• Journal of Microbiology and Biotechnology
• /
• v.10 no.3
• /
• pp.375-380
• /
• 2000

The preliminary screening of several cyanobacteria, using mice bioassay, reveale the production of a hepatotoxin by the cyanobacterium Scytonema sp. strain BT 23 isolated from soil. An intraperitoneal injection of the crude toxin (LD50 56 mg/kg body wt) from this strain caused the death of the mice within 40 min, and the anmals showed slinical signs of mice within 40 min, and the animals showed clinical signs of hepatotoxicity. The toxin was purified and partially characterized. The active fraction appears to be nonpolar in nature and shows absorption peaks at 240 and 285 nm. The purified toxin had an LD50 of TEX>$100<\mu\textrm{g}/kg$ body wt and the test mice died within 40 min of toxin administration. The toxin-treated mice showed a 1.65-fold increase in liver weight at 40 min and the liver color chnged to dark red due to intrahepatic hemorrhage and pooling of blood. Furthermore, the administration of the toxin to test mice induced a 2.58, 2.63, and 2.30-fold increse in the activity of the serum enzymes alanine aminotransferase, lactate dehydrogenase, and alkaline phosphatase, respectively. Further experiments with the 14C-labeled toxin revealed a maximum accumulation of the toxin in the liver. The clinical symptoms in the mice were similar to those produced by microcystin-L.R. These results suggest that hepatotoxins may also be produced in non bloom-forming planktonic cyanobacteria.

• Journal of Microbiology and Biotechnology
• /
• v.9 no.1
• /
• pp.9-21
• /
• 1999

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.148-148
• /
• 2002

This study is to characterize the microscopical and ultrastructural changes in chronic exposure of Microcystin-LR (MCLR), a cyclic heptapeptide hepatotoxin, comparing to those in acute lethal toxicity. Female ICR mice were injected intraperitoneally with 10, 20, 30,$\mu\textrm{g}$/kg of MCLR every 3 day for 27 days.(omitted)

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.214.1-214.1
• /
• 2003

Metabonomic analysis using Liquid Chromatography-Mass Spectrometry (LC-MS) was employed to test the feasibility to predict chemical-induced toxicity. Time-dependent metabolic variations were evaluated in rats treated with the model hepatotoxin, ${\alpha}$- naphthylisothiocyanate (ANIT). Urine samples of ANIT treated group and control group were collected up to 7 days postdose. Urine samples were analyzed by gradient HPLC combined with electrospray mass spectrometry. The chromatographic results were data-reduced and analyzed using principal component analysis to show the time dependent biochemical variations induced by ANIT toxicity. (omitted)

• Korean Journal of Microbiology
• /
• v.47 no.3
• /
• pp.268-274
• /
• 2011

Anabaena (Cyanobacteria, Nostocales) are important for water quality controls, because they are often responsible for freshwater green tides; moreover, some species are reported to produce hepatotoxin. In this study, we sequenced RNA polymerase beta subunit (rpoB) gene of Anabaena, and evaluated their sequences for the potential use of a molecular taxonomic marker in this taxon. Anabaena rpoB showed low DNA similarity and high genetic divergences when compared those of 16S rRNA, and the molecular differences were statistically significant (Student t-test, p<0.01). Parsimony analyses showed the rpoB gene evolves 4.8-fold faster than 16S rRNA. In addition, phylogeny of the rpoB gene separated each Anabaena strain more clearly compared with a 16S rRNA tree. These results suggest that the rpoB gene is a useful marker for the molecular phylogenetics and the species discrimination of Anabaena.

• Molecular & Cellular Toxicology
• /
• v.2 no.2
• /
• pp.120-125
• /
• 2006

Phenytoin is an anti-epileptic. It works by slowing down impulses in the brain that cause seizures. The recent microarray technology enables us to understand possible mechanisms of genes related to compounds which have toxicity in biological system. We have studied that the effect of a compound related to hepatotoxin in vitro system using a rat whole genome microarray. In this study, we have used a rat liver epithelial cell line WB-F344 and phenytoin as a hepatotoxin. WB-F344 was treated with phenytoin for 1 to 24 hours. Total RNA was isolated at times 1, 6 and 24h following treatment of phenytoin, and hybridized to the microarray containing about 22,000 rat genes. After analysis with clustering methods, we have identified a total of 1,455 differentially expressed genes during the time course. Interestingly, about 1,049 genes exhibited differential expression pattern in response to phenytoin in early time. Therefore, the identification of genes associated with phenytoin in early response may give important insights into various toxicogenomic studies in vitro system.

• Toxicological Research
• /
• v.22 no.4
• /
• pp.375-380
• /
• 2006

Microcystin-LR (MC-LR) is a cyanobacterial hepatotoxin mainly produced by Microcystis aeruginosa. The current study examined the effects of a single intraperitoneal dose of MC-LR in rats. Female Sprague-Dawley rats were intraperitoneally injected with MC-LR ($100{\mu}g/kg$ body weight) and they were sacrificed at 0, 20, 40, 80, 160 min, or 12 h after injection. Clinically, animals showed lethargy and had ruffled hair beginning at 40 min post injection. In the gross findings, liver was enlarged and its color was changed into dark red beginning at 40 min post injection. Microscopically, dissociation of centrilobular hepatocytes and hemorrhage was observed in the hepatic central legions and such pathological changes were then extended to the portal regions of liver by time course manner. Interestingly at 80 min after MC-LR injection, the entrapped eosinophilic materials that may be necrotic fragments of dissociated hepatocytes were found in the capillaries of lung and renal glomerulus. Ultrastructurally, microvilli of the hepatocytes were disrupted or lost at all time points. Furthermore, the Disse space and gap junctions were widened beginning at 40 min post injection. These results suggest that liver is the major target organ of MC-LR and isolated hepatocytes by the effects of such hepatotoxin may secondarily reduce the physiological function of lung and kidney.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.22 no.5
• /
• pp.1210-1214
• /
• 2008

The purpose of this study is to investigate the effect of water extract from Artemisiae Argi Folium (WAAF) on hepatotoxicity caused by acetaminophen (AAP) and acetaldehyde which are regarded as hepatotoxin. Artemisiae Argi Folium was known to have the antibacterial, immune-enhancing, and anticoagulative properties. In Korean Medicine, Artemisiae Argi Folium is supposed to be related with 'liver meridian' according to traditional medical theory. AAP and acetaldehyde reduce the intracellular production of hydrogen peroxide ($H_2O_2$) and nitric oxide (NO) production of human hepatocyte HepG2. The intracellular production of hydrogen peroxide ($H_2O_2$) was measured by dihydrorhodamine 123 (DHR) assay. NO production was measured with Griess test. WAAF increased the production of $H_2O_2$ and NO reduced by AAP and acetaldehyde in HepG2 cells. Therefore, It could be suggested that WAAF has the hepatoprotective activity against AAP and acetaldehyde.

• Natural Product Sciences
• /
• v.12 no.1
• /
• pp.8-13
• /
• 2006

The present study was carried out to investigate the hepatoprotective effect of the extract of Pterocarpus santalinus Linn on acute hepatotoxicity induced in Wistar albino rats by a single dose of Galactosamine (400 mg/kg). Suspensions of methanolic extract of heartwood of P. santalinus (200 and 400 mg/kg) in 0.3% Carboxy Methyl Cellulose (CMC) were administered p.o. to experimental animals and hepatoprotective activity was monitored by estimating aspartate amino transferase (ASAT, GOT), alanine amino transferase (ALAT, GPT), alkaline phosphatase (ALP), total bilirubin (TB), lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TGL), albumin, total protein (TP) levels. The methanolic extract significantly reduced the elevation of serum transaminases and alterations of biochemical parameters induced by hepatotoxin, and alleviated the degree of liver damage. The results were supported by histopathological studies of liver samples showing regeneration of hepatocytes in treated animals. Silymarin (25 mg/kg), a known hepatoprotective drug was used for comparison. Based on the results obtained, it can be concluded that P. santalinus exerts hepatoprotective activity and may serve as a useful adjuvant in several clinical conditions associated with liver damage.

• Biomolecules & Therapeutics
• /
• v.10 no.1
• /
• pp.12-18
• /
• 2002

Silymarin and curcumin have been used for supportive treatment of liver disease of difffrent etiology due to their hepatoprotective activities. The present study was carried out to investigate the hepatoprotective efffcts of silymarin and/or curcuma extract against hepatotoxins induced liver injury. To investigate hepatoprotective effects, the silymarin and/or curcuma extract were pre-treated orally to experimental animals. And thereafter a single dose of hepatotoxin, carbon tetrachloride ($CCl_4$) and acetaminophen were administered through oral or intraperitoneal route, respectively. Chronic liver damage was induced by subcutaneous injection of $CCl_4$ for 3 weeks (2 times/week). Hepatoprotective and therapeutic effects were monitored by estimating serurn ALT and AST levels and by measuring hepatic glutathione (GSH) and malondialdehyde (MDA)levels. Collagen type 1 was detected with irnrnunostaining to assess fibrosis. The results showed that the mix-ture of silymarin and curcuma extract significantly reduced serum biochemistry levels and MDA levels com-pared with those of control group in both acute and chronic animal models. In antifibrotic effect, the relative hepatic collagen content was significantly decreased by silymarin and/or curcuma extract treatment. It was concluded that the complex of silymarin and curcuma extract have a both hepatoprotective and therapeutic effect synergically in rat liver injury induced by heptotoxins.