• Journal of fish pathology
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• v.30 no.2
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• pp.115-134
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• 2017

A total number of 668 apparently healthy fish were obtained from farm to study the effect of two heavy metals (Copper and Mercury) on histopathology of liver, kidney, spleen, gills and muscles also residues in muscles. The $LC_{50}$/96 hr. of Cu and Hg were estimated and fish exposed to 1/2 $LC_{50}$ for 7 days and for 1/10 $LC_{50}$ for 8 weeks from each product separately. Histopathological findings in acute and chronic mercuric chloride toxicity revealed degeneration and necrosis in the glomeruli, interstitium tissue and epithelium lining renal tubules. The tubular epithelium became necrotic at several places. Eosinophilic hyaline droplets is exist in the cytoplasm of the necrosed cells. Degenerative changes and hyperactivity in melanomachrophage center was seen in the spleen together with some necrotic areas. Necrosis and aggregation of melanomachrophage were seen in the hepatic cells, Hepatic cells showed vacuolar degeneration in the hepatic cells. Gills showed loss in the lamellae of the filaments associated with edema, inflammatory cells infiltration and haemorrhages in the arch. The sarcoplasm of the bundles of the skeletal muscle showed granular degeneration and focal inflammatory cells infiltration between the hyalinized bundles. Mercury residues obtained from these studies in the acute toxicity were 0.22 ppm/gm in the 2nd day, 0.411 ppm/gm in the $5^{th}$ day ended with 0.96 ppm/gm in the $7^{th}$ day. In chronic toxicity it was 1.1320, 1.7140, 2.3620 and 3.5640 ppm/gm respectively from the $2^{nd}$ to the $8^{th}$ week of exposure. In acute and chronic copper toxicity, there was degenerative changes in renal tubules. Melanophores aggregation in the wall of the blood vessels of the spleen and depletion of some of the melanophores in the melanomachrophage were seen together with necrosis in some areas. Congested Mvs (Micro vessels) and vacuolation of hepatocytes were observed. Some areas of hemorrhage and melanophores vacuolar degeneration in the liver were seen. There was mitosis in some areas with displesia of hepatopancreatic cells and eosinophilic granular cells aggregation. Zymogen granules disappeared and there were dyplastic hepatocytes. Congestion in the blood vessels of the gill filaments, associated with massive number of granular eosinophilic cells infiltration were seen in the base of the filaments. There were sever vacuolization and hyalinization in the skeletal muscle bundles. Detection of residues of copper sulfate revealed increase of the amount of copper measured in ppm/gm comparing to the normal control starting from 0.60 ppm/g in the $2^{nd}$ day, 0.67 ppm/g in the $5^{th}$ day and 0.67 ppm/g in the $7^{th}$ day. Result obtained in chronic copper sulfate toxicity revealed gradual increase of the amount of copper which ranged from 0.18 ppm/g at the $2^{nd}$ week to 0.21 ppm/g in the $8^{th}$ week of exposure.

• Applied Microscopy
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• v.26 no.1
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• pp.1-9
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• 1996

This paper aims to probe the effect of SQ in the rat liver which pretreated with CP was examined by transmission electron microscope. In the A group, the difference between the normal and the treated groups were not detected at 24 hours, but the few mitochondria were expanded at the 72 hours. In the B group, the cisternae of rough-surfaced endoplasmic reticulum were partially destructed and attached ribosomes were remarkably decreased at 24 hours. A number of the mitochondria were dilated and increased in number, the filamentous materials also detected at 72 hours. These results suggest that SQ is not only concerned with construction of the membrane of the cell organelles but also decreased the cellular toxicity in the hepatic cells.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.101.1-101.1
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• 2003

The therapeutic goal in liver fibrosis is to reverse fibrosis and selective clearance of activated hepatic stellate cells (HSCs), which playa central role in liver fibrogenesis, by apoptosis might be essential during resolution of fibrosis. Past several years we screened for natural products which mediate apoptosis in activated HSCs, and among the candidates honokiol, isolated from Magnoliae Cortex, was found to induce apoptotic death in activated rat HSCs in a dose- and time-dependent manner at the concentration between 12.5 microM and 50 microM. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7527-7532
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• 2014

Saussurea involucrata is a Mongolian medicinal plant well known for its effects in promoting blood circulation, and anti-inflammation and analgesic functions. Earlier studies reported that Saussurea involucrata has anticancer activity. The purpose of this study was to confirm the anticancer activity of an ethanol extract of Saussurea involucrata against hepatic cancer and elucidate its mechanisms of action. Hepatocellular carcinoma cells were tested in vitro for cytotoxicity, AO/EB staining for apoptotic cells, apoptotic DNA fragmentation and cell cycle distribution in response to Saussurea involucrata extract (SIE). The mRNA expression of caspase-3,-9 and Cdk2 and protein expression of caspase-3,-9, PARP, XIAP, Cdk2 and p21 were analyzed through real time PCR and Western blotting. Treatment with SIE inhibited HepG2 cell proliferation dose- and time-dependently, but SIE only exerted a modest cytotoxic effect on a viability of Chang human liver cells. Cells exposed to SIE showed typical hallmarks of apoptotic cell death. Cell cycle analysis revealed that SIE caused G1-phase arrest in HepG2 cells. In conclusion, Saussurea involucrata ethanol extract has potential cytotoxic and apoptotic effects on human hepatocellular carcinoma cells. Its mechanism of action might be associated with the inhibition of DNA synthesis, cell cycle (G1) arrest and apoptosis induction through up-regulation of the protein expressions of caspase-3,-9 a nd p21, degradation of PARP and down-regulation of the protein expression of Cdk2 and XIAP.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.277-287
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• 2004

Objective : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might playa major role. Therefore, many efforts have been made to regulate oxygen free radicals for treating diabetes and its complications. Because Jindangwon has been known to be effective in treatment of diabetes, the methanol extract of Jindangwon was tested for its effectiveness in reducing the oxidative stress induced by Streptozotocin. Methods : Jindangwon was washed, dried in the shade and crushed. The crushed Jindangwon was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24 hours. The extract was filtered and evaporated under reduced pressure using a rotary evaporator to yield 30.6 g. Jindangwon extract was oral-administered to the diabetic rats induced by streptozotocin 50 mg per 1 kg of body weight for 15 days. The efficacy of the Jindangwon extract was examined with regard to the enzymatic pathways involved in the oxygen free radical production and the glutathione balance. Results : he effects of the methanol extract of Jindangwon in streptozotocin-induced diabetics rats with regard to body weight, blood glucose level, hepatic lipid peroxide level, hepatic xanthine oxidase activity and type conversion rate, hepatic glutathione level, hepatic glutathione peroxidase activity, hepatic glutathione reductase activity, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were favorable enough to suggest that it is a cure for diabetes and its complications. Conclusions :These results support Jindangwon as an effective reducing agent for oxidative stress in the tissues and organs by regulating the production of oxygen free radicals. Jindangwon, in particular, shows promising results for its use as a cure, or preventative medicine for diabetes and its complications by reducing oxidative stress in beta-cells of the pancreas.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.3
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• pp.113-119
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• 2011

This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.115.2-116
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• 2000

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.306-316
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• 2009

Objectives : This study was performed to investigate the anti-fibrogenic effect of Curcumae Longae Radix on human hepatic stellate cells. Materials and Methods: Hepatic stellate cells (LX-2) were treated with various concentrations of Curcumae Longae Radix extract for 24, 48, and 72 hours. It was extracted with distilled water. After the treatment, cell viability, proliferation, cell cycle analysis, procollagen levels and the mRNA of the ASMA, TIMPl, TIMP2, MMP2, collagen type la, PDGF-receptor-beta and TGF-beta were measured by using MTT assay, BrdU assay, RT-PCR, and procollagen type 1 C-peptide EIA kit. Results : The viability of HSCs decreased in the 48 hours group, and proliferation of HSCs decreased as the concentration increased. In the cell cycle analysis, Curcumae Longae Radix decreased the ratio of M phase, and increased the ratio of apoptosis, G0/G1 and S phase. In the RT-PCR, the mRNA expression of the collagen type la and ASMA decreased with the Curcumae Longae Radix treatment. The production of procollagen by the HSCs was decreased by the treatment of Curcumae Longae Radix with high dose. Conclusion : These results suggest that Curcumae Longae Radix is helpful in the treatment of liver fibrosis as well as liver cirrhosis.