Immunotoxicity studies of trans-resveratrol in male BCF/N mice.

Resveratrol is a naturally occurring polyphenol that is being investigated to treat and prevent various diseases, both experimentally and in the clinic. Despite increased use and interest in resveratrol due to its immunomodulatory properties, there is a lack of studies evaluating potential toxicities, particularly immunotoxicity, associated with resveratrol use. A previous 2-week study found decreasing thymus weight in male BCF/N mice with increasing exposure to trans-resveratrol.

Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female BCF mice exposed to hexavalent chromium via the drinking water.

Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function.

Respiratory toxicity and immunotoxicity evaluations of microparticle and nanoparticle C60 fullerene aggregates in mice and rats following nose-only inhalation for 13 weeks.

C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1 nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50 nm [nano-C60] and 1 μm [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks.

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water.

Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent.

Health assessment of gasoline and fuel oxygenate vapors: immunotoxicity evaluation.

Female Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential immunotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) administered for 6h/day, 5days/week for 4weeks.

Genistein protects female nonobese diabetic mice from developing type 1 diabetes when fed a soy- and alfalfa-free diet.

The objective of this study was to determine the effects of the phytoestrogen genistein (GEN) on the time of onset and/or the incidence of type 1 diabetes (T1D) in female nonobese diabetic (NOD) mice, when administered GEN by gavage once every day for up to 180 days. Five groups of mice (approximately 24 animals/group; 6-7 weeks of age) were included: naive control, vehicle control (25 mM Na2CO3 in water), and 3 GEN treatment groups (2 mg/kg, 6 mg/kg, and 20 mg/kg). Mice were maintained on a soy- and alfalfa-free diet (5K96) during the study and were monitored for blood glucose changes every week.

Immunomodulatory activity of orphan drug Elmiron® in female B6C3F1/N mice.

Interstitial cystitis (IC) is a chronic disorder characterized by bladder discomfort and urinary urgency in the absence of identifiable infection. Despite the expanding use in IC treatment and other chronic conditions, the effects of Elmiron® treatment on immune system remain unknown. Therefore, female B6C3F1/N mice were orally administered Elmiron® daily for 28-days at doses of 63, 125, 250, 500 or 1000mg/kg to evaluate its immunomodulatory effects.

Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: a workshop summary.

As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential.

Characterization of the T-dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) in the Göttingen minipig.

Recently, there has been a renewed interest in the use of the minipig as an alternative to dogs and non-human primates for conducting toxicological assessments in non-rodent species. Since the T-dependent antibody response (TDAR) is one of the most widely-accepted assays used in the assessment of immunocompetence, the present study was undertaken to characterize the primary and secondary TDAR to keyhole limpet hemocyanin (KLH) in the Göttingen Minipig(®). Following primary immunization with either 2 or 10 mg KLH, anti-swine IgM and IgG ELISAs were optimized and individual animal responses were evaluated over time.

Route-dependent systemic and local immune effects following exposure to solutions prepared from titanium dioxide nanoparticles.

Nanoparticle titanium dioxide (nano-TiO2) is a white pigment widely used in foods, sunscreens, and other cosmetic products. However, it remains unclear whether exposure to nano-TiO2 results in immunosuppressive effects or induces a contact hypersensitivity response. To address these data gaps, studies were conducted with the hypothesis that nano-TiO2 exposure could alter immune responses.

Jet fuel kerosene is not immunosuppressive in mice or rats following inhalation for 28 days.

Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels.

Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice.

Black cohosh extracts (BCE; Actaea racemosa) are being used worldwide as an alternative to hormone replacement therapy for the management of menstrual and menopausal symptoms, yet the effects of BCE on the immune system are largely unknown. Female B6C3F1/N mice were treated daily with BCE (0, 62.5, 125, 250, 500, or 1000mg/kg) for 28 days by oral gavage.

Autophagy, cell death and sustained senescence arrest in B16/F10 melanoma cells and HCT-116 colon carcinoma cells in response to the novel microtubule poison, JG-03-14.

Purpose: Previous studies have shown that the novel microtubule poison, JG-03-14, which binds to the colchicine binding site of tubulin, has the capacity to kill breast tumor cells primarily through the promotion of autophagy. The current work was designed to determine whether autophagy was, in fact, the primary mode of action as well as susceptibility to JG-03-14 in two additional tumor cell models, the B16/F10 murine melanoma cell line and the HCT-116 human colon cancer cell line.

Methods: Drug cytotoxicity was monitored based on viable cell number and clonogenic survival.

Novel insights on the effect of nicotine in a murine colitis model.

Studies showed that nicotine has a positive influence on symptoms of ulcerative colitis. In the present study, we explored the effect of nicotine treatment using different routes of administration in the dextran sodium sulfate (DSS) colitis mouse model. We also investigated the effects of cotinine, a major metabolite of nicotine, in the model.

Evaluation of innate, humoral and cell-mediated immunity in mice following in vivo implantation of electrospun polycaprolactone.

Electrospun polycaprolactone (EPCL) is currently being investigated for use in tissue engineering applications such as vascular grafts. However, the effects of electrospun polymers on systemic immune responses following in vivo exposure have not previously been examined. The work presented evaluates whether EPCL in either a microfibrous or nanofibrous form affects innate, humoral and/or cell-mediated immunity using a standard immunotoxicological testing battery.

Validation of the Candida albicans delayed-type hypersensitivity (DTH) model in the female B₆C₃F₁ mouse for use in immunotoxicological investigations.

Although numerous models are used to evaluate the immunotoxic effects of xenobiotics on cell-mediated immunity (CMI), no holistic model for evaluating such effects on the delayed-type hypersensitivity (DTH) response has gained widespread acceptance. Due to a lack of interference from antigen-specific antibody production, the Candida albicans DTH model has recently been demonstrated to be a more appropriate model for assessing effects on CMI than other DTH models that utilize different sensitizing antigens, such as sheep erythrocytes (SRBC) or keyhole limpet hemocyanin (KLH). The present studies were conducted to validate the C.

Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days.

Oral subchronic immunotoxicity study of ethyl tertiary butyl ether in the rat.

The potential for immunotoxicological effects of ethyl tertiary butyl ether (ETBE, CAS RN 637-92-3) was studied in young adult female Crl:CD(SD) rats following subchronic oral exposures. Rats were exposed by gavage once daily for 28 consecutive days to 0, 250, 500, or 1000 mg ETBE/kg body weight (BW)/day; a concurrent positive control group received four intraperitoneal injections of at 50 mg cyclophosphamide monohydrate (CPS)/kg/day on study Days 24-27. Immunotoxicity was evaluated using a splenic antibody-forming cell (AFC) assay to assess T-cell-dependent antibody responses in rats sensitized with sheep red blood cells (SRBC).

Contact sensitizing potential of annatto extract and its two primary color components, cis-bixin and norbixin, in female BALB/c mice.

The present studies were performed to examine the contact allergenic effects of an annatto extract (ANT) in female BALB/c mice. ANT at 5-10% induced a greater than threefold increase in lymph node cell proliferation when compared to the control in the LLNA. Moreover, a significant increase in the percent ear swelling at 24h after ANT challenge was observed in the MEST.

Immunotoxicity of dibromoacetic acid administered via drinking water to female B₆C₃F₁ mice.

Dibromoacetic acid (DBA) is a disinfection by-product commonly found in drinking water as a result of chlorination/ ozonation processes. The Environmental Protection Agency estimates that more than 200 million people consume disinfected water in the United States. This study was conducted to evaluate the potential immunotoxicological effects of DBA exposure when administered for 28 days via drinking water to B₆C₃F₁ mice, at concentrations of 125, 500, and 1000 mg/L.

Establishment and comparison of delayed-type hypersensitivity models in the B₆C₃F₁ mouse.

The objective of these studies was to establish and compare delayed-type hypersensitivity (DTH) models, using keyhole limpet hemocyanin (KLH), sheep red blood cells (SRBC), and Candida albicans as sensitizing antigens, for their capability to assess a DTH response (utilizing footpad swelling as the endpoint) with minimal confounding factors resulting from antigen-specific antibody (Ab) production. The key elements of the DTH are the sensitization dose, time interval between sensitization and challenge [i.e.

Immunomodulation in female B₆C₃F₁ mice following treatment with the HIV protease inhibitor saquinavir for 28 days by gavage.

Saquinavir (SQV) is a protease inhibitor that binds to the protease active site of the human immunodeficiency virus and prevents the cleavage of viral polyproteins resulting in the formation of non-infectious virus particles. The purpose of these studies was to determine the potential effects of SQV on the immune system in female B₆C₃F₁ mice. SQV was administered by gavage twice daily for 28 days at total doses of 300, 600, and 1200 mg/kg/day.

Systemic immunosuppression following a single pharyngeal aspiration of 1,2:5,6-dibenzanthracene in female B6C3F1 mice.

1,2:5,6-Dibenzanthracene (DBA) is ubiquitous in our environment as a contaminant produced by incomplete combustion of organics from sources such as forest fires, cigarette smoke, and asphalt paving, and it is more immunosuppressive of the T-dependent antibody-forming cell (AFC) response than the well-studied polycyclic aromatic hydrocarbon, benzo(a)pyrene. The systemic immunosuppressive effects of DBA were investigated following a single pharyngeal aspiration (pa) in female B(6)C(3)F(1) mice. The immunotoxic effects of DBA were evaluated using numerous assays of varying complexity to evaluate innate (natural killer [NK] cell activity), cell-mediated (T-lymphocyte proliferation, mixed leukocyte response [MLR], cytotoxic T-lymphocyte [CTL] activity, delayed-type hypersensitivity [DTH]), and humoral immunity (B-lymphocyte proliferation, T-dependent antibody responses).

Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells.

Studies were performed to determine the influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to adriamycin (doxorubicin) in four human breast tumor cell lines and one murine breast tumor line. Sildenafil did not interfere with the effectiveness of adriamycin in any of the cell lines tested. Sildenafil also failed to protect MDA-MB231 cells against the cytotoxicity of cisplatin, taxol or camptothecin.

The sheep erythrocyte T-dependent antibody response (TDAR).

The sheep erythrocyte T-dependent antibody Response (TDAR) evaluates the ability of animals sensitized in vivo to produce primary IgM antibodies to sheep erythrocytes (sRBC). The assay enumerates the number of antigen specific IgM antibody producing cells in the spleen. When exposure to the test material takes place in vivo, as does sensitization, the actual quantification of the number of antibody producing cells occurs ex vivo.