• Journal of Ginseng Research
• /
• v.13 no.1
• /
• pp.5-7
• /
• 1989

The objective of this study was to investigate the preventive effect of ginseng on acetaldehyde-induced acute toxicity in mice . Compared to the control group, treatment with acetaldehyde inhibited the hepatic cytosolic xanthine oxidise activity with increase in dose. The inhibition of enzyme activity was not changed after dialysis. Pretreatment with ginseng butanol fraction prevented the inhibition of enzyme activity by acetaldehyde. In conjunction with the our previous results (Yakhak Hoeji, 29, 18 (1985)), these results suggest that the most likely mechanism for the observed preventive effects of ginseng against the acetaldehyde-induced acute toxicity may be the decrease hepatic acetaldehyde level.

• Molecular & Cellular Toxicology
• /
• v.1 no.3
• /
• pp.164-171
• /
• 2005

Toxicological studies have an object of detecting adverse effects of a chemical on an organism based on observed toxicity marker (i.e., serum biochemical markers and chemical-specific gene expression) or phenotypic outcome. To date, most toxicogenomic studies concentrated on hepatic toxicity. cDNA microarray analysis enable discrimination of the responses in animals exposed to different classes of hepatotoxicants. In an effort to further characterize the mechanisms of 2, 3, 7, 8,-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin)-mediated toxicity, comprehensive temporal-responsive microarray analyses were performed on hepatic tissue from Sprague-Dawley rats treated with TCDD. Hepatic gene expression profiles were monitored using custom DNA chip containing 490 cDNA clones related with toxicology. Gene expression analysis identified 26 features which exhibited a significant change. In this study, we observed that the genes related with oxidative stress in rats exposed to Dioxin, such as CYPIIA3 and glutathione S-transferase, were up-regulated at 24hr after exposure. In this study, we carried out to discover novel evidence for previously unknown gene expression patterns related to mechanism of hepatic toxicity in rats exposed to dioxin, and to elucidate the effects of dioxin on the gene expression after exposure to dioxin.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.23 no.3
• /
• pp.380-386
• /
• 1994

The behavior of glycogen and histological changes of hepatic tissues in the liver of rats, aged 6 to 7 weeks, fed 18% casein diet under control, gramoxone and gramoxone + vitamin C(Vt. C) diets has been investigated in a comined histropathological and histochemical studies. Cloudy swelling and fat changes of hepatic cells were observed in the gramoxone group with the duration of feeding time. Fat changes of hepatic cells were observed more obviously than cloudy welling, especially in the hepatic cells of periportal area. The number of Kupffer's cells increased signifciantly in the gramoxone group fed for 4weeks. The cloudy swelling and fat changes decreased obviously in the gramxone + Vt. C group. Glycogen content of heaptic cells tended to increase slightly in the gramoxone group as compared with the control group . moreover, glycogen depositons were higher in the hepatic cells where fat changes were obvious. It seems to be that Vt.C alleviating effects on the gramoxone toxicity in the patterns of glycogen distribution and histological structure of heaptic tissues.

• Journal of Environmental Science International
• /
• v.6 no.1
• /
• pp.53-60
• /
• 1997

The toxicity of purified ricln from Ricinus communis to rats was examined by histological and histochemical methods. Sprague-Dawley rats were injected intraperitoneally with 75$\mu\textrm{g}$/kg body weight of ricin and were sacrified at itntervals of 6, 24, 48 and 120 hours after injectoon. The major morphological changes, such as cloudy swelling, hydropic degeneration, necrosis, fatty change, blood congestion, increase of Kupffer cells in number and extension of sinusoids, were obvious in the liver of experimental group. These morphological changes of hepatic cells were mainly observed in both the periportal and midlobular region of hepatic lobule. The extension of sinusoids was obvious in the controlobular region. And glycogen dlstrlbution of hepatic cells tended to decrease in the same region showing morphlogical changes as compared with the control group.

• Toxicological Research
• /
• v.6 no.1
• /
• pp.51-59
• /
• 1990

Effects of altering hepatic mixed-function oxidase (MFO) enzyme activities on the metabolism and acute toxicity of parathio were investigated in adult female rats. In vitro hepatic metabolism of parathion to paraoxon was increased by phenobarbital pretreatment (50 mg/kg/day, ip, for 4 consecutive days) and SKF 525-A (50 mg/kg, ip, 1 hr prior to sacrifice) decreased paraoxon formation indicating that phenobarbital induces that form(s) of cytochrome P-450 catalyzing conversion of parathion to paraoxon. Degradation of paraoxon to p-nitrophenol was increased by phenobarbital pretreatment, but not affected by SKF 525-A suggesting that MFO activities play only a minor role in the detoxification of the active metabolite of this insecticide. The phenobarbital-induced increase in paraoxon formation was partially antagonized by SKF 525-A. Significant activity for both parathion activation and paraoxon degradation was also observed in the lung preparation, however, this extrahepatic parathion and paraoxon metabolizing activity was not induced by phenobarbital or inhibited by SKF 525-A pretreatment. Phenobarbital pretreatment increased paraoxon level in livers of rats when measured 3 hr following parathion injection (2 mg/kg, ip). SKF 525-A did not alter parathion or paraoxon levels in brain, blood and liver. Phenobarbital pretreatment decreased the toxicity of parathion (4mg/kg, ip) or paraoxon (1.5 mg/kg, ip) as determined by decreases in lethality and inhibition of brain and lung acetylcholinesterases. An additional SKF 525-A treatment failed to decrease the protective effects of phenobarbital against parathion or paraoxon toxicity. These results suggest that some unknown factors other than hepatic MFO induction are involved in the protective action of phenobarbital against parathion and paraoxon toxicity.

• Molecules and Cells
• /
• v.46 no.8
• /
• pp.496-512
• /
• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• The Journal of Korean Medicine
• /
• v.31 no.5
• /
• pp.90-102
• /
• 2010

Objectives: This study was investigated the protective effect of Spatholobi Caulis water extract against cadmium (CdCl2, Cd)-induced hepatic toxicity in rats. Methods: To induce acute hepatic toxicity, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. Then, the rats received either a vehicle or silymarin (100 mg/kg) or Spatholobi Caulis water extract (30, 50 mg/kg/day) for 3 days, and were exposed to a single injection of Cd 24 h after the last Spatholobi Caulis/vehicle treatment. Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with Spatholobi Caulis reduced ALT, AST and LDH. Cd-intoxicated liver damage was significantly inhibited by treatment of Spatholobi Caulis 30 and 50 mg/kg at histopathological observations in the present study. Conclusions: These results can be considered as direct evidence that Spatholobi Caulis has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Spatholobi Caulis 30 mg/kg shows similar effects to that of silymarin 100 mg/kg, and more favorable hepatoprotective effects were observed in Spatholobi Caulis 50 mg/kg as compared with silymarin 100 mg/kg against Cd-intoxicated hepatopathies in the present study.

• Environmental Analysis Health and Toxicology
• /
• v.10 no.3_4
• /
• pp.1-5
• /
• 1995

The general toxicological study of new platinum(II) compounds, KHPC-002, KHPC-005 and KHPC-006 were investigated in rats. The effects of these Pt(II) complexes on renal, hematopoietic and hepatic system in rats showed lower toxicity compared with cisplatin. In the consideration of the maximal dose of these Pt(II) complexes using in this experiment is 4-8 times higher than cisplatin, these novel compounds will have the less general toxicity in vivo.

• Journal of fish pathology
• /
• v.36 no.2
• /
• pp.415-422
• /
• 2023

In veterinary medicine for mammals, studies are being conducted to confirm the effects of antioxidants using pathological toxicity model studies, and are also used to confirm the effect of mitigating liver or kidney toxicity of specific substances. It was considered necessary to study such a toxicity model for domestic farmed fish, so thioacetamide (TAA), a toxic substance that causes tissue damage by mitochondrial dysfunction, was injected into rainbow trout (Oncorhynchus mykiss), a major farmed freshwater fish species in Korea. The experiment was conducted with 40 rainbow trout (Oncorhynchus mykiss) weighting 53 ± 0.6 g divided into two groups. Thioacetamide(TAA) 300mg/kg of body weight was intraperitoneally injected into rainbow trout and samples were taken 1, 3, 5, 7 days after peritoneal injection. As a result, in serum biochemical analysis, AST levels related to liver function decreased 3 and 5 days after intraperitoneal injection and increased after 7 days, and ALT levels also increased after 7 days. In addition, creatinine related to renal malfunction increased 3 and 5 days after TAA injection. In histopathological analysis, pericholangitis and local lymphocyte infiltration were observed in the liver from 1 day after intraperitoneal injection of TAA, and hepatic parenchymal cell necrosis was also observed from 3 days after intraperitoneal injection. Hyaline droplet in renal tubular epithelial cell was observed from 1 day after TAA injection, and acute tubular damage such as tubular epithelial cell necrosis appeared from 3 days after TAA injection. Accordingly, it is thought that it will be able to contribute to studies that require a toxicity model.

• Preventive Nutrition and Food Science
• /
• v.3 no.1
• /
• pp.62-66
• /
• 1998

The effect of dietary capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) on drug-metabolizing enzyme activities was investigated in mice. Male ICR mice were divided into 4 groups and fed diets containing 0, 5, 20, 100 ppm CAP for 4 seeks. Hepatic drug-metabolizing enzyme activities and serum alanine aminotransferase and aspartate transaminease activities were measured. There was no difference in hepatic alanine aminotransferse and aspartate transaminase activities among the groups. Hepatic microsomal cytochrome P450 in CAP fed groups, but p-nitrophenol hydroxylase and the cytosolic acitivity of glutathione S-transferase activities were decreased in the dietary CAP supplemetned groups compared to the control. These results suggest that the dietary CAP at a low dose differentially modulates drug-metabolizing enzyme acitvities without causing hepatic toxicity.