Joung-Hoon Kim

Effects of the ethanol extract of Cichorium intybus on the immunotoxicity by ethanol in mice

Effects of the ethanol extract of Cichorium intybus (CIEE) on the immunotoxicity of ethanol (EtOH) were investigated in ICR mice. Mice were divided into four groups, and CIEE at dose of 300 mg/kg was orally administered to mice daily for 28 consecutive days, and normal mice were given vehicle. Mice treated with EtOH were given freely with 20% w/v EtOH solution. The results of this study are summarized as follows: The combination of CIEE and EtOH showed significant increases in the circulating leukocytes and the relative weights of liver, spleen and thymus, as compared with those in mice treated with EtOH alone. However, the body weight gain was not affected. Splenic plaque forming cells (PFC) and hemagglutination (HA) titers to sheep red blood cells (SRBC), and the secondary IgG antibody response to bovine serum albumin (BSA) were markedly enhanced by CIEE plus EtOH treatment as compared with the treatment of EtOH alone. In mice receiving the combination of CIEE and EtOH when compared with EtOH alone-treated mice, there were also significant increases in delayed-type hypersensitivity (DTH) reaction, phagocytic activity, natural killer (NK) cell activity and cell proliferation as well as interferony (IFN-gamma) secretion. In the case of interleukin-4 (IL-4) content, however, an insignificant induction observed by CIEE plus EtOH treatment. These findings indicate that the immunotoxicity induced by EtOH is significantly restored or prevented by CIEE treatment.

Effects of the aqueous extract of Epimedii Herba on the antibody responses in mice

Antibodies and cytokines in serum were detected in male ICR mice treated with the aqueous extract of Epimedii Herba (AEEH) at doses of 40, 120 and 360 mg/kg orally for 2 weeks. Effects of AEEH on antibody forming responses were assessed by enzyme linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected 7 days after priming with ovalbumin (OVA) in complete Freunds adjuvant (CFA) or immediately without priming at week 2. The relative spleen weight was significantly increased by AEEH, compared with controls, especially at a dose of 120 mg/kg of it after priming with OVA and 40 mg/kg without priming, respectively. However, body weight gain was slightly decreased in AEEH-fed mice. The enhancement of total serum IgG and IgG1 levels in unprimed mice was statistically significant in mice fed 40 mg/kg AEEH. Total serum IgG2a levels and Il-4 secretion were also statistically augmented by all groups of AEEH treatment. A tendency to marked increase of total serum IgM level and IFN-gamma secretion was also observed in mice fed 40 and 120 mg/kg AEEH but not those fed 360 mg/kg AEEH. When mice were immunized with OVA, furthermore, a marked stimulation of antibody formation and cytokines secretion was observed in all groups of AEEH-fed mice compared with controls. These findings indicate that AEEH at therapeutic concentrations enhances the production of antibodies and cytokines in mice, and the enhancing effects are more marked when the mice were immunized with OVA. Thus, these results suggest that AEEH is effective on Th cell functions, and protective effects on host against immune diseases.

Influence of melatonin on immunotoxicity of lead

The results suggested that immunotoxicity induced by lead [Pb, as Pb(NO(3))(2)] was significantly restored or prevented by melatonin (MLT). MLT (10 or 50 mg/kg) was orally administered to ICR mice daily for 28 days, and Pb was also administered at 35 mg/kg in the same way 2 h after the administration of MLT, and the normal mice were given vehicle. Within the Pb plus MLT-treated group, the body weight gains and the relative thymus weights were significantly increased when compared with the treatment of Pb alone. The relative spleen and liver weights were increased by the treatment of Pb alone, and then restored to normal value by MLT treatment. Hemagglutination (HA) titer, plaque-forming cell response to sheep red blood cell (SRBC), and secondary IgG antibody response to BSA were significantly enhanced in the Pb plus MLT-treated mice, as opposed to when compared with the treatment of Pb alone. The mitogenic response of splenic T cell to concanavalin A and that of B cells to lipopolysaccharide was remarkably increased by MLT treatment when compared with treatment of Pb alone. Splenic CD4(+)cells were significantly increased by MLT treatment when compared with treatment of Pb alone. In case of CD8(+) cells, the slight enhancement was observed in MLT treatment. Splenic T and B cells were significantly increased by MLT treatment when compared with the treatment of Pb alone. The natural killer cell, phagocytic activity and the number of peripheral leukocytes were significantly enhanced in Pb plus MLT-treated mice when compared with the treatment of Pb alone.

Influence of melatonin on immunotoxicity of cadmium.

The results suggested that immunotoxicity induced by Cd was significantly restored or prevented by MLT. MLT (10 or 50 mg/kg) was orally administered to ICR mice daily for 28 consecutive days, and cadmium (Cd, as [Cd(AC)(2)]) was also administered at 25 mg/kg by the same route 2 h after the administration of MLT, and the normal mice were given vehicle. Within the Cd plus MLT-treated group, the body weight gains and relative thymus weights were significantly increased when compared with the treatment of Cd alone. The relative spleen and liver weights were increased by treatment of Cd alone, then restored to normal value by MLT treatment. Hemagglutination (HA) titer, primary IgM antibody response to SRBC, and secondary IgG antibody response to BSA was significantly increased with the Cd plus MLT-treated mice, as opposed to when compared with treatment of Cd alone. The NK cell and phagocytic activity used for evaluation of non-specific immunocompetence was significantly increased in Cd plus MLT-treated mice when compared with the treatment of Cd alone. The number of peripheral leukocytes was significantly increased in Cd plus MLT-treated mice when compared with treatment of Cd alone.

Induction of oral tolerance to Japanese cedar pollen

Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total IgE level and anti-JCP lgG1 level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP, and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

Effect of biphenyl dimethyl dicarboxylate on the humoral immunosuppression by ethanol

The present study was undertaken to investigate the effect of biphenyl dimethyl dicarboxylate (PMC) on the humoral immunosuppression by ethanol (EtOH) in ICR mice. PMC at a dose of 6 mg/kg was orally administered to mice daily for 28 consecutive days, and the control mice were given vehicle. Mice treated with EtOH were given freely with 20% EtOH instead of water. The results of this study are summarized as follows; a gain of body weight and the relative weights of spleen and liver were significantly increased by combination of PMC and EtOH, as compared with those in mice treated with EtOH alone. Splenic plaque forming cells (PFC) and hemagglutination (HA) titers to sheep red blood cells (SRBC), and the secondary IgG antibody response to bovine serum albumin (BSA) were decreased by the treatment of EtOH alone, then restored to normal level by PMC treatment. The elevations of serum glutamic-pyruvic transaminase (S-GPT) and total protein levels caused by EtOH were reduced to normal level by the combination of PMC and EtOH. In addition, lower serum albumin and A/G ratio were also increased to normal level. These findings indicate that PMC has a protective effect against EtOH-induced humoral immunosuppression.

Potentiation of the immunotoxicity of ethanol by acetaminophen in mice

To investigate the influences of acetaminophen (APP) on the immunotoxicity of ethanol (EtOH) in ICR mice, APP at a dose of 100 mg/kg was orally administered to mice daily for 28 consecutive days. Mice treated with EtOH were given freely with 20% w/v EtOH during the experimental period, and normal mice were given vehicle. The results of this study are summarized as follows: the combination of APP and EtOH significantly decreased the circulating leukocytes and the relative weights of liver, spleen and thymus, compared with the treatment of EtOH alone. In mice receiving the combination of AAP and EtOH when compared with the treatment of EtOH alone, there were also significant reductions in the splenic plaque forming cells (PFC) and hemagglutination (HA) titers to sheep red blood cells (SRBC), and the secondary IgG antibody response to bovine serum albumin (BSA). A tendency toward suppression of delayed-type hypersensitivity (DTH) reaction and phagocytic activity was also observed in the combination of AAP and EtOH. In addition, the combination of AAP and EtOH greatly increased serum alanine aminotransaminase (ALT) and total protein levels, compared with the treatment of EtOH alone. Significant decreases in serum albumin and A/G ratio were observed in EtOH alone-fed mice compared with those in normal animals, and their reductions were further induced in mice treated with AAP and EtOH. These findings indicate that EtOH-induced immunotoxicity is aggravated by the combination of APP and EtOH.

In vitro metabolism of the new insecticide flupyrazofos by rat liver microsomes

1. The in vitro metabolism of the new insecticide flupyrazofos was studied using rat liver microsomes. Two metabolites were produced and identified as O,O-diethyl O-(1-phenyl-3-trifluoromethyl-5-pyrazoyl) phosphoric acid ester (flupyrazofos oxon) and 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole (PTMHP) based on UV and mass spectral analysis. 2. Cytochrome P450 oxidatively converted flupyrazofos to flupyrazofos oxon, a major metabolite and phenobarbital-induced microsomes increased this desulphuration by 8-fold. 3. Flupyrazofos oxon was converted to PTMHP with a half-life of 47.8 min by chemical hydrolysis and this conversion also proceeded non-enzymatically under our microsomal incubation conditions.

The effects of plantago-mucilage A from the seeds ofPlantago asiatica on the immune responses in ICR mice

Effects of plantago-mucilage A (P-MA) on the immune responses were studied in ICR mice. Mice were divided into 4 groups (10 mice/group), and P-MA at doses of 7, 21 and 63 mg/kg were orally administered to mice once a day for 21 consecutive days. Mice were immunized and challenged with sheep red blood cells (SRBC). P-MA at 63 mg/kg/day significantly increased the body weight gain and the relative weights of spleen and thymus, as compared with those in controls. However, there were no significant effects on liver weight due to P-MA treatment. Plaque forming cells (PFC) and hemagglutination (HA) titers to SRBC were significantly enhanced in mice dosed at 21 and 63 mg/kg/day P-MA, as compared with those in controls. Delayed-type hypersensitivity (DTH) reaction to SRBC, phagocyte activity and circulating leukocyte were also significantly increased in mice dosed at 63 mg/kg/day P-MA. These results demonstrate that P-MA markedly enhances both humoral immune and allergic reaction to SRBC at concentrations which don’t act on the relative weight of liver.