• Toxicological Research
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• v.22 no.2
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• Journal of Nutrition and Health
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• v.5 no.3
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• pp.127-133
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• 1972

This study was designed to observe the effect of ethanol extracts from fish flour on the nucleic acid metabolism in rats. Young rats, weighing 75-85g were used as the experimental animals and diet used were 8 kinds; diet supplemented with 10% fish flour, diets which were supplemented with the extracts and or remainders of fish flour after extracting by either 76% or 96% ethanol to the rice diet, respectively, and diet supplemented with 6% casein. After feeding corresponding diet for 40 days, RNA and DNA contents, and DNase activities in the liver, kidney and braid were determined. The results obtaioed from this study are summarized as follows: 1. The RNA contents of the ethanol-treatment groups are, in the liver and kidney, similar to, and in the brain, generally higher than, that of the control group. 2. The DNA contents of each organ show no difference between ethanol-treatment groups and control group, but in the liver, of ethanol extrat groups are lower than casein group. 3. the DNase activity of each organ in the ethanol-treatmeut groups, is generally lower than the control group. The above results indicate that ethanol extracts from fish flour have influence on the nucleic acid metabolism.

• BMB Reports
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• v.45 no.7
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• pp.396-401
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• 2012

Overnutrition is one of the major causes of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by an accumulation of lipids (triglycerides) in hepatocytes and is often accompanied by high plasma levels of free fatty acids (FFA). In this study, we compared the energy metabolism in acute steatotic and non-steatotic primary mouse hepatocytes. Acute steatosis was induced by pre-incubation with high concentrations of oleate and palmitate. Labeling experiments were conducted using [$U-^{13}C_5$,$U-^{15}N_2$] glutamine. Metabolite concentrations and mass isotopomer distributions of intracellular metabolites were measured and applied for metabolic flux estimation using transient $^{13}C$ metabolic flux analysis. FFAs were efficiently taken up and almost completely incorporated into triglycerides (TAGs). In spite of high FFA uptake rates and the high synthesis rate of TAGs, central energy metabolism was not significantly changed in acute steatotic cells. Fatty acid ${\beta}$-oxidation does not significantly contribute to the detoxification of FFAs under the applied conditions.

• Molecules and Cells
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• v.42 no.9
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• pp.672-685
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• 2019

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.310-316
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• 2009

Some environmental chemicals have been shown to cause liver-toxicity as the result of bioaccumulation. Particularly, fungicides have been shown to cause varying degrees of hepatictoxicity and to disrupt steroid hormone homeostasis in in vivo models. The principal objective of this study was to evaluate the liver-toxic responses of environmental chemicals-in this case selected fungicides and parasiticides-in order to determine whether or not this agent differentially affected its toxicogenomic activities in hepatic tumor cell lines. To determine the gene expression profiles of 3 fungicides (triadimefon, myclobutanil, vinclozolin) and 1 parasiticide (dibutyl phthalate), we utilized a modified HazChem human array V2. Additionally, in order to observe the differential alterations in its time-dependent activities, we conducted two time (3 hr, 48 hr) exposures to the respective IC20 values of four chemicals. As a result, we analyzed the expression profiles of a total of 1638 genes, and we identified 70 positive significant genes and 144 negative significant genes using four fungicidic and parasiticidic chemicals, using SAM (Significant Analysis of Microarray) methods (q-value<0.5%). These genes were analyzed and identified as being related to apoptosis, stress responses, germ cell development, cofactor metabolism, and lipid metabolism in GO functions and pathways. Additionally, we found 120 genes among those time-dependently differentially expressed genes, using 1-way ANOVA (P-value<0.05). These genes were related to protein metabolism, stress responses, and positive regulation of apoptosis. These data support the conclusion that the four tested chemicals have common toxicogenomic effects and evidence respectively differential expression profiles according to exposure time.

• Advances in environmental research
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• v.5 no.3
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• pp.179-187
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• 2016

This study evaluated some markers of oxidative stress in the organs of African Catfish, Clarias gariepinus from Eleyele River in Oyo State, Nigeria. Clarias gariepinus (250 g-400 g) were collected from Eleyele River (a suspected polluted River) and Clarias gariepinus from a clean fish farm (Durantee fisheries) were used as the control. Levels of Malondialdehyde (index of lipid peroxidation), Glutathione (GSH) and activities of antioxidant enzymes- Superoxide dismutase (SOD), Catalase and Glutathione-S-Transferase (GST) were evaluated in the liver, kidney and gills of the fish. From the results, there were significant (p<0.001) increases in malondialdehyde and GSH levels in the liver, kidney and gills of Clarias gariepinus from Eleyele River compared with control. The activity of GST increased significantly (p<0.05; p<0.001) in the liver and kidney of fish from Eleyele River compared with control. There was a significant decrease (p<0.05; p<0.001) in SOD activity in all the organs of Clarias gariepinus from Eleyele River compared with conrol and also a significant (p<0.001) decrease in catalase activity in the gills and kidney of the fish but catalase activity increased in the liver. Increase in lipid peroxidation and alterations in antioxidant status in Clarias gariepinus from Eleyele River show that the fish were under oxidative stress. These suggest that the River is polluted probably as a result of various wastes frequently discharged into the River. This could pose serious health risks to consumers of water and aquatic organisms from the River.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.11
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• pp.1518-1522
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• 2000

Since the n-6 polyunsaturated fatty acid, docosatetraenoic acid (22:4n-6), is a major functional constituent of avian spermatozoa, the effects of two dietary oils rich in fatty acids which are metabolic precursors of 22:4n-6 on the fatty acid profiles of testicular lipids were investigated during a 39 week period of supplementation from 21 to 60 weeks of age. The effects on liver lipids were determined for comparison. Dietary supplementation of male chickens with Arasco Oil, which provides a large amount of arachidonic acid (20:4n-6), increased the proportion of 20:4n-6 in liver phospholipid by almost 2.5-fold. Although liver phospholipid normally contains very little 22:4n-6, this proportion was significantly increased as a result of Arasco feeding, indicating that the conversion of 20:4n-6 to 22:4n-6 was occurring. The phospholipid of the testis contains much higher proportions of 20:4n-6 and particularly of 22:4n-6 than the liver; supplementation with Arasco Oil significantly increased the proportions of both these polyunsaturates in testis phospholipid but the magnitude of this effect was much lower than that which occurred in the liver. Dietary supplementation with Evening Primrose Oil which contains ${\gamma}-linolenic $ acid (18:3n-6) resulted in significant increases in the proportions of 20:4n-6 and 22:4n-6 in liver phospholipid, although the extent of this increase was less than that produced by the Arasco Oil. By contrast, the feeding of Evening Primrose Oil did not alter the fatty acid composition of phospholipid in the testis. The findings raise the possibility that dietary supplementation with Arasco Oil may modulate the fatty acid profile of avian spermatozoa in a way which could potentially be beneficial for fertility. Moreover, the weights of the testes were almost doubled as a result of supplementation with Arasco Oil or Evening Primrose Oil.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.169-173
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• 2013

Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT ($500{\mu}g/kg$) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1737-1742
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• 2015

Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

• Nutrition Research and Practice
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• v.8 no.1
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• pp.54-58
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• 2014

The liver is vulnerable to alcohol-related injury because it is the primary site of alcohol metabolism. Additionally, a number of potentially dangerous by-products are generated as alcohol is broken down in the liver. However, dietary supplements may prevent or relieve some of alcohol's deleterious effects. Therefore, this study was conducted to evaluate the prophylactic effect of aqueous extract of Sesamum indicum (SI) on ethanol induced toxicity in rats. Male Wistar albino rats were divided into control, ethanol, pre-treatment, simultaneous and post-treatment groups. In the prophylactic experiment, Sesamum indicum, (200 mg/kg body weight) was administered by oral gavage for 28 days; two hours before, simultaneously with or two hours after ethanol exposure. Toxicity was induced by administering 45% ethanol (4.8 g/kg bw) by oral gavage. Lipid peroxidation (TBARS) and reduced glutathione (GSH) levels and catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and gluthathione-S-transferase (GST) activities were then determined in the liver, serum triglyceride (TG) levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were monitored and histological examination was carried out. The results revealed that ethanol administration led to significant elevation of TBARS level while depleting in the level of GSH as well as CAT, GPx, SOD and GST activities. Similarly, TG level and ALT and AST activities were elevated. The SI pre-treated group significantly inhibited TBARS, restored GSH level, enhanced CAT, GPx, SOD and GST activities and significantly decreased the elevated level of serum TG, ALT and AST activities. SI treatment (simultaneously with ethanol) exhibited similar effects to those of the SI pre-treated groups, while the SI post-treated group did not show the same protection as the Pre-treated group. S. indicum possesses antioxidant and hepatoprotective properties, that eliminate the deleterious effects of toxic metabolites of ethanol.