Rat White Blood Cells Research Articles

Вплив фітопрепарату BNO 1030 на фагоцитарну активність лейкоцитів крові при цукровому діабеті 1-го типу в щурів

Актуальність. У патогенезі цукрового діабету 1-го типу (ЦД1) і багатьох його ускладнень важливе місце посідають порушення функціональної здатності імунної системи, що є предметом численних досліджень. З огляду на ефективність імуномодулюючої терапії при ЦД1 і його ускладненнях однією з найважливіших проблем є пошук нових ефективних і безпечних імунокоригуючих засобів з високою фармакологічною активністю. Мета дослід­ження: оцінити вплив фітопрепарату BNO 1030 на фагоцитарну активність лейкоцитів крові при ЦД1 у щурів. Матеріали та методи. Експериментальний ЦД1 у щурів індукували шляхом одноразового внутрішньоочеревинного введення стрептозотоцину. Відсоток фагоцитуючих клітин і поглинання макрофагами живих флуоресцентних бактерій у зразках було визначено з використанням флуо­ресцентних живих бактерій Escherichia coli. Результати. На тлі гіперглікемії відбуваються зміни в перерозподілі основних типів лейкоцитів, а саме гранулоцитів і агранулоцитів. Введення препарату BNO 1030 як контрольним, так і діабетичним тваринам приводило до збільшення кількості агранулоцитів, що може свідчити про модулюючий вплив препарату на імунну систему організму тварин. За цих умов знижувалася фагоцитарна активність лейкоцитів: фагоцитарне число в групі хворих на ЦД1 щурів менше ніж на 42 % було знижене порівняно з групою контрольних тварин. Уведення діабетичним щурам препарату BNO 1030 призводило до підвищення фагоцитарного числа на 24 % порівняно з групою діабетичних тварин. Висновки. Зміни супроводжувалися зниженням фагоцитарного індексу як при діабеті, так і при введенні препарату піддослідним групам, що свідчить про порушення в системі неспецифічного клітинного імунітету. Препарат BNO 1030 завдяки його імуномодулюючій дії є ефективним засобом лікування цукрового діабету при його коморбідності з іншими хронічними захворюваннями.

Inhibit of the Virus Infections by using Aromatic Oils, Saccharomyces cerevisiae, Boswellia Carterii and Zinc

Anti-virus treatments are a type of anti-microbiology, a class that includes antibiotics and anti-microbiological drugs, including fungi. These treatments were relatively harmless to the host, so they can be used to treat patients. Therefore, it must distinguish between the anti-viral drug and its killer, which is not considered a drug category, but rather destroys the virus body outside the living cell. Most antiviral drugs currently available help in the treatment of immune deficiency disease in patients. The results showed significant differences between influenza vaccinated animals with diet therapy with inhaling essential oils, and non-vaccinated with absent of diet therapy and inhaling essential oils for the percentages from differential number of white blood cells in rats. The results showed a clear rise in the differential number of leukocytes in the blood samples of the experiment animals that were fed on yeast (Saccharomyces cerevisiae) enriched with lemon oil, and zinc, in addition to chewing gum. The white blood cell count was calculated during fixed periods 2, 8 and 10 days from vaccinated with influenza virus for all experiment animals, the results were (53, 96, 9, 7) for (Neutrophil, Lymphocyte, Monocyte and Eosinophil) sequentially, after 2 days, (46, 92, 8, 5) for (Neutrophil, Lymphocyte, Monocyte and Eosinophil) sequentially, after 8 days, and (42, 85, 7, 4) for (Neutrophil, Lymphocyte, Monocyte and Eosinophil) sequentially, after 10 days, of the test group fed on yeast enriched with lemon oil, zinc, and chewing gum, and then it was vaccinated, compare between control group. There were no clear symptoms for experimental animals with influenza vaccine (effective and not weakened) that was fed to the food above and inhaled eucalyptus oil with a clear increase in the number of white blood cells compared to the control group and the negative group for feeding. While the symptoms were clear on the negative control group (not to use diet therapy) and vaccinated with effective influenza vaccine. The diet therapy was prepared from a group of effective essential oils, which were used in two ways, the first was through direct inhalation, that consist of (25 ml of oil eucalyptus, 25 ml of oil lemon and 100% oxygen gas) by heat, which third frequency of use in the one day for 10 days. The second components used by mouth that consist of (25 ml/kg oil lemon, 5µg/kg zinc, 8 mg/kg Saccharomyces cerevisiae, and 5 mg/kg chewing gum (Boswellia Carterii), which third frequency of use in the one day for 10 days. In this way, we increase immunity and prevent the virus from binding to the cell by inhibiting an enzyme angiotensin-converting enzyme 2.

Comparative studies on endogenic stress hormones, antioxidant, biochemical and hematological status of metabolic disturbance in albino rat exposed to roundup herbicide and its active ingredient glyphosate.

There have been growing concerns and uncertainty about reports attributing the metabolic disturbance induced by a commercial formulation of glyphosate-based herbicide to its active ingredient. We therefore compared the effects of Roundup Original® and its active ingredient glyphosate on some hypothalamic-pituitary-adrenal (HPA) hormones and oxidative stress markers, biochemical and hematological profiles in 56 adult male albino rats randomly assigned to seven treatments of eight rats per treatment. The rats were orally exposed to Roundup Original® and its active ingredient daily at 3.6mg/kg body weight (bw), 50.4 and 248.4mg/kgbw of glyphosate equivalent concentrations for 12weeks, while control treatment received distilled water. Serum concentrations of corticosterone, adrenocorticotropic hormone, aldosterone and concentration of oxidative stress marker, biochemical and hematological profiles in the blood were determined. Concentrations of corticosterone and aldosterone were significantly higher (p < 0.05) in rats treated with Roundup in a dose-dependent manner. Reduced glutathione concentration, catalase, and butyrylcholinesterase activities reduced significantly in rats treated with Roundup relative to those treated with the active ingredient. Lipid peroxidation was observed in rats treated with Roundup. Biochemical and hematological profiles of rats treated with Roundup were significantly altered (p < 0.05). However, significant changes in only acid phosphatase, lactase dehydrogenase, bilirubin, and white blood cells in rats treated with the active ingredient at 50.4mg/kg were observed. The severe metabolic disturbance and stress observed in rats treated with the commercial formulation of Roundup herbicide may not be associated with the mild changes induced by the active ingredient.

Клеточный состав белой крови крыс при физической нагрузке разной интенсивности

Клеточный состав белой крови крыс при физической нагрузке разной интенсивности

Anti-inflammatory effect and the effect on acute pharyngitis rats model of compound Lobelia oral liquid.

ObjectiveObserve anti-inflammatory effect and the effect on acute pharyngitis rats model induced by ammonia water of compound Lobelia oral liquid, providing experimental basis for its clinical use.MethodsUse egg white establish foot swelling rats model and use carboxymethyl cellulose establish white blood cell migration rats model. Then observe the anti-inflammatory effect of compound Lobelia oral liquid. Use 15% ammonia spray at pharyngeal establish acute pharyngitis rats model, Visual observation and conduct grading of pharyngeal tissue stimulation in rats, measure the levels of TNF-α and IL-6 in serum. Pharyngeal tissue was taken to observe the morphological changes.ResultAll dose groups of compound Lobelia oral liquid can reduce the rate of foot swelling of rats at all time points (P < 0.01 or P < 0.05), and significantly reduce the number of white blood cells of rats (P < 0.01); And improve the local hyperemia degree, reduce secretion, reduce local swelling of pharyngeal tissue, reduce the serum TNF-α and IL-6 levels of acute pharyngitis rats with different degrees (P < 0.01 or P < 0.05).ConclusionCompound Lobelia oral liquid has a good anti-inflammatory effect on foot swelling and white blood cell migration rats model, as well as significant improvement effect on acute pharyngitis rats model.

The effects of strawberry tree water leaf extract, arbutin and hydroquinone on haematological parameters and levels of primary DNA damage in white blood cells of rats

Ethnopharmacological relevanceStrawberry tree (Arbutus unedo L., Ericaceae) leaves represent a potent source of biologically active compounds and have been used for a long to relieve symptoms of various health impairments and diseases. Two major compounds related to their beneficial activities in animals and humans are arbutin and hydroquinone. Aim of the studyTo establish potential benefit/risk ratio associated with daily oral administration of strawberry tree water leaf extract, arbutin and hydroquinone in doses expected to be non-toxic. Materials and MethodsWe performed a 14-day and a 28-day study on male and female Lewis rats and evaluated main haematological parameters and the effects of treatments on the levels of primary DNA damage in white blood cells (WBC) using the alkaline comet assay. ResultsOur findings suggest no significant changes in the haematological parameters following prolonged exposure to strawberry tree water leaf extract, arbutin, and hydroquinone. However, hydroquinone causes increased, and extract as well as arbutin decreased WBC count in male rats compared to control after 14 days of treatment. DNA damage measured in WBC of rats treated with all compounds was below 10% of the DNA in the comet tail, which indicates low genotoxicity. The genotoxic potential of strawberry water leaf extract was within acceptable limits and reflected effects of a complex chemical composition upon DNA. We also observed slight gender- and exposure time- related differences in primary DNA damage in the leucocytes of control and treated rats. ConclusionsFuture studies should investigate which doses of strawberry tree water leaf extract would be most promising for the potential use as a substitute for bearberry leaves for treatment of urinary infection.

Mitigation of heat stress-related complications by a yeast fermentate product

Heat stress results in a multitude of biological and physiological responses which can become lethal if not properly managed. It has been shown that heat stress causes significant adverse effects in both human and animals. Different approaches have been proposed to mitigate the adverse effects caused by heat stress, among which are special diet and probiotics. We characterized the effect of the yeast fermentate EpiCor (EH) on the prevention of heat stress-related complications in rats. We found that increasing the body temperature of animals from 37.1±0.2 to 40.6±0.2°C by exposure to heat (45°C for 25min) resulted in significant morphological changes in the intestine. Villi height and total mucosal thickness decreased in heat-stressed rats pre-treated with PBS in comparison with control animals not exposed to the heat. Oral treatment of rats with EH before heat stress prevented the traumatic effects of heat on the intestine. Changes in intestinal morphology of heat-stressed rats, pre-treated with PBS resulted in significant elevation of lipopolysaccharides (LPS) level in the serum of these animals. Pre-treatment with EH was effective in the prevention of LPS release into the bloodstream of heat-stressed rats. Our study revealed that elevation of body temperature also resulted in a significant increase of the concentration of vesicles released by erythrocytes in rats, pre-treated with PBS. This is an indication of a pathological impact of heat on the erythrocyte structure. Treatment of rats with EH completely protected their erythrocytes from this heat-induced pathology. Finally, exposure to heat stress conditions resulted in a significant increase of white blood cells in rats. In the group of animals pre-treated with EH before heat stress, the white blood cell count remained the same as in non-heated controls. These results showed the protective effect of the EH product in the prevention of complications, caused by heat stress.

Tetrahydroxylated-benzo[a]pyrene isomer analysis after hydrolysis of DNA-adducts isolated from rat and human white blood cells

Since exposure to benzo[a]pyrene is suspected to be associated with several health issues, significant efforts have been made to develop efficient strategies for the assessment of human exposure to this ubiquitous compound. In this context, a method was developed for the analysis of four tetrahydroxylated-benzo[a]pyrene isomers resulting from the hydrolysis of their respective diol-epoxide precursors which are involved in DNA-adduct formation. The analytical sensitivity necessary to reach environmental levels of concentration was obtained by using gas chromatography–tandem mass spectrometry. The recovery determined at the four concentration levels were estimated in average at 83% for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±), 29% for benzo[a]pyrene-r-7,t-8,t-9,t-10-tetrahydrotetrol(±), and 82% for benzo[a]pyrene-r-7,t-8,C-9,c-10-tetrahydrotetrol(±). The coefficient of determination of the calibration curve was above 0.997 for all the analytes investigated and the limit of quantification ranged from 0.5 to 2 adduct/108 nucleotides. The precision was between 5.3% and 22.3%. The suitability of the method was firstly evaluated by the analysis of DNA isolated from white blood cells of rats submitted after controlled exposure to benzo[a]pyrene. The four targeted tetra-OH-benzo[a]pyrenes as well as two unknown isomers were detected in all the treated animals. Benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol(±) appeared as the most abundant isomer in both treated and control animals followed by benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±). The method was afterwards applied to the analysis of DNA isolated from white blood cells of human volunteers. The results confirmed that this method was sufficiently sensitive to monitor environmental levels of exposure since all the specimens analyzed were above the limit of quantification for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±) and two of them were positive for benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol(±), thereby highlighting interspecies differences in the nature of the tetrahydroxylated-benzo[a]pyrene isomers formed. This study confirms the necessity to focus on all the tetrahydroxylated-benzo[a]pyrene isomers, which could be indicators of benzo[a]pyrene-associated toxicity related to an individual's own metabolism, rather than limit to a single form.

Tetrahydroxylated-benzo[a]pyrene isomer analysis after hydrolysis of DNA-adducts isolated from white blood cells

On the assumption of associations between exposure to benzo[a]pyrene and certain health disorders, several recent research studies have been dedicated to the development of strategies aimed at assessing human exposure to this ubiquitous pollutant. As part of these research efforts, a method was designed for the analysis of four tetrahydroxylated-benzo[a]pyrene isomers resulting from the hydrolysis of their respective diol-epoxide precursors which are involved in DNA-adduct formation. The analytical sensitivity necessary to reach environmental levels of concentration was obtained by means of gas chromatography–tandem mass spectrometry. The suitability of the method was firstly evaluated by the analysis of DNA isolated from white blood cells of human volunteers. The results obtained confirm that this method was sufficiently sensitive to detect environmental exposure levels as all the samples measured were above the limit of quantification for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±) and two of them tested positive for benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol(±). The method was subsequently applied to the analysis of DNA isolated from white blood cells of rats submitted to benzo[a]pyrene-controlled exposure. The study led to the detection of the four targeted tetra-OH-benzo[a]pyrenes as well as of two unknown isomers in all benzo[a]pyrene-treated animals. Interestingly, benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol(±) proved to be the most abundant isomer in both treated and control animals, followed by benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±); which points out to interspecies differences in the nature of the tetrahydroxylated-benzo[a]pyrene isomers formed. These results highlight the need to focus on all the tetrahydroxylated-benzo[a]pyrene isomers, which could be indicators of benzo[a]pyrene-associated toxicity related to an individual's own metabolism, rather than limit to a single form.

In vivo evaluation of cholinesterase activity, oxidative stress markers, cyto- and genotoxicity of K048 oxime–a promising antidote against organophosphate poisoning.

K048 is a member of K-oximes, a new oxime class that has recently been confirmed effective against poisoning by the nerve agent tabun and several pesticides. The toxicity profile of the K048 oxime has not been fully characterized and its optimal therapeutic dose has not yet been established. Earlier studies report excellent results with K048 in reactivating tabun-phosphorylated AChE and in the therapy of tabun-poisoned mice. It possesses a low acute toxicity and exerts an acceptable toxicity profile on isolated human peripheral blood lymphocytes in vitro. Intraperitoneal administration of K048 in rats resulted in an LD50 of 238.3 mg/kg. In this in vivo study, we investigated cholinesterase (ChE) activity and oxidative stress marker levels (lipid peroxidation and superoxide dismutase activity) in the plasma of exposed rats after administering the compound at 25% of its LD50. Lymphocyte viability was evaluated using an acridine orange/ethidium bromide in situ fluorescent assay. The levels of primary DNA damage in rat white blood cells were measured using the alkaline comet assay. The compound applied at 25% of its LD50 did not significantly affect ChE activity and lipid peroxidation and did not cause significant changes in the SOD activity in plasma. The cytotoxicity profile of K048 in the tested dose was also acceptable, and it did not possess significant DNA-damaging potential. The obtained results are promising for further evaluations of the K048 oxime, which should include tests on a broader concentration range and longer incubation times.

Вплив тривалого введення CdCl2 щурам на показники лейкопоезу

It was shown that long-term (7 and 21 day) administration of CdCl 2 (3 mg/kg) increases the number of white blood cells in rats appropriately for 57.3% and 38.5%, these changes we are mediated by 54.7% increase of the content of polymorphonuclear granulocytes. Analysis of the dynamics of cells of leukopoiesis system under the influence of CdCl 2 indicates that decreased monocytes content results in a decrease of number of agranulocytes in rats’ blood. Thus, in animals, exposed to long-term influence of CdCl 2 ,the stage of antigen presentation might occur less effective due to a diminished number of macrophages. Such effect, together with a decrease of leukocytes content, could impair the immune defense in treated animals. Keywords : leukocytes, cadmium, neutrophilic granulocytes.

Single administration effects of ethanol on the distribution of white blood cells in rats

Acute single administration effects of ethanol on the distribution of total white blood cells (WBCs), neutrophil, basophil, eosinophil, monocyte and lymphocytes were studied in rats. Acute single administration effects of ethanol on the number of red blood cells (RBCs), hemoglobin concentration and hematocrit were also examined. Male 8-week-old Sprague Dawley rats were randomly divided into the ethanol-administered (ETA) group and the control (CON) group. Two parts of an experiment, 1) 1st experiment : (ethanol dose : 1.0 g/kg body weight), and 2) 2nd experiment : (ethanol dose : 2.0 g/kg body weight) were carried out in rats. The rats were starved to 19:00, and deprived of diet for 12 hr and water for 1 hr before the single administration of ethanol. 1.0 or 2.0 g/kg body weight of ethanol (in 20% (w/w) ethanol) was orally administered to ETA group rats via a stainless stomach tube. In the CON group rats, 0.9% NaCl solution was orally given with the solution volume being equal, in the same manner. Single administration of 1.0 or 2.0 g/kg body weight of ethanol did not change the number of RBCs, hemoglobin concentration and hematocrit. Single administration of 1.0 g/kg body weight of ethanol did not also change the number of WBCs. However, administration of 2.0 g/kg body weight of ethanol increased significantly the number of neutrophil, basophil, monocyte and total WBCs without changing the number of eosinophil and lymphocytes. These results suggest that single administration of 2.0 g/kg body weight of ethanol to rats increased markedly the number of the natural immunity cells without changing the number of acquired cells.

Acute and Subacute Effects of Dexamethasone on the Number of White Blood Cells in Rats

The purpose of this study was to elucidate the effects of dexamethasone, a synthetic glucocorticoid, on the immune system by analyzing the number of white blood cells (WBCs) over the course of hours and days of dexamethasone administration. Dexamethasone was given as either a single dosage [1.0 mg/kg body weight (BW); subcutaneous injection (s.c.)] or as a daily dosage (1.0 mg/kg BW per day; s.c.) for 10 days for the hourly and daily assessment of changes in the number of white blood cells, respectively. A single administration of dexamethasone markedly decreased the number of total WBCs, as well as the number of lymphocyte, monocyte, neutrophil and eosinophil subsets with a nadir at 8 hr post-injection. The number of these cells recovered to the control levels at 24 hr. The numbers of total WBCs, lymphocytes, monocyte, eosinophil and basophil were reduced by the daily administration of dexamethasone. However, the number of neutrophil was significantly higher at days 2 and 8 after the injection. These results suggest that glucocorticoid-mediated immunosuppressions are at least partly attributable to quantitative changes in the number of circulating WBCs.

Subacute Effects of Capsaicinoids on the Distribution of White Blood Cells in Rats

The subacute effects of dihydrocapsaincin (DHC) and capsaicin (CAP) (dose=3 mg/kg body weight per day for 10 days, subcutaueous) on the number and distribution of white blood cells (WBCs) were studied in male adult rats. The administration of DHC and CAP for 10 days decreased significantly the number of total WBCs, lymphocytes and monocyte, and increased significantly the number of the neutrophil and eosinophil without changing the number of basophil. The administration of DHC significantly decreased thymus weight and increased adrenal weight, showing that DHC induced thymus atrophy and adrenal hypertrophy. These results suggest that capsaicinoids induced the decrease of acquired immunity responses and these phenomena may have in part participated in capsaicinoids-induced stress-responses in rats.

Allyl isothiocyanate-induced changes in the distribution of white blood cells in rats

The main pungent component of wasabi (Eutrema japonica) is known to be isothiocyanate and its derivatives, volatile substances. Allyl isothiocyanate (AITC) accounts for more than half of isothiocyanate derivatives. However, there is a little information on the effects of AITC on the immune system by analyzing the number of white blood cells (WBCs) over the course of days of AITC administration. In the present study, we studied the effects of AITC (dose=20 mg/kg body weight/day for 10 days, subcutaneous: s.c.) on the number of WBCs (total WBCs, lymphocytes, monocyte, neutrophil, basophil and eosinophil) and plasma corticosterone concentrations in adult male rats. Administration of AITC decreased significantly the number of total WBCs on days 1-4 post s.c. injection by 25-27%. Administration of AITC also decreased the number of lymphocytes on days 1-10 by 21-36% and monocyte on days 1-8 by 28-78%. However, administration of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC did not change the number of eosinophil and basophil. Plasma corticosterone concentrations during the experimental period were 4.7-8.4 times significantly higher in the AITC group than in the control group, indicating that AITC induced stress-responses. The relative weights of thymus and adrenals per body weight were significantly lower and clearly higher in the AITC group than in the control group, respectively. These results suggest that AITC-mediated stress-responses are at least in part attributable to changes in the number of circulating WBCs.

Acute Effects of Dihydrocapsaicin and Capsaicin on the Distribution of White Blood Cells in Rats

The acute effects of dihydrocapsaicin (DHC) and capsaicin (CAP) on the number of white blood cells (WBCs), neutrophils, eosinophils, basophils, monocytes, lymphocytes, T lymphocytes, B lymphocytes and NK cells, and serum corticosterone levels were studied in rats. Male 7-wk-old SD rats were divided into DHC (3.0 mg/kg BW), CAP (3.0 mg/kg BW) and control (CON) groups. The number of total WBCs was 1.30-1.42 times significantly higher in the DHC group than in the CON group at 6-12 h. The number of neutrophils was 1.62 times significantly higher in the DHC group than in the CON group at 12 h. The number of total WBCs and neutrophils, however, showed no significant changes between the CAP and CON groups. The number of lymphocytes was 0.61 and 0.70 times significantly lower in the DHC and CAP groups than in the CON group at 3 h. The number of T lymphocytes and B lymphocytes was 0.74 and 0.54 times lower in the DHC group than in the CON group, respectively. CAP, however, did not significantly change the number of T lymphocytes or B lymphocytes. No significant changes in the number of NK cells were observed among the three groups. CAP and DHC did not change the number of monocytes, eosinophils or basophils. No significant changes of the serum corticosterone levels were observed among the three groups. In conclusion, capsaicinoids decreased the number of acquired immunity cells, and increased the number of total WBCs and neutrophils without changing the number of monocytes, eosinophils or basophils. The magnitude of these effects was relatively higher in DHC than in CAP.

Zinc-Deficiency Induced Changes in the Distribution of Rat White Blood Cells

Zinc is known to play an important role for immune-functions. However, the effects of zinc-deficiency on the immune response system from the point of view of the distribution changes of the number of total white blood cells (WBCs) are still primarily unknown. Therefore, the effects of zinc-deficiency on the number of total WBCs, neutrophil, eosinophil, basophil, monocyte and lymphocytes (T lymphocyte, B lymphocyte and NK cell) were studied in rats. The weaned male rats were randomly divided into the zinc deficient diet (ZDD: 0.7 mg zinc/kg diet) group and the control diet (CON: 34.8 mg zinc/kg diet) group, and were pair-fed for 4 wk. The number of lymphocyte subsets, visceral organ weights, serum zinc, corticosterone and IL-6 concentrations were also determined. Zinc-deficiency increased duration-dependently the number of total white blood cells, granulocytes (neutrophil, eosinophil and basophil) and monocytes in 2-4 wk without changing the number of lymphocytes, T lymphocytes, B lymphocytes or NK cells. The relative weights of thymus and adrenals were 0.63 times (p<0.01) lower and 1.60 times (p<0.001) higher in ZDD group than in CON group, respectively. Zinc-deficiency increased serum corticosterone concentration to 1.48 times (p<0.05) without changing serum IL-6 concentration, as compared with those of CON group. From these results, zinc-deficiency increases markedly the number of granulocytes and monocytes without changing the number of lymphocytes, T lymphocytes, B lymphocytes or NK cells. These results also suggest that zinc-deficiency induces stress responses and the responses may have in part participated in increased actions of the number of granulocytes and monocytes during zinc-deficiency, and induce thymus atrophy and adrenal hypertrophy.

Capsaicinoid-induced changes in the number of white blood cells in rats

Capsaicinoid-induced changes in the number of white blood cells in rats

Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

Aim:In this study, we employed chimeric human/mouse Proteinase 3 (PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice.Method:Rats and mice were immunised with recombinant...

Importance of DNA-Adduct Formation and Gene Expression Profiling of Disease Candidate Genes in Rats Exposed to Bitumen Fumes

The equivocal experimental and epidemiological evidence of bitumen fumes and the possible mechanisms of toxicity remain uncertain. This study therefore aimed at investigating the genotoxicity of bitumen fumes, the biotransformation and urinary excretion of PAHs, and altered expression of a selected number of genes in lung, nasal epithelium, and white blood cells of rats. Animals were exposed to three different concentrations (low: 4 mg/m 3 ; medium: 20 mg/m 3 ; high: 100 mg/m 3 ) of bitumen fume condensate for 5 days, 30 days, and 12 months (6 hours per day) or ambient air. Notably, no dose-related signs of intolerance were observed throughout the inhalation period but dose dependent uptake of bitumen fumes was observed based on urinary excretion of PAHs and metabolites. At best, measurements of naphthols enabled an estimate of dose-dependent body burden. Excretion of 1-hydroxy- and 2-hydroxyphenanthrene was dose dependent and their production is catalyzed by the CYP1A1 monooxygenase which we found to be strongly induced upon exposure to bitumen fumes. Furthermore, pyrene, a minor component in bitumen fumes, produced hydroxypyrene levels close to the detection limit in rat urine. We additionally determined DNA adduct formation by the 32 P-postlabelling assay and observed a dose and time dependent increase of 3 to 4 stable DNA adducts in lung, nasal, and alveolar epithelium. DNA adduct levels were highest in nasal epithelium, the relative adduct level (RAL) being 450 adducts per 10 9 nucleotides. For lung and alveolar epithelium the RAL was 114 and 76 adducts per 10 9 nucleotides, respectively. However, we did not observe micronucleated red blood cells of the peripheral blood or with polychromatic erythrocytes of the bone marrow (after 12 months). It is important to note that erythrocyte cell count in bone marrow smears was reduced in four out of six animals after 12 months of exposure, clearly demonstrating that components of bitumen fume had reached the bone marrow. Finally, we investigated by reverse transcription polymerase chain reaction regulation of genes with known functions in inflammation, asthma and other pulmonary diseases. Gene expression changed during the time of exposure. With the monooxygenases CYP1A1 and CYP2G1 we observed dose dependent regulation in nasal and lung tissue. We also observed significant, but dose independent, regulation of cathepsin K and D, cadherin 22, platelet activating factor acetylhydrolase isoform 1b alpha subunit and the regulator of G-protein signalling in nasal epithelium of male rats after exposure to bitumen fumes. We found bitumen fumes to be genotoxic in target tissue of exposure and observed altered regulation of genes involved in the metabolic activation of polycyclic aromatic hydrocarbons and cellular inflammatory processes. These findings are consistent with the histopathology observed in the respiratory tract of rats chronically exposed to bitumen fume. An understanding of the regulation of suspected disease candidate genes in target tissues of exposure will be an interesting objective for further research into the mechanisms of toxicity.