levels of DMT1 expression was detected in the brain, liver and heart. In the digestive system, the highest level of DMT1 was found in the duodenum. Feeding the FeD diet caused a reduced body weight gain and depletion of body Fe with finding of decreased sFe, increased UIBC and decreased tissue Fe concentration. The depletion of body Fe upregulated DMT1 expression in the peripheral tissue. The expression of DMT1 was very sensitive to the body Fe depletion in the small intestine, especially in the duodenum, showing dramatically higher levels in the FeD rats than those of the FeS group. In the FeD diet fed animals, the expression of DMT1 was low significantly in other tissues compared with the duodenum. The expression of DMT1, however, was 60∼120% higher in the testis, kidney and spleen, and 30∼50% higher in the lung, liver and heart, compared to the FeS diet fed rats. In summary, DMT1 expression was ubiquitous in mammalian tissue, and the level of expression was the organ-dependent. The expression of DMT1 in peripheral tissues was upregulated by depletion of body Fe. Duodenum was the most sensitive tissue among organs studied during Fe depletion, and expressed the greatest level of DMT1, while other tissues were less higher than in duodenum. This study supports that DMT1 plays a role in maintaining the body Fe level through intestinal uptake as well as homeostasis of Fe in the peripheral tissue.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.863-870
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• 2008

The aim of this study was to investigate that Injinoryung-san-Ga-Samchilgun(IJORS) has an inhibitory effect on the development of liver fibrosis in rats. The influence of IJORS on liver stellate cell viability in rat was measured by the MTT assay, and proliferation was measured by the BrdU assay. The mRNA expression of procollagen type $1{\alpha}2$, ${\alpha}-SMA$, TIMP1, and TIMP2 all of which are associated with liver fibrosis, were analyzed by RT-PCR. The inhibitory effect of IJORS on procollagen production in hepatic stellate cell was examined using by enzyme immuno assay(procollagen Type 1 C-Peptide EIA). And after IJORS was orally administered to experimental rats with thioacetamide(TAA)-induced liver fibrosis for 4 weeks, the body weight, liver function test, complete blood and the change of portal pressure were measured. IJORS prevented hepatic stellate cell viability and proliferation in a dose-dependent manner. IJORS reduced the mRNA expression of procollagen type $1{\alpha}2$, ${\alpha}-SMA$ and TIMP1 and the production of procollagen protein. IJORS inhibited the increase of AST, ALT, WBC and portal pressure in rats administered by TAA. IJORS is considered to prevent liver fibrosis by inhibiting the activation of stellate cell and production of procollagen and prevent the progress of liver fibrosis by inhibiting the inflammation of liver tissue complicated in many liver disease.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.1-12
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• 2010

Objective : For this study, mice on mercurial toxication were given mercuric subcutaneous injection to their abdomen factitiously. After delivering Kami- bangpungtongseong-san(KBT) extracts to the mice by oral administration, we observed changes from liver and kidney of mice. Method : The BALB/c mice were distributed into three groups: No treated group(Normal group), Mercuric chloride subcutaneous injection group(Control group), Kami-bangpungtongseong-san-treated group (Sample group). KBT Extracts were delivered orally in 7 days. We observed involution of liver, necrosis of liver and cell plate loss of liver, lipid peroxidation CYP1A1 expression. We observed involution of proximal convoluted tubules, hypertrophy of Bowman's capsule, periodic acid-Schiff(PAS)'s positive reaction of proximal convoluted tubules, heat shock protein(HSP)700's positive reaction in glomerulus. For the charting the results, image analysis was taken. The result of image analysis was verified significance by Sigmaplot 2000(P<0.05). Result : The mice' liver on mercurial toxication were relieved involution of liver, necrosis of liver, and cell plate loss of liver and also declined lipid peroxidation and CYP1A1 expression. The mice' kidney on mercurial toxication were relieved involution of proximal convoluted tubules, hypertrophy of Bowman's capsule and increasing PAS's positive reaction of proximal convoluted tubules. On the other hand it was declined HSP700's positive reaction in glomerulus. Conclusion : According to the result of study, we think that we can expect to the effect of KBT extracts' therapeutic action to tissue injuries of the mice' liver and kidney on acute mercurial toxication.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.22-38
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• 1998

This study was to investigate the hepatoprotective and anticirrhotic effects of Ganyeumilhobang(GIE) on the acute and chronic liver injury induced by various agents. Chronic liver injury induced by dimethylnitrosamine(DMN) ; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. Acute liver njury induced by carbon tetrachloride$(CCl_4)$ and D-galactosamine ; a experimental model for acute liver injury, the administration of $CCl_4$ and the intraperitoneal injection of D-galactosamine in the rat. The development of fibrosis and acute liver injury by the three prescriptions were examined by the chemical analysis of AST, ALT, prothrombin time and hydroxyproline. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by DMN in mice was decreased by the oral administration of GIB. 2. The degree of histological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ decreased by the oral administration of GIB. 3. The increase of senun AST and ALT of mice with acute liver damage induced by $CCl_4$ and D-galactosamine was inhibited by the administration of GIB. 4. The prolongation of prothrombin time(seconds) of mice acute liver damage induced by $CCl_4$ was shortened by the oral administration of GIB. 5. The liver of mice was hepatectomized partial1y after the oral administration of GIB. The mitotic index(% of nuclei), weight of liver, contents of protein, RNA and DNA synthesis of the liver tissue were increased by the oral administration of GIB.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.11-24
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• 2010

Objectives : This study was carried out to investigate the hepatoprotective effects of mixture with Hovenia dulcis Thunb (HDT) and Acer tegmentosum Maxim(ATM) on D-galactosamine-induced liver failure in rats. Methods : The animals were divided into 4 groups: control, with liver failure and no treatment; H1A1, with liver failure and oral treatment with HDT 1 and ATM 1; H1A2, with liver failure and oral treatment with HDT 1 and ATM 2; H1A4, with liver failure and oral treatment with HDT 1 and ATM 4. The animals were treated for 3 weeks and then examinations of change of body weight, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase ($\gamma$-GTP), total cholesterol, triglyceride, total bilirubin, superoxide dismutase (SOD), catalase, histopathologic change, and complete blood count (CBC) were performed. Results : All experimental groups had significantly decreased AST in serum and markedly increased activity of SOD as compared with the control group. H1A1, and H1A4 significantly decreased ALT in serum and H1A4 at 2 weeks was significantly higher on the change of body weight as compared with the control group. In histopathologic change of liver tissue by light microscopy, all experimental groups showed recovery effects of liver cells which were damaged by D-galactosamine. Conclusions : Based upon these results, it could be assumed that a mixture of HDT and ATM has hepatoprotective and antioxidative effects on D-galactosamine-induced liver failure. Therefore, a mixture of HDT and ATM might be utilized as a protective agent in therapy for liver diseases.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.44 no.5
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• pp.451-455
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• 2011

Proximate compositions, fatty acid profiles, and total amino acid compositions of the muscle and liver of Patagonian toothfish Dissostichus eleginoides were studied. Lipid contents of the muscle and liver of the fish were 22.3% and 35.3%, respectively. Protein content was higher in the fish muscle (12.8%) than in the liver (8.7%). Moisture content was also higher in the muscle (63.6%) than in the liver (49.8%). The prominent fatty acids in the total lipids of the fish muscle and liver were 18:1n-9, 16:0, 20:1n-9, 16:1n-7, 22:6n-3 (docosahexaenoic acid, DHA), 18:1n-7, 22:1n-11, 18:0, and 20:5n-3 (eicosapentaenoic acid, EPA). The fish muscle and liver contained approximately 1,000 to 2,500 mg of DHA and 400 to 600 mg of EPA per 100 g of tissue. Therefore, the fish muscle and liver are good sources of n-3 polyunsaturated fatty acids. On the other hand, the total amino acid content of the fish was 11.7 g/100 g muscle and 6.53 g/100 g liver. The prominent total amino acids profiles in the fish muscle and liver were glutamic acid, lysine, aspartic acid, leucine, and alanine, which are similar to those in other fishes.

• Bulletin of the Korean Chemical Society
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• v.32 no.11
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• pp.3967-3972
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• 2011

A whole body physiologically based pharmacokinetic (PBPK) model was applied to investigate absorption, distribution, and physiologic variations on pharmacokinetics of imatinib in human body. Previously published pharmacokinetic data of the drug after intravenous (i.v.) infusion and oral administration were simulated by the PBPK model. Oral dose absorption kinetics were analyzed by adopting a compartmental absorption and transit model in gut section. Tissue/plasma partition coefficients of drug after i.v. infusion were also used for oral administration. Sensitivity analysis of the PBPK model was carried out by taking parameters that were commonly subject to variation in human. Drug concentration in adipose tissue was found to be higher than those in other tissues, suggesting that adipose tissue plays a role as a storage tissue for the drug. Variations of metabolism in liver, body weight, and blood/plasma partition coefficient were found to be important factors affecting the plasma concentration profile of drug in human body.

• Korean Journal of Medicinal Crop Science
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• v.17 no.4
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• pp.243-250
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• 2009

Fifty percent ethanol extract of Lythrum salicaria Linne root (LSR) was tested in vitro on antioxidant activity, and furthermore was investigated on antioxidative and fibrosis protecting activities in $CCL_4$-induced liver fibrosis rat model. Ratio of hepatic GSH/GSSG (reduced glutathione/oxidized glutathione) as bio-parameter of antioxidant level in $CCL_4$ plus LSR-treated rats for 6 weeks significantly increased from 2.8- to 5.7-fold than that of $CCL_4$-treated rats at p < 0.05. Thiobarbituric acid reactive substances (TBARS) contents in $CCL_4$ plus LSR-treated rats ranged from 1.57- to 2.19-fold of normal rats and were lower than those in $CCL_4$ plus silymarin-treated rats ($1.78{\sim}2.46$-fold of normal rats) (p < 0.05). Amounts of hydroxyproline of liver tissue showing the content of total collagen, a parameter of fibrosis, in $CCL_4$ plus LSR-administrated rat livers were $4.9{\sim}8.8{\mu}g$/mg ($-47{\sim}-71%$, compared with that in $CCL_4$-treated rat livers ($16.6{\mu}g$/mg tissue), which were significantly lower than those in $CCL_4$ plus silymarin-administrated rats being $8.4{\sim}11.7{\mu}g$/mg ($-30{\sim}-50%$). This collagen reducing effect of liver tissue in $CCL_4$ plus LSR-treated rats was supported by histological observation using microscopy assay. From the results, we conclude that the root of L. salicaria have efficient antioxidant potential and effective antifibrotic activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1784-1794
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• 2004

To study the effects between Cd inhalation toxicity and methanol extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 0.98㎎/㎥ and mass median diameter(MMD) was 1.78㎛. 3 different dose intraperitoneal injections of methanol extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups applied for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group Ⅲ(p<0.05). The highest lung weight was from inhalation exposure group Ⅲ and the highest liver and kidney weight were from inhalation exposure group Ⅱ(p<0.05). The lowest Cd content in lung was 22.77㎍/g from inhalation exposure group Ⅲ(p<0.05). The highest Cd concentration in blood was 11.71㎍/㎗ from inhalation exposure group Ⅰ(p<0.05). Cd concentrations of 14.87㎍/g in liver and 17.91㎍/g in kidney were the highest from inhalation exposure group Ⅰ(p<0.05). The lowest Cd concentration in liver and kidney were 5.71㎍/g and 3.17㎍/g from the control(p<0.05). For weekly Cd concentration in urine, the highest value was 0.48㎍/㎖ from inhalation exposure group Ⅲ of the 3rd week and inhalation exposure group Ⅰ, Ⅱ of the 4th week. For weekly Cd concentration in feces, the highest value was 0.32㎍/g from inhalation exposure group Ⅰ, Ⅱ, Ⅲ. The highest metallothionein concentration in lung was 89.02㎍/g from inhalation exposure group Ⅲ(p<0.05). The highest metallothionein concentrations in liver and kidney were 265.47㎍/g and 214.21㎍/g from inhalation exposure group Ⅲ, respectively(p<0.05). The highest Hct, Hb, and WBC values were from inhalation exposure group Ⅱ and the highest RBC value was from inhalation exposure group Ⅲ(p<0.05). Mostly damaged part in liver tissue was hepatic lobule and the degrees of damage were lessened by the intraperitoneal injection of methanol extract of Radix Achyranthis Bidentatae. Proximal, distal convoluted tubules and glomerulus in kidney tissue were mostly damaged part. Degeneration and swelling were partially observed but the degrees of kidney tissue damage were lessened more or less by the intraperitoneal injection of methanol extract of Radix Achyranthis Bidentatae.

• Toxicological Research
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• v.25 no.2
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• pp.71-78
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• 2009

We investigated the pathogenesis of liver tissue damage during the lipid peroxidation and fibrogenesis with the observation of correlations between the parameters of collagen synthesis (and deposition) and lipid peroxidation in liver fibrosis (cirrhosis) rats. Rats were randomly divided into two groups, normal and $CCl_4$-thiopental sod. intoxicated group. And the one group was treated intragastrically with the mixture of $CCl_4$-thiopental sod. 3 times per week for 3 weeks. The liver tissue and sera were used for the measurement of hydroxyproline (HYP), malonedialdehyde (MDA) and superoxide dismutase (SOD). Biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total-bilirubin and blood urea nitrogen (BUN) were measured. Additionally, the expression of collagen ${\alpha}1$(III) and $\beta$-actin mRNA was observed by RTPCR. The histological change in liver tissue was also observed by Masson's trichrome and H&E staining. Correlation analysis was carried by Spearman's rho method. All biochemical parameters except total-bilirubin were significantly higher in the $CCl_4$-thiopental sod. treated group than that of the normal group (p < 0.01). In the $CCl_4$-thiopental sod. treated group, Hyp as a parameter of collagen synthesis (deposition) and MDA as a metabolite of lipid peroxidation, were significantly elevated by 1.98 and 2.11 times higher than that of the normal group (p < 0.001) respectively. The activity of SOD in the $CCl_4$-thiopental sod. treated group is decreased significantly by 44.8% (p < 0.001). And collagen ${\alpha}1$(III) mRNA was more expressed in the $CCl_4$-thiopental sod. treated group than that of the normal group. However, the expression of $\beta$-actin mRNA is showed similar in both of groups. A good correlation was observed between the content of hyp and MDA concentration (r = 0.70, n = 40) in the two groups. And the correlation between the levels of hyp and SOD (r = -0.71, n = 25) is also reliable. However, no correlation were observed between MDA concentration and SOD (r = -0.40, n = 25) in the two groups. Elevated levels of MDA in $CCl_4$-thiopental sod. treated rats indicated enhancement of lipid peroxidation, which is accompanied by a decrease in SOD activity. Moreover, we could confirm that the parameters of collagen synthesis (and deposition) is in good correlation with the metabolite of lipid peroxidation (MDA) and the lipid peroxidation antagonizing enzyme (SOD). Hence, we propose that (1) lipid peroxidation and collagen synthesis (and deposition) could be enhanced by intragastrically application of $CCl_4$-thiopental sod. during a short terms. And (2) the intoxication of $CCl_4$-thiopental sod. could be used for monitoring of lipid peroxidation and collagen synthesis (and deposition) for test of antioxidant and antifibrotic agent.