• Applied Microscopy
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• v.33 no.1
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• pp.59-78
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• 2003

This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The first group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the second one with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). The third one which had already been injeted with chitosanoligosaccharide (0.5% Solution) aweek before (group Ch7+Cd) was used. In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, enzyme activity in serum, glutathione peroxidase (GSHPx) activity and glutathione reductase (GR) activity were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. As the result of enzyme activity in serum, the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in chitosanoligosaccharide-injected groups Cd+Chi and Chi7+Cd was lower than in group Cd. GSH-Px activity was sharply increased in groups Cd+Chi and Chi7+Cd compared to group Cd. GR activity was conspicuously decreased in groups Cd+Chi and Chi7+Cd compared to group Cd. As the result of light microscopic observation, liver cell necrosis caused by cadmium poisoning was obseved in liver cells. The finding of group Cd+Chi and Chi7+Cd was similar total on of normal groups. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi and Chi7+Cd, mitochondria wiht high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.

• Korean Journal of Pharmacognosy
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• v.28 no.4
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• pp.215-224
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• 1997

Gamijiyu-tang (GJT) described originally in the Dong Eui Bo Gam, a traditional reference for oriental medicine in the Korea, has been clinically used for treatment of chronic liver disease. In order to evaluate scientifcally a hepatoprotective effect of GJT in the liver fibrotic disease, the present study investigated how GJT improves a hepatic function in the dimethylnitrosamine (DMN)-treated rat. DMN treatment caused a significant increase of relative liver weight to the body at 28 days after DMN induction. Administration of with a clinical dose decreased significantly the sAST level $(158.8{\pm}7.76\;IU/L)$ elevated by DMN in jection (p<0.01). A similar phenomenon was also observed at change of both Salt and Salt level in the GJT and/or DMN-treated animal (p<0.01, p<0.05, respectively). A remarkable increase of hydroxyproline was observed by treatment of DMN with comparing to the normal rat $(361.9{\pm}7.35\;vs.\;1278.1{\pm}52.9\;{\mu}g/g\;tissue,\;p<0.01)$. This was significantly reduced by a simultaneous treatment of GJT with DMN for 21 days (p<0.05), but not recovered completely to its normal value. In addition. GJT administration ameliorated conspicuously the DMN-induces histopathological changes of liver such as hemorrhage. Cell necrosis and fibrosis. Tak'en together, results described here demonstrated scientifically in first the medicinal efficacy of GJT by using in vivo animal model, indicating that GJT improves the DMN-induced hepatic injury through reducing an excessive accumulation of collagen and histopathological changes. The decreased collagen content may be a pivotal process for GJT to improve hepatic function in the DMN-induced liver fibrosis. The present study suggests that GJT may be useful for and applicable to the treatment of hepatic fibrosis in chronic liver disease.

• Microbiology and Biotechnology Letters
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• v.2 no.1
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• pp.19-27
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• 1974

Thirty one culture filtrates of Penicillium app. isolated from foodstuffs were submitted for toxicity by use of HeLa cell and ICR-mice. Nine strains among the 31 of Penicillia were cytotoxic to the HeLa cell cultures. Seven strains among the 31 of Penicillia were toxic to the ICR-mice and the pathological findings were the liver injury featured by parenchymal cell necrosis and degeneration. As a mass screening, cytotoxicity test using HeLa cells is feasible method to detect the mycotoxin-producing fungi.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.727-733
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• 1996

2-(Allylthio)pyrazine is effective in selectively suppressing constitutive and inducible expression of cytochrome P450 2E1. The effect of 2-(allylthio)pyrazine against potentiat ed chemical injury was studied in rats. Vitamin-A pretreatment of rats substantially increased carbon tetrachloride hepatotoxicity, as supported by an ~4-fold increase in serum alanine aminotransferase (ALT) activity. Concomitant pretreatment of rats with 2-(allylthio)pyrazine at the daily dose of 200mg/kg resulted in a 76% decrease in vitamin-A-potentiated hepatotoxicity, which supported the possibility that 2-(allylthio)pyrazine protects the liver against chemical-induced hepatic injury by the mechanism associated with Kupffer cell inactivation. Pyridine pretreatment caused substantial enhancement in carbon tetrachloride hepatotoxicity. 2-(Allylthio)pyrazine treatment of rats reduced the pyridine-potentiated toxicity in a dose-dependent manner. Animals treated with both pyridine and 2-(allylthio)pyrazine prior to intoxicating dose of CCl$_4$ resulted in 85% and 47% decreases in pyridine-increased triglycerides and cholesterol levels in the liver. The protective effect of 2-(allylthio)pyrazine on the DNA strand breakage induced by benzenetriol was assessed by measuring the conversion of supercoiled ${\Phi}x$-174 DNA to the open relaxed form. 2-(Allylthio)pyrazine blocked the benzenetriol-induced conversion of supercoiled DNA to open circular form in a dose-dependent manner. The presence of 2-(allylthio)pyrazine at the doses from I to 10mM in the incubation mixture containing 5 ${\mu}$M benzenetriol completely protected benzenetriol-induced DNA strand breakage with the EC50 for the 2-(allylthio)pyrazine blocking being noted as ~220 ${\mu}$M, whereas allyl disulfide exerted protecting effect at relatively high concentrations (i.e. ~850 ${\mu}$M), suggesting that 2-(allylthio)pyrazine effectively scavenges the reactive oxygen species. These results provide evidence that 2-(allylthio)pyrazine blocks vitamin A- or pyridine-potentiated CCl$_4$ hepatotoxicity and that the agent is active in protecting DNA by scavenging the reactive oxygen species.

• Journal of Marine Bioscience and Biotechnology
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• v.13 no.2
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.2
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• pp.185-193
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• 1999

Purpose: Proliferation of bile duct-like structures and fibrosis is a hepatic cellular reaction observed in most forms of human liver disease and in a variety of experimental conditions associated with liver injury. The aim of this study was to investigate the activation of Ito cells and bile duct proliferation in the rat after common bile duct ligation (CBDL). Methods: Hepatic morphological abnormalities were examined in rats whose bile ducts had been irreversibly ligated for 15, 21, 24 and 28 days. The liver was examined by immunohistochemical staining for ${\alpha}$-smooth muscle actin, the known marker of activated Ito cells, and light and electron microscopes. Results: After CBDL, the bile canalicular proliferation and interstitial fibrosis were gradually increased in the periportal areas extended to hepatic sinusoids. Ito cells positive for ${\alpha}$-smooth muscle actin were frequently observed in the periductular space and in perisinusoidal space of Disse. Ito cells and myofibroblasts were gradually increased in the interstitial fibrosis until the 28th day after CBDL. Ito cells and myofibroblasts had microfilaments with dense body at the periphery of the cell. Conclusions: Our results suggest that Ito cells may be fibroblastic or myogenic. It has also been postulated that during the development of hepatic fibrosis, Ito cells become myofibroblasts or fibroblast like cells.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.619-626
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• 1994

The purpose of present study was to examine pharmacological effect of Artemisia Iwayomogi methanol extract(AIME) on biochemical parameters(activities of AST, ALT, LDH, and ALP, contents of total bilirubin, total protein, albumin and A/G ratio in serum and levels of hepatic microsomal lipid peroxide and glucose-6-phosphatase activities) against hepatic injury by carbon tetrachloride($CCl_4$) in rats. Increased AST, ALT and LDH activities by $CCl_4$ were decreased in AIMS treatment group at 48 or 72 hours. Together, increased ALP activity by $CCl_4$ almost returned toward normal value in AIME treatment group at 72 hours. Serum total bilirubin contents increased to 87, 79 and 31% compared with normal group by $CCl_4$ which were decreased to 64, 42 and 26% in AIME treatment group at 24, 48 and 72 hours, respectively. Decreased contents of total protein and albumin, and A/G ratio by $CCl_4$ were recovered in AIME treatment group. Hepatic microsomal lipid peroxide levels(nmol malonic dialdehyde/100mg protein) increased to 140, 95 and 78% compared with normal group by $CCl_4$ which were decreased to 107, 74 and 65% in AIME treatment group at 24, 48 and 72 hours, separately. Hepatic microsomal glucose-6-phosphatase activities decreased to 60, 50 and 53% compared with normal group by $CCl_4$ at 24, 48 and 72 hours, respectively, which were increased at 72 hours in AIME treatment group. In conclusion, AIME enhanced the amelioration process from $CCl_4$-induced lipid peroxidation, degeneration of liver cell, and impairment of protein and bilirubin metabolisms.

• Korean Journal of Oriental Medicine
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• v.8 no.2 s.9
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• pp.95-107
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• 2002

Yukmijihwang-tang(YM) is a noted herbal prescription in Chinese and Korean traditional medicines, and it has been known to reinforce the vital essence and has been widely used for a variety of disease such as stroke, osteoporosis, anti-tumor, and hypothyrodism. Regarding its traditional use, YM has been known to reinforce the Yin (vital essence) of liver and kidney. Also it has been known to reinforce nutrition and biological function in brain. Recently, studies suggested that YM increase antioxidant activities and exert the protective effect against oxidant-induced liver cell injury. We investigated the high-throughput gene expression analysis on the Yukmijihwang-tang administrated in SD rats. Microarray data were validated on a limited number of genes by semiquantitative RT-PCR and Western blot analyses. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes in drug discovery This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with herbal medicine. Total RNA from normal control brain and Yukmijihwang-tang administrated brain were hybridized to microarrays containing 10,000 rat genes. The 52 genes were found to be up-regulated(twice or more) excluding EST gene. The nine genes were found to be down-regulated(twice or more) excluding EST gene. Gene array technology was used to identify for the first time many genes expression pathway analysis that arecell cycle pathway, apoptosis pathway, electron transport chain pathway, cytoplasmic ribosomal protein pathway, fatty acid degradation pathway, and TGF-beta signaling pathway. These differentially expressed genes pathway analysis have not previously been iavestigated in the context of herbal medicine efficacy and represent novel factors for further study of the mechanism of herbal medicine efficacy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6457-6461
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• 2015

MicroRNAs directly and indirectly influence many biological processes such as apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and metastasis. They modulate gene expression at the posttranscriptional level and are associated with progression of liver disease. Hepatocellular carcinoma (HCC) is a cancer which mostly occurs in males. There are many factors affect HCC development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), co-infection, environmental factors including alcohol, aflatoxin consumption and host-related factors such as age, gender immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic infection with the hepatitis B virus is the major factor leading to HCC progression since it causes the liver injury. At present, there are many reports regarding the association of SNPs on miRNAs and the HCC progression. In this research, we investigated the role of miR-149 (rs2292832) and miR-101-1 (rs7536540) with HCC progression in Thai population. The study included 289 Thai subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus infection (CHB) and 95 healthy control subjects. The allele and genotype of rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR assay. Our results revealed no significant association between miR-149 (rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population. However, this research is the first study of miR-149 (rs2292832) and miR-101-1 (rs7536540) in HCC in Thai populations and the results need to be confirmed with a larger population.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.460-465
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• 2013

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.