• Environmental Analysis Health and Toxicology
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• 제22권3호
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• pp.227-233
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• 2007

It has been reported that hepatic glutathione (GSH) levels are decreased in diabetic patients, and glucagon increases hepatic efflux of GSH into blood. The signaling pathways responsible for mediating the glucagon effects on GSH efflux, however, are unknown. The signaling pathways involved in the regulation of GSH efflux in response to glucagon and insulin were examined in primary cultured rat hepatocytes. The GSH concentrations in the culture medium were markedly increased by the addition of glucagon, although cellular GSH levels are significantly decreased by glucagon. Insulin was also increased the GSH concentrations in the culture medium, but which is reflected in elevations of both cellular GSH and protein. Treatment of cells with 8-bromo-cAMP or dibutyryl-cAMP also resulted in elevation of the GSH concentrations in the culture medium. Pretreatment with H89, a selective inhibitor of protein kinase A, before glucagon addition markedly attenuated the glucagon effect. These results suggest that glucagon changes GSH homeostasis via elevation of GSH efflux, which may be responsible for decrease in hepatic GSH levels observed in diabetic condition. Furthermore, the present study implicates cAMP and protein kinase A in mediating the effect of glucagon on GSH efflux in primary cultured rat hepatocytes.

• 동의생리병리학회지
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• 제20권6호
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• pp.1658-1663
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• 2006

Panax notoginseng (Buck) F.H chen. root (PNS) is used as a therapeutic agent to stop haemorrhages and a tonic to promote health in Korean and Chinses medicine. The pharmacokinetic profiles of the main PNS are still not accurately investigated. Our preliminary aim is to elucidate the pharmacokinetics features of the PNS in rats. Objective of this study is to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). No has been found to be a modulator of the adhesive interactions between platelet and endothelial cells. Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg pre day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-${\alpha}$ and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an No synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-${\alpha}$ levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-${\alpha}$ production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect like corticosteroid effect.

• BMB Reports
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• 제39권6호
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• pp.677-685
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• 2006

Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be targeted for refolding or degradation to maintain the homeostasis of the ER. Derlin-1 was reportedly implicated in the retro-translocation of misfolded proteins from the ER to the cytosol for degradation. In this report, we showed that Derlin-1 was down-regulated in the endothelial cells derived from human hepatic cavernous hemangioma (CHEC) compared with other tested cells. Electron microscopy analysis showed that ER was aberrantly enlarged in CHEC cells, but not in other tested cells. When overexpressed, Derlin-1 induced the dilated ER to return normal size. This ER dynamic was associated with the activation of unfolded protein response (UPR). In CHEC cells where Derlin-1 was down-regulated, increased expression of the immunoglobulin heavy chain-binding protein (Bip) and UPR-specific splicing of X-box DNA-binding protein 1 (XBP1) mRNA were detected, as compared with that in other tested cells, indicating that UPR was activated. After Derlin-1 overexpression, the extent of UPR activation diminished, as evidenced by decreased expression of Bip, reduced amount of the spliced form of XBP1 ($XBP1_S$), and elevated expression of the unspliced form of XBP1 ($XBP1_U$). Taken together, these findings provide another example of a single protein being able to affect ER dynamic in mammalian cells, and an insight into the possible molecular mechanism(s).

• Applied Microscopy
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• 제29권1호
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• pp.43-56
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• 1999

태생기 간 적혈구형성 중 혈관밖공간의 미성숙 적혈구모세포의 일부는 동굴모세혈관 속공간으로 이주하며, 별큰포식세포에 의해 영향을 받는다. 본 연구에서는 혈관속공간에 이주한 미성숙 적혈구모세포와 별큰포식세포의 관계를 규명하고자 간 적혈구형성의 활성도가 높게 유지되는 태령 제 11주부터 태령 제 20주에 이르는 태아 간과 쥐 태자 간의 연구재료를 대상으로 투과 및 주사전자현미경 관찰을 통해 다음과 같은 결론을 얻었다. 1) 별큰포식세포는 성인 간이나 다른 태령 시기에 비해 비대하였고 많은 세포질돌기들을 갖고 있었다. 이 세포는 부분적으로 세포분열에 의해 증식되고 있었으며 성인 간의 별큰포식세포와 다르게 자가종식을 할 수 있었다. 3) 호산성적혈구모세포에서 탈출된 핵은 별큰포식세포의 속공간쪽과 간세포쪽 세포막에서 포식되었다. 포식된 핵은 주변 부위에 층판이 형성되거나 및 개의 작은 조각으로 파괴되는 등 다양한 소화과정을 보였다. 3) 동굴모세혈관 속공간에서 별큰포식세포는 미성숙적혈구모세포들과 직접으로 접촉하거나, 미성숙 적혈구 모세포들 사이에 별큰포식세포의 긴 세포질돌기가 뻗쳐 있어 골수 적혈구형성에서 관찰되는 적혈구모세포섬과 비슷하였다. 이상의 결과를 종합하면 태아 간 적혈구형성이 왕성한 시기의 별큰포식세포는 적혈구를 포식하는 것 외에도, 세포가 비대해져서 동굴모세혈관을 통한 혈액흐름을 감소시키고, 적혈구모세포섬을 구성하여 태아 간 적혈구형성에서 미성숙 적혈구모세포의 성숙과 관련된 기계적 및 생리학적 기능을 수행한다고 생각된다.

• 대한추나의학회지
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• 제3권1호
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• pp.15-29
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• 2002

Objectives : This experimental study was designed to investigate the effects of Galgunseunggi-tang on the weight of obese rats Induced by high fat diet. Methods : A series of have been conducted in order to measure the effects of the above materials weight. serum and fat cells. The have been performed on; (1) the Increasing amount of body weight; (2) the quantity of total cholesterol, tryglyceride, total lipid, free fatty acid, phospholipid, HDL -cholesterol and LDL -cholesterol in serum; (3) the average size of epididymal fat cells and the area rate of fat drops in hepatic lobule. Results : The results were summarized as follows: 1. It was proved that Galgunseunggi-tang suppressed the increasing amount of body weight. GS II group (supplied 60mg per 100g) showed a significant value. 2. It was proved that Galgunseunggi-tang improved the total cholesterol, HDL -cholesterol In serum. but did not show a significance. 3. It was proved that Galgunseunggi-tang decreased the quantify of free fatty acid, phospholipid, LDL -cholesterol in serum. GS I group (supplied 30mg per 100g) showed a significant value. 4. It was proved that Galgunseunggi-tang decreased the quantity of triglyceride, total lipid in serum, and GS II group showed a significant value. 5. Galgunseunggi-tang decreased the average size of epididymal fat cells and the area rate of fat drops In hepatic lobule, and GS I group showed a significant value. Conclusions : Based on the above result, it is assumed that the clinical application of Galgunseunggi-tang can help the treatment of obesity.

• 대한한의학회지
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• 제29권4호
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• pp.171-179
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• 2008

Objective: Bufonis Venenum is the traditional Korean medicine Chan Su, which is obtained from the skin and parotid venom gland of the toads. It has been used for myocardial diseases, inflammation diseases, pain relief, cancer and others. The main components of BV are cinobufotoxin, cinobufalin, bufalin and others. Of these, bufalin, the major active ingredient of BV, has been reported to induce apoptosis and to possess anti-tumor effects. There was no report of anti-tumor screening of BV on hepatic cancer and which signaling pathway can be involved. In order to examine the effect of BV on hepatic cancer and the related signaling pathway with BV-induced apoptosis, human Hep G2 cells were used. Methods: Analysis of apoptosis was confirmed by MTT assay. BV decreased cell viability in a dose and duration dependent manner. To observe which signaling molecules will be activated by BV, phosphorylation of MAPK (p38, ERK, JNK), caspase 8 and caspase 9 were examined by Western blot analysis. Results: The phosphorylation levels of p38 started to increase at 5 min after addition of 5 ${\mu}g$/ml of BV and sustained to increase until 48 hours. The phosphorylation levels of other MAPK (ERK and JNK), caspase 8 and caspase 9 increased in a time-dependent manner. These imply that BV may activate different signaling pathways, MAPK, caspase 8 and caspase 9. These results propose that BV may induce apoptosis on Hep G2 cells through the activation of MAPK, caspase 8 and caspase 9.

• 동의생리병리학회지
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• 제23권5호
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• pp.1025-1034
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• 2009

This study was carried out to examine the protective effect of Cultured Wild Ginseng(CWG) on the acute and subacute toxicities induced by doxorubicin(Doxo) in mice. Heart and liver weight was decreased following Doxo administration. In contrast, such a decrease was significantly attenuated by CWG administration. The value of serum CPK in Doxo group was increased compared with normal group. But the value of CWG group were decreased significantly compared with the values of Doxo group in the liver of the Doxo group, cloudy swelling of hepatic cells and narrowing of sinusoids were observed. Whereas in the CWG group, well oriented hepatic cell cords and sinusoids were observed. In the testis of the Doxo group, necrotic and degenerative changes of the seminiferous tubules, especially beneath testicular membrane were observed. But those lesions were alleviated in CWG group. Cross sectional area of testis and diameter of semineferous tubule were significantly increased in CWG group compared with Doxo group. Body weight was reduced in Doxo group compared with normal group. In contrast, such a decrease was significantly attenuated by CWG administration atwa5th day. Spermatogenetic cells in seminiferous tubules were necrotic and desquamated and the cellularity of seminiferous epithelia was reduced in Doxo group. But those lesions were attenuated by CWG administration. Cross sectional area of testis and diameter of seminiferous tubule were significantly increased in CWG group compared with Doxo group. In addition, the increase in lipid peroxidation(LPO) in testis was inaddition, the, iout such a increased was significantly inhibited in CWG group. BrdU labelled cells in the seminiferous tubules were remarkably decreased in Doxo group. Whereas the number of seminiferous tubules labelled with BrdU in spermatogonia was increased by CWG administration. The obtained results suggest that CWG has protective effect on doxorubicin-induced toxicity. This effect might be mediated through the supplementation of vital energy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1183-1186
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• 2012

Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

• 대한한방내과학회지
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• 제23권1호
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• pp.57-64
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• 2002

Objective : This study was designed to investigate the anti-oxidative effects of Oldenlandiae Diffusae Herba Water extract (ODHW) on lipid peroxidation by free radicals oxidative hepatic injury. Methods : In order to evaluate anti-oxidative activities of ODHW in the liver cell, cultured normal rat liver cells(Ac2F) were incubated with or without ODHW. After 16 hours to 18 hours of experiment, cells were placed in DMEM medium without serum, and then incubated with 1mM tert-butyl hydro-peroxide(t-BHP) for two hours. Viable cells were detected by MTT assay. The levels of LPO induced by hydroxyl radical derived from H2O2-Fe2+ system in rat liver homogenate were determined by means of TBA. Inhibitory effect of ODHW on superoxide generation was measured by xanthine-xanthine oxidase system. Results : In the linoleic acid autoxidation system, ODHW exhibited antioxidant activity, which inhibited 85% of linoleic acid peroxidation. These effects were similar to those of dl-a-tocopherol. ODHW showed scavenging effects on DPPH radical, inhibited superoxide generation in xanthine-xanthine oxidase system, and also inhibited lipid peroxidation of rat liver tissue with hydroxyl radical derived from $H_2O_2-Fe^{2+}$ system. In addition, ODHW protected the cell death induced by t-BHP and it significantly increased cell viability in a normal rat liver cell(Ac2F)

• 동의생리병리학회지
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• 제24권2호
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• pp.249-257
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• 2010

Crataegii Fructus is commonly used as a improving digestion, removing retention of food, promoting blood circulation and resolving blood stasis agent in East Asia. Cadmium (Cd) is widely distributed in the environment due to its use in industry. An exposure to Cd causes dysuria, polyuria, chest pain, hepatic and renal tubular diseases. The liver is the most important target organ when considering Cd-induced toxicity because Cd primarily accumulates in the liver. This study investigated the protective effect of Crataegii Fructus water extract against cadmium ($CdCl_2$, Cd)-induced liver toxicity in H4IIE cells, a rat hepatocyte-derived cell line and in rats. Cell viability was significantly reduced in Cd-treated H4IIE cells in a time and concentration-dependent manner. However, Crataegii Fructus water extract (CFE) protected the cells from Cd-induced cytotoxicity via inhibition of PARP cleavage. To induce acute toxicity in rats, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. The rats then received either a vehicle or silymarin (as a positive control) or CFE (50, 100 mg/kg/day) for 3 days, and were subsequently exposed to a single injection of Cd. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with CFE reduced ALT, AST and LDH. In histopathological analysis, CFE reduced the hepatic degenerative regions and the number of degenerative hepatocytes. These are considered as direct evidences that Crataegii Fructus has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Crataegii Fructus shows slight lower than that of silymarin in the present study.