Immune System Of Rats Research Articles

Immune proteasomes in the development of the rat immune system

The dynamics of the expression of LMP7 and LMP2 proteasome subunits in embryonic and early postnatal development of rat spleen and liver is investigated in comparison with the dynamics of chymotrypsin-like and caspase-like proteasome activities and expression of MHC (major histocompatibility complex) class I molecules. The immune subunits LMP7 and LMP2 distribution in spleen and liver cells in the development process is also studied. A mutual for both organs tendency to the increase of the expression of both LMP7 subunit and LMP2 one on P21 (the 21st postnatal day) as compared to the embryonic period is discovered. However, the total proteasome level is shown to be constant. At definite development stages, the dynamics of immune subunits expression in the spleen and liver was different. In the spleen gradual enhancement of both immune subunits level being detected on P1, P18 and P21, in the liver gradual enhancement periods on E16 (the 16th embryonic day) and E18 changed to the stage of the shrink of immune subunits level on P5. This level did not reliably change till P18 and was augmented on P21. The alterations revealed were accompanied by chymotrypsin-like activity raise and caspase-like activity drop in spleen by P21 as compared with the embryonic period, which proves the enlargement of proteasome ability to form antigenic epitopes for MHC class I molecules. In the liver, both activities increased by P21 in comparison with the embryonic period. Such dynamics of caspase-like activity can be explained not only by the change of proteolytic constitutive and immune subunits, but also by additional regulatory mechanisms. Besides, it is discovered that the increment of immune subunits expression in the early spleen development is connected with the process of successive forming the white pulp by B- and T-lymphocytes enriched by immune subunits. In the liver, the growth of immune subunits level by P21 was accompanied by their expression expansion in hepatocytes, while their plunge by P5 may be related to the loss of liver function of a primary lymphoid organ of the immune system by this stage and disappearance of B-lymphocytes enriched by immune proteasomes in it. In the spleen and liver, MHC class I molecules were revealed at the periods of the raise of proteasome immune subunits level. On E21 , the liver was enriched by neuronal NO-synthase, its level decreased after birth and enhanced to P18. This fact indicates the possibility of the induction of the immune subunits LMP7 [character: see text] LMP2 expression in hepatocytes in signal way with neuronal NO-synthase participation. The results obtained prove that T-cell immune response with spleen participation as regards rat liver cells is possible starting with P19-P21 stage. First, at this period, white pulp T-area is formed in the spleen. Second, enhanced immune proteasomes and MHC class I molecules levels in hepatocytes can procure antigenic epitopes formation from foreign proteins and their delivery to cell surface for their subsequent presentation for cytotoxic T-lymphocytes.

Effects of maternal silver acetate exposure on immune biomarkers in a rodent model (P1030)

Abstract The bacteriocidal effects of silver mixtures are well characterized and as a consequence they are used worldwide in many food contact substances. However, the long-term effect of silver ion exposure on the developing immune system has not been well studied. In this study, 50 d old male and female rats were exposed to 0.4, 4 or 40 mg/Kg body weight silver acetate (AgAc) in drinking water for 10 wk prior to mating and during the 3 week mating period. Sperm positive females remained within their dose groups and were exposed to AgAc during gestation and lactation. Splenic and thymic lymphocyte subsets from postnatal (PN) 4 and 25 d old pups were assessed by flow cytometry for changes in immune biomarker profile. Functional indices included natural killer (NK) activity and mitogen-induced lymphocyte proliferation. Spleens from PN 4 d pups had lower percentages of CD8+ lymphocytes in 4 and 40 AgAc groups; lower CD3 in 40 AgAc group, and reduced Con A response in all 3 AgAc groups. In PN 25 d pups, splenocytes from 40 mg AgAc fed rats had a higher B cell population. However, Con A and LPS mediated lymphocytic responses were significantly reduced in this group. Further, splenic NK activity was higher in PN 25 d old pups exposed to 0.4 AgAc diet. In conclusion, maternal exposure to AgAc had a significant impact on rat immune system development especially in the early lactation period.

Dietary modulation of BALT on a rat mammary tumor model

Murine bronchus associated lymphoid tissue (BALT) is a mirror of systemic immunity since it varies greatly with immune status of the animal and plays a pivotal role in local immune responses at the lung surface. BALT enhanced histopathology (EH) is a semiquantitative screening tool to determine whether there is a potential effect on the immune system of rats under controlled conditions.168 Sprague Dawley virgin female rats with 42 days were randomly distributed for seven groups of 24 animals each. Besides group I, at 55 days the groups were induced for mammary cancer with 20mg of 1,12‐dimetilbenzantracene (DMBA). Dietary protocols were applied for 150 days as following. Group I: standard diet (SD), 300Kcal/100g; Group II: DMBA +SD; Group III: SD + beans 40g/Kg of SD, 341Kcal/100g; Group IV: SD + olive oil (50ml/Kg of SD); Group V: fiber supplement 4× the SD, 250Kcal/100g; Group VI: fiber supplement 4× the SD + beans 19,95gr + olive oil 25ml on 1Kg of SD; Group VII: SD + mediterranean lyophilized diet (41Kcal). The animals were ethically euthanized and the lungs were routinely fixed and stained with hematoxylin‐eosin. BALT was evaluated by EH.The BALT morphology of tumoral rats with mediterranean diet and caloric restrain was similar to the BALT of control group. The other tumoral groups had decreased BALT in size and lymphocyte number compared to control group.These results suggest that diet can interfere on BALT morphology.

Cocoa modulatory effect on rat faecal microbiota and colonic crosstalk

Previous studies have reported the effect of a cocoa-enriched diet on the intestinal immune system in rats. Cocoa contains fibre and polyphenols that can directly influence the intestinal ecosystem and its relationship with the immune system. The aim of this study was to evaluate the effects of a cocoa-enriched diet on gut microbiota, toll-like receptor (TLR) expression and immunoglobulin (Ig) A (IgA) intestinal secretion in rats. Four-week-old Wistar rats were fed a standard or cocoa diet for 6weeks. Faecal samples were collected before the beginning of the diet and at the end of the study. After the nutritional intervention, colon samples were obtained to quantify TLR and IgA gene expression and IgA protein. Microbiota composition was characterized by fluorescent in situ hybridization (FISH) coupled to flow cytometry (FCM) analysis using specific probes directed to 16S rRNA of the main bacteria genus present in rat intestine. The cocoa dietary intervention resulted in a differential TLR pattern and a decrease in the intestinal IgA secretion and IgA-coating bacteria. Moreover there was a significant decrease in the proportion of Bacteroides, Clostridium and Staphylococcus genera in the faeces of cocoa-fed animals. In conclusion, cocoa intake affects the growth of certain species of gut microbiota in rats and is associated with changes in the TLR pattern which could be responsible for the changes observed in the intestinal immune system.

The effect of catecholamine deficit on the development of the immune system in rats

The effect of catecholamine deficit on the development of the immune system in rats

Effect of garlic consumption on the argyrophilic nucleolar organiser regions (AgNORs) in splenocytes and thymocytes of rats

The number and size of nucleolar organiser regions (NORs) are related to cell proliferation. To test the hypothesis that lymphocyte proliferation is associated with garlic consumption, 17 6-week-old male Wistar rats were separated into two groups. For 30 days eight rats were given garlic solution by gavage while the remaining nine animals received distilled water. Silver staining of NORs was performed on the fixed tissues of spleens and thymuses. The nuclear area (NA), nuclear length (NL), total AgNORs area (TAA), total AgNORs length (TAL) and total AgNORs number (TAN) of 100 analyzable nuclei of lymphocytes from each tissue were recorded. In spite of a decline in the average NA and NL of thymocytes from garlic-treated rats (p<0.001), TAA and TAL increased significantly (p<0.001) in the splenocytes and thymocytes of this group. In conclusion, garlic may enhance the lymphocyte proliferation in these two important organs from the rat immune system.

Effect of heat stress and ergopeptine alkaloids on the immune system of rats

Rats were fed diets containing alkaloids (E+), minus alkaloids (E−), or pair‐fed (PF to E+). Groups were further divided into temperature treatments of thermoneutrality (TN; 21°C) or heat stress (HS; 33°C). Rats received diet treatments at TN for 1 week followed by 3 days HS or TN treatment. Feed intake and body weight were reduced by alkaloids, heat stress, and combination of both stressors. Feed intake was reduced 82% from preheat level in E+HS rats compared to 75% in HS rats. Blood samples were collected at trial end and analyzed by flow cytometry. Natural killer (NK) cells increased with all stressors, such that E+HS level was twice that of E‐TN rats (4.2% vs. 2.1%; α=0.05). Caloric restriction (HS and TN) modestly increased NK cells. The combination of stressors dimished B cells by one‐half (α=0.05) compared to E‐TN. Treatment differences in T cell percentage, however, were not statistically significant. In summary, combination of alkaloid intake and heat stress significantly affected the proportion of circulating NK and B cells, with more modest changes in T cells. Caloric restriction (PF) increased NK cells, regardless of environmental conditions. (USDA Agreement No. 58‐6227‐3‐016)

In vivo immunomodulatory activities of the aqueous extract of bonduc nut Caesalpinia bonducella seeds

This study evaluated the in vivo immunomodulatory activities of the aqueous extract of Caesalpinia bonducella Fleming (Caesalpiniaceae) seeds. C. bonducella is a plant widely used in the traditional medicinal systems of India. In the present investigation, the aqueous extract of C. bonducella seeds was tested for its effect on cell mediated and humoral components of the immune system in rats. Administration of C. bonducella seed extract produced an increase of 93.03 ± 4 mean hemagglutinating antibody (HA) titer and a change of 0.56 ± 0.058 mm in delayed type hypersensitivity (DTH) as compared to control at a dose of 400 mg/kg body weight. Thus, the results of this study indicate that C. bonducella extract could be a promising immunostimulatory agent.

Ontogenesis of rat immune system: Proteasome expression in different cell populations of the developing thymus

Immune proteasomes in thymus are involved in processing of self-antigens, which are presented by MHC class I molecules for rejection of autoreactive thymocytes in adults and probably in perinatal rats. The distribution of immune proteasome subunits LMP7 and LMP2 in thymic cells have been investigated during rat perinatal ontogenesis. Double immunofluorescent labeling revealed LMP7 and LMP2 in thymic epithelial and dendritic cells, as well as in CD68 positive cells – macrophages, monocytes – at all developmental stages. LMP2 and LMP7 were also detected by flow cytometry in almost all thymic CD90 lymphocytes through pre- and postnatal ontogenesis. Our results demonstrate that the immune proteasomes are expressed in all types of thymic antigen presenting cells during perinatal ontogenesis, suggesting the establishment of the negative selection in the thymus at the end of fetal life. The observation of the immune proteasome expression in T lymphocytes suggests their role in thymocyte differentiation besides antigen processing in thymus.

Influence of breast milk polyamines on suckling rat immune system maturation

The aim of this study was to ascertain whether the supplementation of polyamines present in breast milk, i.e. spermine (SPM) and spermidine (SPD), influenced the post-natal maturation of the systemic and intestinal immune system in rats. From birth, pups daily received SPM or SPD. At 5, 11 and 18 days old, small intestine intraepithelial lymphocytes (IEL), lamina propria lymphocytes (LPL) and splenocytes were phenotypically characterized. SPM and, less evidently, SPD accelerated the maturation of CD8+ IEL, and enhanced the presence of intraepithelial NK cells and IEL related with specific immune responses on the proximal and distal small intestine, respectively. Polyamines increased the percentage of more mature CD4+ LPL and enhanced the early presence of splenic B cells and, later, that of NK cells. However, no effect on Ig-secretory function was detected. These results suggest that breast milk polyamines improve the maturation of the rat intestinal and systemic immune system.

TheAnisakis simplexAni s 7 major allergen as an indicator of trueAnisakisinfections

Ani s 7 is currently the most important excretory/secretory (ES) Anisakis simplex allergen, as it is the only one recognized by 100% of infected patients. The allergenicity of this molecule is due mainly to the presence of a novel CX(17-25)CX(9-22)CX(8)CX(6) tandem repeat motif not seen in any previously reported protein. In this study we used this allergen as a model to investigate how ES allergens are recognized during Anisakis infections, and the usefulness of a recombinant fragment of Ani s 7 allergen (t-Ani s 7) as a marker of true Anisakis infections. The possible antigenic relationship between native Ani s 7 (nAni s 7) from Anisakis and Pseudoterranova decipens antigens was also investigated. Our results demonstrate that nAni s 7 is secreted and recognized by the immune system of rats only when the larvae are alive (i.e. during the acute phase of infection), and that this molecule is not present in, or is antigenically different from, Pseudoterranova allergens. The t-Ani s 7 polypeptide is a useful target for differentiating immunoglobulin E antibodies induced by true Anisakis infections from those induced by other antigens that may cross-react with Anisakis allergens, including P. decipiens. The results also support the hypothesis that the Ani s 7 major allergen does not participate in maintaining the antigenic stimulus during chronic infections.

Immunomodulatory Effects of Dietary Potassium Perfluorooctane Sulfonate (PFOS) Exposure in Adult Sprague-Dawley Rats

Perfluorooctanesulfonate (PFOS) is a stable and environmentally persistent metabolic or degradation product of perfluorooctanyl compounds that were manufactured for a variety of industrial and consumer applications. PFOS itself was sold for use as a surfactant. The structurally related contaminants perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), and N-ethyl perfluorooctane sulfonamide (N-EtPFOSA) were shown to suppress immune responses in laboratory rodents. Relatively low doses of PFOS were found to be immunosuppressive in mice. To assess effects of PFOS on the rat immune system at doses known to alter hepatic function, changes in the morphology and function of immune tissues and cells were measured in adult rats exposed to PFOS in their diet for 28 d at levels ranging from 2 to 100 mg PFOS/kg diet (corresponding to approximately 0.14 to 7.58 mg/kg body weight [bw]/d) and compared to those receiving control diet. Body weight reductions were significant in male and female rats exposed to 50 and 100 mg PFOS/kg diet. Liver/body weight was significantly increased in females exposed to 2 mg PFOS/kg diet and in males exposed to 20 mg PFOS/kg diet. Female rats exposed to 100 mg PFOS/kg diet exhibited a significant increase in spleen weight relative to body weight; these changes lacked a histologic correlate and were not observed in males. While thymus weights relative to body weights were not affected, numbers of apoptotic lymphocytes rose in thymus with increasing dietary PFOS. There was a significant dose-related increase in total peripheral blood lymphocyte numbers in female but not male rats. In both genders the percentages of cells within lymphocyte subclasses were altered. There was a significant trend toward increasing T and T‐helper (Th) cells and decreasing B cells with higher PFOS dose. Serum total immunoglobulin (Ig) G1 levels were significantly reduced in males exposed to 2 and 20 mg PFOS/kg diet. The ability of male and female rats to mount delayed-type hypersensitivity (DTH) responses to the T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was not altered by PFOS. There was a significant trend toward elevated KLH-specific IgG in serum from male rats exposed to increasing levels of PFOS in diet. Splenic T- and B-cell proliferation in response to ex vivo mitogen exposure was unaffected by exposure to dietary PFOS. In conclusion, changes in immune parameters in rat did not manifest as functional alterations in response to immune challenge with KLH and may be secondary to hepatic-mediated effects of PFOS in this model.

Study of watery extract efficacy of Echinacea purpoura on rat immune system

Introduction & aim: Immune system Conflicted by strange ingredient thus microorganisms as bacteria, microbes and extraneous ingredient as toxic compound. Immune stimulation is one of important problems for researchers & pharmacognosic studies shown that Echinacea Purpoura has immune stimulant effect on same laboratory animals. The aim of this study is scrutiny of Echinacea Purpoura watery extract efficacy on rat mice immune system stimulation. Methods: In this study we used of 20 males rat mice (n=10 for each group). First group received physiologic serum and in another group used of watery extract of Echinacea Purpoura in 500 mg/kg dosage during 3 weeks, orally. In next step after blood sampling and purring them serum, laboratory analyses included, Hematocrit, WBC, differential white blood cell count, phagocyte activity (number), total protean, albumin and gamma globulin is done. Results: Result shown that, in watery extract group into the physiologic serum group has significant increasing in differential white blood cell count and gamma globulin level (p

Evaluation of the Immune System in Rats and Mice Administered Linear Ammonium Perfluorooctanoate

Repeated high doses of ammonium perfluorooctanoate (APFO) have been reported to affect immune system function in mice. To examine dose-response characteristics in both rats and mice, male CD rats and CD-1 mice were dosed by oral gavage with 0.3-30 mg/kg/day of linear APFO for 29 days. Anti-sheep red blood cell (SRBC) IgM levels, clinical signs, body weights, selected hematology, and lipid parameters, liver weights, spleen, and thymus weights and cell number, selected histopathology, and serum corticosterone concentrations were evaluated. In rats, linear APFO had no effect on production of anti-SRBC antibodies. Ten and 30 mg/kg/day resulted in systemic toxicity as evidenced by decreases in body weight gain to 74 and 37%, and increases in serum corticosterone levels to 135 and 196% of control, respectively. In mice dosed with 10 and 30 mg/kg/day, marked systemic toxicity and stress were observed, as evidenced by a loss in body weight of 3.8 and 6.6 g, respectively (despite a tripling of liver weight), approximately 230% increase in serum corticosterone, and increases in absolute numbers of peripheral blood neutrophils and monocytes with an accompanying decrease in absolute lymphocyte numbers. Immune-related findings at 10 and 30 mg/kg/day that likely represent secondary responses to the systemic toxicity and stress observed at these doses include: decreased IgM antibody production at 10 (20% suppression) and 30 mg/kg/day (28% suppression); decreased spleen and thymus weights and cell numbers; microscopic depletion/atrophy of lymphoid tissue at 10 (thymus) and 30 mg/kg/day (spleen). In summary, no immune-related changes occurred in rats, even at doses causing systemic toxicity. In mice, immune-related changes occurred only at doses causing significant and profound systemic toxicity and stress.

Immunotoxicity Evaluation of Jet A Jet Fuel in Female Rats After 28-Day Dermal Exposure

The potential for jet fuel to modulate immune functions has been reported in mice following dermal, inhalation, and oral routes of exposure; however, a functional evaluation of the immune system in rats following jet fuel exposure has not been conducted. In this study potential effects of commercial jet fuel (Jet A) on the rat immune system were assessed using a battery of functional assays developed to screen potential immunotoxic compounds. Jet A was applied to the unoccluded skin of 6- to 7-wk-old female Crl:CD (SD)IGS BR rats at doses of 165, 330, or 495 mg/kg/d for 28 d. Mineral oil was used as a vehicle to mitigate irritation resulting from repeated exposure to jet fuel. Cyclophosphamide and anti-asialo GM1 were used as positive controls for immunotoxic effects. In contrast to reported immunotoxic effects of jet fuel in mice, dermal exposure of rats to Jet A did not result in alterations in spleen or thymus weights, splenic lymphocyte subpopulations, immunoglobulin (Ig) M antibody-forming cell response to the T-dependent antigen, sheep red blood cells (sRBC), spleen cell proliferative response to anti-CD3 antibody, or natural killer (NK) cell activity. In each of the immunotoxicological assays conducted, the positive control produced the expected results, demonstrating the assay was capable of detecting an effect if one had occurred. Based on the immunological parameters evaluated under the experimental conditions of the study, Jet A did not adversely affect immune responses of female rats. It remains to be determined whether the observed difference between this study and some other studies reflects a difference in the immunological response of rats and mice or is the result of other factors.

Effects of Exposure to Decabromodiphenyl Ether on the Development of the Immune System in Rats

To evaluate the developmental toxicity of decabromodiphenylether (DBDE) after exposure during the period from late gestation to after lactation, maternal Sprague-Dawley rats were given DBDE at dietary concentrations of 0, 10, 100, and 1000 ppm from gestational day 10 (GD 10) to postnatal day (PND) 21. On PND 21 and 77, lymphocytes (Lymph) in the spleen, thymus, and peripheral blood of male pups were subjected to flow cytometric analyses for expression of surface markers [CD3, CD4, CD8a, CD25, CD45RA, CD71, and CD161(NKRP1A)]. On PND 21, the proportions of splenic CD4+ T cells in the 10-ppm group, activated B (CD45RA+CD71+) cells in the 100- to 1000-ppm groups, and activated T cells (CD3+CD71+) in the 1000-ppm group were significantly decreased, and the population of peripheral CD161+ natural kiler cells on PND 21 and 77 had decreased in the 100- to 1000-ppm groups. In the 1000-ppm group, the serum T3 level was significantly decreased on PND 21 and the serum T4 level was decreased on PND 77. The body, spleen, and thymus weights were not significantly decreased, but liver weight was significantly increased on PND 21 in the 10- to 1000-ppm groups. These results suggest that on PND 21, developmental exposure to the highest dose of DBDE had a weak immunomodulatory effect. Although the most of the immunomodulatory effect had recovered to normal levels on PND 77, a decreasing effect on the natural killer (NK) cell population remained.

Effects of developmental hypothyroidism induced by maternal administration of methimazole or propylthiouracil on the immune system of rats

Methimazole (MMI) and propylthiouracil (PTU) are popularly used antithyroid drugs (ATDs) for the treatment of Graves' hyperthyroidism. The aim of the present study was to determine the effects of ATDs on the developing immune system of the rats.Maternal Sprague–Dawley rats were given drinking water containing 200 ppm of MMI, 12 ppm of PTU (high-dose PTU), or 3 ppm of PTU (low-dose PTU) between gestational day (GD) 10 and postnatal week (PNW) 3. Exposure to the ATDs was ceased upon weaning at PNW3, and the male offspring were sampled at PNWs 3 or 11. The serum thyroid-related hormone levels and the hematological components in the offspring were then determined. The expressions of surface markers in the spleen, thymus and peripheral blood were determined using flowcytometry. The weights of the body, spleen and thymus and the splenic and thymic cell numbers were decreased in the MMI-treated and the high-dose PTU-treated animals at PNWs 3 and 11. The serum levels of thyroid-related hormones were depressed in the MMI and high-dose PTU groups. FACS analysis revealed that the ATDs caused proportional changes in the lymphoid cell subpopulations. The proportion of B cells among the total lymphocytes was significantly decreased at PNW3, whereas that of T cells, especially of inactive T cells, was dramatically increased. Moreover, the proportion of CD4+CD25+ regulatory T cells was significantly increased in the spleen and peripheral blood at PNW3. Most of the above-described changes had recovered to normal levels at PNW11. These results suggest that ATDs might have temporal immunomodulatory effects on the developing immune system.

Modulating effects of dietary fats on methylmercury toxicity and distribution in rats

Fish consumption is the most important source of human exposure to methylmercury (MeHg). Since fish is also a rich source of n − 3 polyunsaturated fatty acids, this study was conducted to examine the effects of dietary fats on MeHg-induced acute toxicity in rats. Weanling male Sprague Dawley rats were administered semi-purified casein-based isocaloric diet containing soy oil, seal oil, docosahexaenoic acid (DHA), fish oil, or lard for 28 days. Rats were then gavaged with 0, 1, or 3 mg MeHg/kg body weight (BW) per day and fed the same diet for 14 consecutive days. On 43rd day of the experiment, rats were sacrificed and blood samples were collected and analyzed for hematology. Liver and spleen were removed, fixed, and examined for pathological changes. Blood, feces, liver, and brain were analyzed for total mercury and/or MeHg contents. Serum samples were analyzed for clinical markers of hepatic injury and immunoglobulin. Total mercury contents in all tissues measured increased with dose. Mercury excretion in feces increased with dose and duration of MeHg treatment. Both diets and MeHg showed significant effects and interacted significantly on many of the toxicological endpoints measured. Many of the effects of MeHg were diet-dependent. For example, in the rats fed the lard diet, 3 mg MeHg/kg BW significantly increased relative liver and spleen weight as compared with vehicle control; whereas in rats fed the fish oil, soy oil, seal oil, or DHA, this effect of MeHg was less obvious or absent, suggesting a protective effect of these diets. MeHg at 3 mg/kg BW significantly decreased serum albumin level in all except DHA dietary groups, implying a protection by the DHA diet on this parameter. Only in the lard dietary group, did 3 mg MeHg/kg BW significantly increase serum bilirubin level, indicating an enhancing effect of this diet on MeHg toxicity. MeHg suppressed the adaptive immune system and stimulated the innate immune system in rats in a diet-dependent fashion. The seal oil diet provided more resistance, while the fish oil diet rendered greater sensitivity to these effects of MeHg on the immune system. These results imply significant modulating effects of dietary fats on MeHg toxicity which may translate into more severe or protective clinical outcomes. Therefore, dietary fats are important factors to be considered in the risk assessment of MeHg exposure.

Acute toxic effects of dioctyltin on immune system of rats

In the present study, dioctyltin chloride (DOTC: 100 mg/kg, BW) was orally administered to immature (30-day-old) male rats, and the acute toxic effects were studied. Di- and monooctyltin (its metabolite) accumulations were mainly detected in the liver, and peaked 48 h later. A similar pattern was also found in the kidney, but the levels were low or trace amounts. Significantly low thymus and spleen weights were detected in DOTC-treated animals. Increased apoptotic cell numbers in the thymus and spleen were observed in DOTC-treated animals also. Although the expression of 97 genes involved in apoptosis was studied in the thymus, at least 24 h after treatment, we could not detect clearly different expressions between DOTC- and vehicle-treated animals. The present results suggest that DOTC was selectively immunotoxic. One of the mechanisms for its immunotoxicity would be via its stimulation of immune cell apoptosis.

The influence of refractory ceramic fibres on pulmonary morphology, redox and immune system in rats

Refractory ceramic fibres (RCF) were studied in male SPRD rats by both in vivo long term sequential and in vitro methods. RCF was administered by single intratracheal instillation and the lungs were examined at the end of months 1, 3 and 6 after exposure. In addition, the direct toxicity of the fibres was examined in a primary culture of alveolar macrophages (AM) and in pneumocytes type II (T2). Pulmonary morphological changes, a number of parameters of the redox system, such as activity of extracellular Cu,Zn/superoxide dismutase (EC-SOD), total glutathione content of the lungs (GSH) and immunoglobulins in bronchoalveolar lavage (IgA, IgG, IgM) and in the blood were measured. The composition of the original RCF and the elemental content of the lung tissue were compared by energy dispersive x-ray analysis (EDXA) before and after exposure. Macrophage alveolitis became confluent and moderate fibrosis developed by the end of month 3, and after 6 months of exposure the intensity decreased to the level of the first month. The RCF did not significantly influence the activity of EC-SOD or the total glutathione content of the lungs. Although aluminium and silicon could be demonstrated by EDXA in the lung tissue at the end of month 3, these elements were no longer detectable by the end of month 6. The RCF decreased IgA significantly in bronchoalveolar lavage (BAL). The main components of RCF induced pulmonary alterations, whereas no significant change could be detected in EC-SOD and GSH. Injuries caused by direct toxicity could be observed in the cell membranes only at the highest concentration. On the basis of these results RCF can be determined as moderately toxic fibres.