Jae-Baek Kim

Protective effect of curcumin in rat liver injury induced by carbon tetrachloride

This study was carried out to investigate the protective effects of curcumin on acute or subacute carbon tetrachloride‐induced liver damage in rats.

Effect of Rehmannia glutinosa on immediate type allergic reaction

We investigated the effect of aqueous extract of Rehmannia glutinosa steamed root (RGAE) on the allergic reactions in vivo and in vitro. RGAE dose-dependently inhibited systemic allergic reaction induced by compound 48/80. When RGAE was pre-treated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. RGAE dose-dependently inhibited skin allergic reaction activated by anti-dinitrophenyl (DNP) IgE. RGAE also dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 or anti-DNP IgE. Moreover, RGAE had significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production of RPMC. These results indicate that RGAE may be beneficial in the regulation of immediate type allergic reaction.

Differential expression of protein kinase C genes in cultured mast cells derived from normal and mast-cell-deficient mice and mast cell lines.

We investigated the expression of mRNA of protein kinase C (PKC) isozymes (alpha, beta, gamma, delta, epsilon, xi, and eta) in cultured mast cells (CMC) derived from normal (+/+) mice, CMC derived from genetically mast-cell-deficient (W/W, Wv/Wv, and mi/mi) mice, and murine mast cell lines (IC2, MC9, and P-815) by Northern blotting. In +/+ CMC, abundant expression of PKC delta and moderate expression of PKC alpha and beta was observed, while other PKCs (types gamma, epsilon, xi, and eta) were not detected. In vivo expression of PKC delta was demonstrated in the skin by in situ hybridization. In mast cell lines, the expression pattern of PKC isozymes was similar to that of +/+ CMC, except that the expression of PKC eta was detected in the IC2 cell line. The expression levels of PKC delta in CMC derived from c-kit-deficient mutants, W/W, Wv/Wv, and mi/mi, were lower than that of +/+ mice. These results indicate that PKC delta is the main isozyme in various types of murine mast cells and also suggest that the reduced level of PKC delta expression in mutant mice may be caused by a deficit in the signal transduction system through c-kit receptor.

Biotransformation of theophylline in cirrhotic rats induced by biliary obstruction.

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by biliary obstruction when aminophylline (8 mg/kg as theophylline, i.v.) was administered. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes and the changes in the activity of drug metabolizing enzymes, which are suggested to be involved in theophylline metabolism, were determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to 30% of the control value while AUC (area under the plasma concentration-time curve) and (t1/2)β were increased 1.3 fold and 3.5 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to 30% of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N-demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related), which were reported to be related with theophylline metabolism, were decreased to 67%, 53% and 76% that of normal rat liver, respectively. From the results, it can be concluded that in cirrhotic rats induced by biliary obstruction, the total body clearance of theophylline is markedly reduced and it may be due to decreased activity of drug metabolizing enzymes in liver.

HPLC Assay and Bioequivalence Evaluation of Biphenyl Dimethyl Dicarboxylate (DDB) Products

Abstract A high-performance liquid chromatographic (HPLC) method was developed for biphenyl dimethyl dicarboxylate (DDB) detection in human serum and bioequivalence (BE) of two commercial DDB tablets was evaluated in 14 normal male subjects. The most suitable extracting solvent for DDB in serum was evaluated among dichloromethane, ether, ethylacetate, hexane, and pentane. Pentane:ether (9:1) mixture showed good extraction recovery of DDB from serum and also excluded serum components, which interfere the peak of DDB when assayed. HPLC conditions were as follows: UV absorbance detector, 280 nm; column, μ-Bondapak C

A study for regulation of ethanol-inducible P450(CYP2E1) on CCl4-induced hepatic damage

Previous study showed that CCl4 administration evoked a rapid decrease in cytochrome P450 2E1 protein soon after the exposure due to posttranslational inhibition(Biochem. Biophys. Res. Commun. 179:449–454, 1991). In this report, aniline hydroxylase and the amounts of immunoreactive P450 2E1 were rapidly decreased during day 1 to 2 and recovered during day 3 to 4 after a single dose of CCl4. The activity of pentoxyresorufin-0-dealkylase was also suppressed at day 1 and began to repair from day 2. However, the decrease in immunoreactive P450 2C content was not observed. The decreases in P450 2E1 enzyme activity and immunoreactive protein by acute CCl4 treatment were accompanied by a decline in P450 2E1 mRNA level. The data thus suggested a pretranslational reduction of P450 2E1 during day 1 to 2 after acute CCl4 treatment.

Effect of ion pairing on the cellular transport of antisense oligonucleotide.

Antisense oligonucleotide represents an interesting tool for selective inhibition of gene expression. However, their low efficiency of introduction within intact cells remains to be overcome. Antisense-TGFβ (25 mer) and antisense-TNFα (18 mer) were used to study the cellular transport and biological function of antisense oligonucleotide in vitro. Since TGF and TNF play on important role in regulating the nitric oxide production from macrophages, the action of the above antisense oligonucleotides was easily monitored by the determination of nitrite. Poly-L-lysine, benzalkonium chloride and tetraphenylphosphonium chloride were used as polycations, which neutralize the negative charge of antisense oligonucleotide. The production of nitric oxide mediated by γ-IFN in mouse peritoneal macrophage was increased by antisense-TGFβ in a dose-dependent manner. Antisense-TNFα reduced the nitric oxide release from activated RAW 264.7 cells. Significant enhancement in the nitric oxide production was investigated by the cotreatment of poly-L-lysine with antisense-TGFβ. On the meanwhile, inhibition effect of antisense-TNFα is not changed by the addition of poly-L-lysine. These results demonstrate that control of expression of TGFβ and TNFα gene is achieved using antisense technology and the cellular uptake of antisense oligonucleotide could be enhanced by ion-pairing.