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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume & Issues
Volume 3, Issue 2 - Dec 1987
Volume 3, Issue 1 - Jun 1987
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CYTOTOXICITY OF D-GALACTOSAMINE ON PRIMARY CULTURES OF ADULT RAT HEPATOCYTES
Yang, K.H. ; Park, Kwan-Ha ; Kim, Byung-Sam ;
Toxicological Research, volume 3, issue 2, 1987, Pages 73~80
Primary cultures of adult rat hepatocytes were used to study the cytotoxicity of D-galactosamine. Hepatocytes were isolated by a collagenase perfusion technique and maintained as monolayers in serum-free medium on collagen-coated culture dishes. Treatment of galactosamine to the culture markedly inhibited the uptake of
-aminoisobutyric acid (AIB) inducible with glucagon and dexamethasone. At0.1 mM of galactosamine, AIB uptake was inhibited significantly when treated for 12 hr. At higher doses (0.25, 0.5 and 1.0mM), a significant inhibition was noticed after 1 hr exposure. Generally the magnitude of the inhibition was related to the dose and treatment time of galactosamine. Treatment of galactosamine also produced a dose- and treatment time-related suppression of the tyrosine aminotransferase (TAT) induction caused by dexamethasone. Meanwhile, uptake of ouabain was not affected by the treatment of galactosamine. The viability of the hepatocytes was decreased only slightly by the treatment of galactosamine; more than 87% of the cells excluded tryphane blue when treated 1 mM galactosamine for 12 hr. Galactosamine induced depressions of AIB uptake and TAT activity were prevented by the simultaneous addition of uridine to the culture. D-Galactosamine, cytotoxicity, hepatocytes culture,
-aminoisobutyric acid uptake, tyrosine aminotransferase.
STUDIES ON THE HEPATOTOXICITY PRODUCED BY INTERACTION OF SEVERAL DRUGS CONTAINING AMINO GROUPS AND NITRITE
Moon, Hwa-Hwey ; Kim, Pu-Young ; Park, Han-Soo ; Choi, Cheol-Hee ;
Toxicological Research, volume 3, issue 2, 1987, Pages 81~88
Hepatotoxicity study of the nitrosamine produced by interaction between drugs containing amino groups and soduim nitrite was conducted. In the in vitro study, interaction of 32mM Promethazine HCL or Oxomemazine HCL with 200mM Sodium nitrite produced N-nitroso dimetylamine (NDMA) at 0.4% or 0.03%, respectively. When sodium nitrite was administered with Promethazine HCL or Oxomemazine HCL, trace of NDMA was detected from the gastric contents. After three days of consecutive administration of sodium nitrite with Promethazine HCL or Oxomemazine HCL, the levels of GOT, GPT and SDH in the serum of treated groups were significant higher than that of control group.
ELIMINATION PATTERNS OF ARTERIAL BLOOD CYANIDE ION IN THIOSULFATE-OXYGEN ADMINISTERED RABBIT
Yoo, Keun-Young ; Lee, Yoon-Seong ; Yun, Dork-Ro ;
Toxicological Research, volume 3, issue 2, 1987, Pages 89~96
To test the efficacies of thiosulfate in cyanide poisoning with or without oxygen, after the administration of sublethal dose of potassium cyanide, serial arterial blood samples were collected during 60 minutes in 15 rabbits. Cyanide ion concentrations were measured by Conway cell microdiffusion method, and arterial oxygen tensions were also observed. Comparison of elimination constants showed that arterial blood cyanide ion concentration decreased most rapidly in the thiosulfate with oxygen-administered group. The elimination of cyanide ion by the action of thiosulfate in acutely poisoned rabbit accelerated probably due to oxygen and elimination pattern seems to occur by first-order elimination kinetics.
EFFECTS OF NOVEL DITHIOL MALONATE DERIVATIVES ON LIVER LIPID PEROXIDATION AND ON MICROSOMAL ELECTRON TRANSPORT SYSTEM
Park, Keun-Hee ; Lee, Jong-Wook ;
Toxicological Research, volume 3, issue 2, 1987, Pages 97~110
The effects of 5 novel hepatotrophic agents, dithiol malonate derivatives (DMDs; DMD1-DMD5), on the liver microsomal lipid peroxidation induced by carbon tetrachloride
and the correlations with the changes of microsomal electron transport system were investigated. All DMDs were found to inhibit the lipid peroxidation induced by
in mice and rats as well in vitro liver microsomal system. Therefore, each DMD seemed to have direct mode of action on liver microsomes to inhibit the lipid peroxidation. As an ex vivo study, the induced lipid peroxidation by
and the changes in electron transport system were determined with liver microsomes obtained from rats chronically treated with DMDs for 7 days. The induced lipid peroxide contents in liver microsomal system were lower in DMD1, DMD2 and DMD3 treated group, but higher in DMD4 and DMD5 group when compared to the control group. Cyt. p.450 contents in the microsomes were decreased by the treatment with DMD1, DMD2 and DMD3, but increased significantly by DMD4 with great extent and by DMD5 with less extent. The cyt. p-450 isozymes induced by treatment of DMD4 and DMD5 were identified as 3-methylcholanthrene (MC) type. The NADPH cyt. -C reductase activities of the microsomes treated with DMD1, DMD2, DMD4 and DMD5 were increased in the range of around 20% to 50%, but decreased with DMD3, All DMDs increased dyt.
content and did not alter NAdH-cyt,
reductase activities in the microsomes. In summary, the 5 novel hepatotrophic agents (DMDs) markedly protected against lipid peroxidation induced by
in vivo and in vitro possibly through the mechanism of direct action on the liver microsomes. The degree of inhibition produced by DMDs on lipid peroxidation induced by
seemed to coincide rather with cyt. p-450 contents than with other components of liver microsomal electron transport system including NADPH-cyt, -C reductase.
EFFECTS OF MAILLARD-TYPE PRODUCTS ON SERUM ENZYMES IN RATS AND ON MUTAGENICITY IN SALMONELLA TYPHIMURIUM
Yang, Kwang-Kyu ; Moon, Ja-Yeong ; Park, Ki-Hyun ;
Toxicological Research, volume 3, issue 2, 1987, Pages 111~119
The Maillard reaction products between amino acids and sugars are used effectively as flavors for processed foods and tobacco. Recently, considerable attention has been focused on the toxicological effects of maillard browned compounds. Therefore, we have tested the safety on the three-types of Maillard products (KG-19, KG-24 and KG-32) prepared from this Research Institute. Throughout the observation period of the acute toxicity study in rats and the mutagenicity assay using Salmonella typhimurium (TA98, TA100), the test articles did not show any sigificant toxic or mutagenic signs.
PROTECTIVE EFFECT OF SCOPARONE AGAINST ACETAMINOPHEN INDUCED LIVER TOXICITY IN MICE
Huh, Keun ; Park, Jong-Min ; Chung, Jung-Rok ;
Toxicological Research, volume 3, issue 2, 1987, Pages 121~128
Protective effect of scoparone against the acetaminophen inducible hepatic toxicity in mice was investigated. Scoparone (5mg/kg) was administered intraperitoneally to mice daily for 5 days. Scoparone pretreatment before the administration of acetaminophen has blocked subsequent increases in liver to body weight ratio. When biological changes were measured, scoparone protects against acetaminophen inducible hepatotoxicity in mice as evidenced by the decreased formation of lipid peroxide, lowered serum transaminase activity and the decreased level of serum acetaminophen. In conjuction with the results of Huh (Arch. Pharm. Res. 10, 165(1987)), these results suggest that the most likely mechanism for the observed protective effects of scoparone against the acetaminophen-induced hepatotoxicity is the induction of hepatic microsomal UDP-glucuronyltransferase activity.
PROTECTIVE ACTION OF N-ACETYLCYSTEINE AGAINST HEPATOTOXIC AGENTS IN ISOLATED RAT LIVER CELLS
Park, Soo-Hee ; Dong, Mi-Sook ; Kang, Dong-Chul ; Lee, Ki-Wan ; Cha, Young-Nam ;
Toxicological Research, volume 3, issue 2, 1987, Pages 129~141
Hepatocytes isolated from rats which have been pretreated with phenobarbital (80 mg/kg for 3 days), were able to take up N-acetylcysteine from surrounding medium and were able to synthesize the reduced glutathione (
) intracellularly. The N-acetylcysteine is quickly deacetylated after the uptake and increases the pool size of cysteine, which was very low initially (5 nmol/
cells). From this increased intracellular cysteine pool, GSH was synthesized. Freshly isolated rat hepatocytes contained a high level of GSH (30 nmol/
cells), but upon incubation with the diethylmaleate, it was markedly decreased (10 nmol/
cells). The hepatocytes with depleted GSH have lost viability upon incubations with acetaminophen (5mM) and paraquat (2 mM). However, when the N-acetylcysteine (1 mM) was added to this incubation condition, these chemical induced hepatocellular necrosis were prevented for longer durations. This N-acetylcysteine dependent protective effect against the hepatotoxic chemicals was lost by adding methionine sulfoximine (10 mM), an inhibitor of GSH biosynthesis. Both the carbontetrachloride (5 mM) and chioroform (5 mM) added to the incubation medium caused rapid losses of GSH and cell viability, even without the prior depletion of cellular GSH. However, again, if the 1mM N-acetylcysteine was supplemented, the rates of losses of GSH and cell viability were retarded in both cases. Even though large amounts of the added N-acetylcysteine was present in the cell, N-acetylcysteine conjugate of acetaminophen was not formed. Instead, only large amounts of GSH conjugate of the drug was produced. Thus, it is concluded that the added N-acetylcysteine is taken up and utilized for resynthesis of GSH. In turn, this resynthesized GSH contributes to the protection against cytotoxicity inducible with hepatotoxic drugs.