• Toxicological Research
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• v.16 no.4
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• pp.317-323
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• 2000

The immunosuppressive effects of thirty nine chemicals chosen by their potential toxicity were evaluated using a three-step testing method. The immunotoxicity test method developed in this study consisted of three simple assays of lymphoproliferation, mixed leukocyte response, and interleukin (IL)-2 production. The first step was mitogen-induced proliferation assay. Ten chemicals showed the inhibitory effects on the mitogen (lipopolysaccharide or concanavalin A)-induced proliferation in dose-dependent manners. The second step was mixed lymphocyte response. This step crosschecked the growth-suppressive effects detected at the first step. All of 10 chemicals, which showed suppression of lymphoproliferation, also exhibited the suppressive effects on the mixed lymphocyte response in the similar range of chemical concentration. The third step was planned to determine whether or not this growth suppression was mediated through an early activation of T-cell, which could be represented with IL-2 production. Six out of 10 chemicals decreased the interleukin-2 production in the similar concentration range used in the step 1 and 2. These results suggest that those 6 chemicals might have their targets on the signal transduction path-way toward the IL-2 production. In the meantime the other 4 chemicals might have their targets after the IL-2 production signal. Taken all together, the three-step test would be simple, fast, and efficient to deter-mine whether or not the chemical has immunosuppressive effects.

• Toxicological Research
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• v.15 no.1
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• pp.39-45
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• 1999

To investigate the preventive effects of melatonin (MLT) on the immunotoxicity of cadmium acetate[Cd(AC)2] in ICR mice, Mlt(10,50mg/kg as cadmium) were orally administered to mice once a day (5:00, PM) for 28 consecutive days. Cadmium(Cd) test solution was also administered at 25mg/kg of cadmium through the same route 2hr after administration of MLT daily, Mice were immunized and challenged with sheep red blood cells (SRBC). Immune functions evaluated were delayed type hypersensitivity (DTH) response, mitogenic response, and flow cytometry analysis. The results of these studies were summarized as follows ; DTH response was abnormally increased in mice treated with Cd alone. DTH response was normally depressed in mice treated with Cd plus MLT along with the increase of MLT doses. The mitogenic response of splenic T cell to Con A and that of B cells to LPS was remarkably increased by MLT treatment as compared with treatment of Cd alone In case of CD 8+ cells, the slight increase was observed in MLT treatment. Splenic T cells and B cells were significantly increased by MLT treatment as compared with treatment with Cd alone. These results suggest that MLT has significant preventive effects on the immunotoxic status induced by Cd exposure.

• Toxicological Research
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• v.26 no.2
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• pp.101-108
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• 2010

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.781-789
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• 2004

The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzy-loxyresorufin- and pentoxyresorufin-D-dealkylases and erythromycin N-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioace-tamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepato-toxicity and immunotoxicity.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.42-58
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• 2002

Acute Cd exposure produces hepatotoxicity, whereas chronic Cd exposure produces nephrotoxicity, hematotoxicity, immunotoxicity and bone damage. Previous experiments suggest that the low-molecular-weight, metal-binding protein metallothionein (MT) in liver protects against liver injury, but is responsible for the kidney injury observed after chronic Cd exposure.(omitted)

• Journal of Food Hygiene and Safety
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• v.5 no.3
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• pp.111-120
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• 1990

Effects of royal jelly(RJ) on the immune system in normal and cyclophosphamide(CY)-treated mice were investigated. The results were as following: 1. Body weight, spleen weight, thymus weight, WBC, cell-mediated immunity (CMI, contact hypersensitivity to DNFB), humoral immunity (HI, Hemagglutinin-, Hemolysin-titer) were increased or decreased dependent on the day of administration of RJ in normal mice. But it showed no effect on liver weight and RBC. 2. Combined treatment with RJ in CY-treated mice on the day which RJ showed the increasing activities in normal mice inhibited the decrease of survival rate, body weight, spleen weight, WBC and CMI caused by CY, but no effect on the decrease of thymus weight and HI induced by CY.

• Toxicological Research
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• v.17
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• pp.25-35
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• 2001

In 1990, Tolerable Daily Intake (TDI) of 10 pg TCDD/kg/day for dioxins based on carcinogenicity and reproductive toxicity was determined by WHO/EURO, that resulted in the establishment of TDIs in other countries. In Japan, Ministry of Health and Welfare and Environment Agency, respectively established the TDI of 10 pg TCDD/kg/day and Health Risk Assessment Index of 5 pg TCDD/kg/day in 1996. Accumulation of new scientific data, especially by molecular toxicology since 1990, resulted in the reevaluation of TDI by WHO-ECEH and IPCS in May, 1998. At this meeting, it was stressed that \circled1 toxic effects of dioxin is mediated through Ah-receptor in both animals and humans, \circled2 use of ebody burdeni concept is better than the use of traditional NOAEL/UF approach, \circled3 inclusion of coplanar PCBs in the TDI by the use of new WHO-TEF. LOAELs (0.16~200 ng TCDD/kg/day) obtained from reproductive toxicity and immunotoxicity in rats, and neurobehavioral toxicity and induction of endometriosis in rhesus monkeys are calculated to be the body burden of 10~50 ng TCDD/kg that is 14~37 pg TEQ/kg/day as human daily intake. Finally TDI of 1~4 pg TEQ/kg/day was established by applying the UF of 10. In Japan, reproductive toxicity and immunotoxicity in rats were used to obtain LOAELs (100~200 ng TCDD/kg/day). Finally TDI of 4 pg TEQ/kg/day was established in June 1999 by applying the UF of 10 to human daily intake of 43.6 pg TEQ/kg/day which corresponds to the body burden of 86 ng TCDD/kg.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.207-215
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• 2009

Despite wide therapeutic use of CpG ODN against infection, allergy and cancer, the safety and toxicity of CpG ODNs were poorly delineated. Thus, we investigated whether optimal dosing of CpG ODN would affect immunotoxicological parameters in NZB/NZW F1 mice. Comparisons were made among control, non-CpG ODN and mouse CpG ODN ($10{\mu}g$)-treated groups for 4 weeks. To gauge the immunotoxicity of CpG ODNs, we measured nonspecific parameters, degree of lupus nephritis, proteinuria, or autoantibody, and cytokine expression in mRNA level of lymphocytes. We found that there were no significant differences among groups in nonspecific immunotoxicological profiles and in evaluation profiles of glomerulonephritis. However, titer of anti-dsDNA and anti-cardiolipin antibodies in mouse CpG ODN group rose three or eight-fold higher than in control group. Collectively, CpG ODN might be clinically less immunotoxic in terms of clinical profiles in lupus-prone NZB/NZW F1 mice, in spite of high autoantibody titer in CpG ODN treated groups.

• Journal of Yeungnam Medical Science
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• v.35 no.2
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• pp.156-164
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• 2018

Environmental contaminants are one of the important causal factors for development of various human diseases. In particular, the perinatal period is highly vulnerable to environmental toxicants and resultant dysregulation of fetal development can cause detrimental health outcomes potentially affecting life-long health. Perfluoroalkyl compounds (PFCs), emerging environmental pollutants, are man-made organic molecules, which are widely used in diverse industries and consumer products. PFCs are non-degradable and bioaccumulate in the environment. Importantly, PFCs can be found in cord blood and breast milk as well as in the general population. Due to their physicochemical properties and potential toxicity, many studies have evaluated the health effects of PFCs. This review summarizes the epidemiological and experimental studies addressing the association of PFCs with neurotoxicity and immunotoxicity. While the relationships between PFC levels and changes in neural and immune health are not yet conclusive, accumulative studies provide evidence for positive associations between PFC levels and the incidence of attention deficit hyperactivity disorder and reduced immune response to vaccination both in children and adults. In conclusion, PFCs have the potential to affect human health linked with neurological disorders and immunosuppressive responses. However, our understanding of the molecular mechanism of the effects of PFCs on human health is still in its infancy. Therefore, along with efforts to develop methods to reduce exposure to PFCs, studies on the mode of action of these chemicals are required in the near future.

• Toxicological Research
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• v.20 no.4
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• pp.365-374
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• 2004

Inhalation toxicity, mutagenicity, and immunotoxicity tests were performed using a smoke generation system to investigate the safety of Herbrette, a tobacco substitute made with the leaves of Perilla frutescens. ICR mice were exposed to nicotine-free Herbrette smoke with concentrations of 0 (control), 4.08 $\pm$ 1.32 mg/$m^3$ (low dose), 7.72 $\pm$ 2.14 mg/$m^3$ (medium dose) and 12.83 $\pm$ 1.69 mg/$m^3$ (high dose) total particulate matters (TPM) for 4 weeks. When compared to the control group, the body weights, organ weights in the exposed groups did not show any significant differences. However, certain change of several serum chemical data and biochemical parameters were observed, however, the changes were within normal physiological ranges. Moreover, no changes in organ weight, and no gross/microscopic changes were observed between the exposed and control groups. Salmonella typhimurium reverse mutation, in vivo chromosomal aberration and micronucleus assays revealed that Herbrette did not induce mutagenicity. Upon evaluation of peripheral cellular immunity of mice through in vitro lymphocyte proliferation assay, no significant difference was observed in mean stimulation index between the exposed and control groups. Taken together, our results strongly suggest that Herbrette may not cause toxicity on mice under current condition.