• Archives of Pharmacal Research
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• v.27 no.4
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• pp.422-428
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• 2004

Expressed sequence tags (ESTs) were generated from two 3'-directed CDNA libraries constructed from quiescent and activated rat hepatic stellate cell (HSC) to analyze the expression profiles of active genes in both cells. From quiescent and activated HSC, 694 ESTs and 779 ESTs, respectively, were obtained after excluding those having shorter than 30 bp. Amonq ESTs obtained from quiescent and activated HSC, 68 and 73 kinds of ESTs (186 clones and 236 clones), respectively, appeared more than once, implying that their genes are expressed highly in each cell type. 52 among 73 ESTs appeared only in the activated HSC 47 amonq 68 ESTs only in the normal HSC, and 21 in both cells. The genes of these 52 ESTs were assumed to be expressed more highly in the activated HSC. To confirm the high expression of genes of which the ESTs appeared more than twice in the activated HSC, northern hybridization was carried out with RNAs derived from rat normal and fibrotic liver using each of 18 EST DNAs as probe. 13 ESTs showed more intense bands with RNA isolated from the fibrotic liver than normal liver. From these results, we confirm the positive correlation between abundance of transcript in activated HSCs and the expression level in fibrotic liver, The expression profile of the transcripts serves as an important tool in understanding the biological properties of HSC.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.591-595
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• 1997

An ex vivo assay determining the flavin-containing monooxygenase (FMO) activity in perfused rat liver has been developed by assessing the rate of thiobenzamide S-oxide (TBSO) formation from the infused thiobenzamide (TB). The hepatotoxicity by TB or TBSO was not a critical factor for maintaining the FMO activity for up to 50 min. The FMO activity expressed in nmoles TBSO produced/g liver/min was the same for the recycling and non-recycling perfusion. This implies that reduction of the oxidized TBSO back to the parent compound (TB) is negligible. Hydrolysis of the collected perfusates with either ${\beta}-glucuronidase$ or arylsulfatase did not increase the TBSO level and thus, TBSO does not appear to undergo conjugation either to glucuronide or sulfate esters. Thus, measuring the rate of TB S-oxidation in the isolated perfused liver with 1 mM TB for 50 min provides a useful tool for evaluation of the hepatic FMO activity in the absence of hepatic necrosis and without the interferences caused by further conjugation or back reduction of the TBSO to the parent TB.

• YAKHAK HOEJI
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• v.36 no.1
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• pp.66-72
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• 1992

In order to test relationships between hepatotoxicity and transmethylation, activities of protein methylases and SAM (S-adenosyl-L-methionine)-synthetase were examined in liver tissues of rats treated with $CCl_4$. Also the concentrations of SAM and SAH were measured by HPLC in rat liver. The results are as follows. (1). Activities of protein methylases were not significantly changed in 24 hours after $CCl_4$ treatment. However, in 48 hours, activities of protein methylases were significantly increased in comparison with that of control. (2). Activity of SAM-synthetase was increased steadily in the time course after $CCl_4$ treatment. (3). S-adenosyl-L-methionine concentration of liver tissues in $CCl_4$-treated group was elevated in 24 hours, and then declined thereafter. But the SAH concentration was slightly decreased in the time course after $CCl_4$ treatment. These results indicate that SAM was very actively used in transmethylation reactions of $CCl_4$ damaged rat liver, suggesting the strong relationships between hepatotoxicity and transmethylation phenomena.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.2
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• pp.307-313
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• 2001

Iron excess is known to affect long-term iron accumulation and tissue change such as fibrosis in liver. To determine the changes of expression level of genes associated with fibrosis by short-term iron exposure, we measured liver mRNA levels by reverse transcription polymerase chain reaction (RT-PCR) in rats fed dietary carbonyl iron (3%, wt/wt) for 9 weeks. The results showed that the expression of the collagen (I, III) and transforming growth factor (TGF)-$\beta$I mRNAs was enhanced in high-dose iron treated rat, compared to normal-dose iron treated rat. An electron microscopy study revealed that excess iron caused increase of collagen fibrils in liver. The cell shapes and compositions of hepatocytes and extracellular matrix(ECM) in liver were changed by the iron-treatment. Also, necrosised hepatocytes were broadly seen in ECM. Taken together, we suggest that iron overload affects changes of collagen and TGF-$\beta$I gene expression and these changes are associated with liver fibrogenesis.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.188-191
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• 1995

The Present study was undertaken to indicate the major source of NO by liver cells in vitro. Even at early stages of induction or low LPS concentrations, NO was produced at high rates by LPS(Lipopolysaccharide) on the isolated rat kupffer cells. PMA(phorbol 12-myristate 13-acetate) induced NO formation at low rates in the same cells. IFN-${\gamma}$ (Interferon-${\gamma}$) alone had not induced NO formation but it stimulated the effects of LPS. Calcium ionophore A23187 caused no stimulatory effect. It suggests that LPS has especially strong NO inducer on the kupffer cells and its mechanism is related to those on macrophage in other organs. In other nonparenchymal liver cells, sinusoidal endothelial cells were not stimulated to produce NO either by inducers of aortic endothelium(A23187, ATP and ADP) or by effectors of macrophages(LPS, IFN-${\gamma}$. This results suggest that rat liver kupffer cells appear to be the major source of NO by liver cells in vitro. But in vivo, liver endothelial cells may still be capable of producing NO. Furthermore, kupffer cells may produce factors that facilitate NO production by the endothelial cells.

• YAKHAK HOEJI
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• v.53 no.6
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• pp.314-320
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• 2009

We examined metabolic conversion of cysteine into glutathione (GSH) and taurine in rat liver under oxidative stress. Administration of tert-butylhydroperoxide (t-BHP) into the portal vein of male rats resulted in a rapid elevation of serum sorbitol dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities, which decreased gradually in 24 hr. Hepatic cysteine concentration was reduced in 3 hr, and recovered progressively, reaching a level greater than 200% of the normal value in 24 hr. GSH was increased both in liver and blood at 9 hr after t-BHP challenge, whereas hypotaurine or taurine was not altered. $\gamma$-Glutamylcysteine synthetase (GCS) activity was increased from 9 hr after t-BHP treatment, but protein expression of the GCS-heavy subunit was not changed in liver. Activity or expression of cysteine dioxygenase was not affected by t-BHP treatment. Taken together, these data show that an acute oxidant challenge to the rats may induce upregulation of cysteine availability and GCS activity, resulting in an enhancement of hepatic GSH synthesis, but the increased cysteine level does not stimulate taurine synthesis via cysteine sulfinate pathway. It is indicated that the regulation of GSH and taurine biosynthesis from cysteine is not solely dependent on the cysteine concentration in rat liver under oxidative stress.

• YAKHAK HOEJI
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• v.26 no.4
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• pp.253-256
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• 1982

The organ distribution of mercury was examined in the rat after oral administration of a single dose of red mercuric sulfide (15mg Hg/kg). The concentration of total mercury in the organs and blood after 2, 4, 6, 8, 12, 24 and 72 hours of administration was determined by Quartz Tube Combustion-Gold Amalgamation Method. It was found that the maximal concentration of total mercury was in the kidneys and muscle within 24 hours and in the brain, heart, liver and blood within 48 hours. The descending order of the maximal organ and blood concentration was: kidneys(1.08ppm)>blood> muscle>heart>liver>brain. The accumulation states of total mercury in the rat organs were investigated by continuous administration of red mercuric sulfide (5mg Hg/kg/day) for 15 days. The mercury concentration increased progressively throughout the experimental period and the descending order of the highest level of mercury after 15 days was: kidneys (1.55ppm)>blood>liver. The concentration of alkyl mercury in brain, liver and kidneys also was measured after 7 and 15 days of consecutive administration of red mercuric sulfide (5mg Hg/kg/day). The concentration in the Kidneys and the liver was very low, but was significantly different from control group. The concentration in the brain was extremely low and was not significantly different from control group.

• Herbal Formula Science
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• v.10 no.2
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• pp.127-141
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• 2002

Objectives: Haeganjeon(HGJ) has been used for the treatment of liver disease in traditional medicine. The present study was carried out to evaluate the antioxidant and protective effects of HGJ extract on oxidative damage of hepatocytes by tert-butyl hydroperoxide(t-BHP). Methods: In the linoleic acid water-alcohol system, the levels of lipid peroxide(LPO) were determined by TBA method. The scavenging effect of HGJ on ${\alpha},{\alpha}-diphenyl-{\beta}-picrylhydrazyl$(DPPH) radical was determined according to the method of Hatano. In the Fenton system(ferrous ion reaction with hydrogen peroxide), the levels of hydroxyl radical induced LPO in rat liver homogenate were determined according to the method of TBA. Inhibitory effect of HGJ on superoxide generation was measured by xanthine-xanthine oxidase system. In order to evaluate antioxidative activity of HGJ in the liver cell, cultured normal rat liver cells(Ac2F) were prepared and incubated with or without HGJ. After 18hr, cells placed in DMEM medium without serum, and then incubated with 1mM tert-butyl hydroperoxide(t-BHP) for 2hrs. Viable cells were detected by MTT assay. Conclusions: In the linoleic acid autoxidation system, HGJ extract significantly inhibited the time course of the lipid peroxidation. These effects were similar to those of BHA HGJ extracts showed about 70% scavenging effect on DPPH radical. And HGJ extract inhibited the lipid peroxide formation in rat liver homogenate induced by hydroxyl radical derived from Fenton system. In addition, HGJ extract protected the cell death induced by t-BHP and significantly increased cell viability in the normal rat liver cell. These result indicated that HGJ extract might playa protective role against oxidative hepatic cell injury by means of free radical scavenger.

• Journal of the Korean Society of Food Science and Nutrition
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• v.13 no.4
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• pp.451-458
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• 1984

The effects of branched chain amino acids added to a diet on changes in the body weight with or without liver, moist and dry liver weight, protein, DNA, $^3H-thymidine$ incorporation into DNA, ana mitotic index of regenerating liver were studied in partial hepatectomized rat. Experimental diet was a 14.63% casein diet supplemented with 1.49% L-leucine, 0.90% L-isoleucine and 0.98% L-Valine, and control diet was an 18.0% casein. In both diets, 2.54% nitrogen were included. Rats fed experimental diet were significantly increased body weight with or without liver 7 days, and regenerated weight of dry liver and an index of liver regeneration 5 days after partial hepatectomy. Mitotic index, contents of protein and DNA increased in regenerating liver after partial hepatectomy was higher in experimental diet group. This results suggest that branched chain amino acids have an benefitial effect on whole body as well as liver regeneration after partial hepatectomy in rat.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1362-1373
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• 2004

In studying the specific effects of some drugs, animals under experiments get some stress through laboratory environments, drug injection, and adaptation period. These stimuli do harms on liver function. Nowadays studies on liver intoxication and its protection are under research, but the function of dissolution is rarely under studies. It is widely accepted that Soshiho-tang has function of clearing away low spirits, and that it enables liver bloods to move stronger, and to have calm mind. So I injured rats liver by injectioning CCI₄. And the rats took in Soshiho-tang solution. I made a comparison between the functions before and after rat's liver damage. There are many representative serums used to note an index on liver damage. I used total protein, albumin, ALP, GOT, GPT activity, P450, SOD, Catalase, GST, GR, and GPx. I got the following results. When Soshiho-tang was injected after CCI4 intoxication, total protein and albumin decreased. When Soshiho-tang was injected, ALP decreased, compared with control group. When Soshiho-tang was injected after CCI₄ intoxication, AST and ALT decreased. When Soshiho-tang was injected before CCI₄ intoxication, P450 was restrained. When Soshiho-tang was injected, LPO was all restrained. When Soshiho-tang was injected, SOD, Catalase, GST, GR, and, GPx increased. These results show that blood test reveals that it is good to inject Soshiho-tang after CCI₄ intoxication, but that it is good to inject Soshiho-tang before CCI₄ intoxication in case of P450, LPO, SOD, Catalase, GST, GR, and GPx. It is estimated that the medication period and time of liver damage by CCI₄ have counter results, and that it needs more modified study.