Efficacy of tea polyphenols (TP 50) against radiation-induced hematopoietic and biochemical alterations in beagle dogs.

OBJECTIVE: To investigate the radioprotective effect of tea polyphenols (TP 50) against radiation-induced organ and tissue damage. METHODS: Beagle dogs were exposed to a single acute dose of whole-body γ-radiation (3 Gy) and orally administered TP 50 (80 or 240 mg·kg－1·d－1) for 28 consecutive days. A hemogram was obtained from experimental dogs every other day for 42 d. At the end of the experiment, enzyme activities of the antioxidants superoxide-dismutase andglutathione peroxidase, serum levels of inflamma- tory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6), colony-forming units of bone marrow hematopoietic progenitor cells, andorgan coefficients were measured. RESULTS: Dogs exposed to γ-radiation alone exhibited typical hematopoietic syndrome. In contrast, irradiated dogs that received TP 50 exhibited an improved blood profile with reduced leucopenia, thrombocytopenia (platelet counts), and reticulocyte levels. TP 50 also significantly elevated levels of the endogenous antioxidant enzyme superoxide-dismutase, reduced the increased levels of serum cytokine in response to radiation-induced toxicity, and increased colony-forming units of bone marrow hematopoietic progenitor cells. In addition, TP 50 repaired radiation-induced organ damage. CONCLUSION: The current findings suggest that oral administration of TP 50 to beagle dogs effectively alleviated hematopoietic bone marrow dam- age induced by γ-radiation.

Effects of nanocrystalline PbSe on hematopoietic system and bone marrow micronucleus rate of rats.

OBJECTIVE: To investigate the effect of lead selenide nanocrystals on hematopoietic system and bone marrow micronucleus rate of rats. METHOD: Specific pathogen free SD rats were randomly divided into 4 groups (8 rats in each group), and injected with of 0 (control group), 10 (low dose group), 20 (middle dose group), 30 mg/kg (high dose group) nanocrystalline PbSe, respectively. Seven weeks after injection, the blood was taken from rats for routine index detection; the number of micronucleus cells per 1000 polychromatic erythrocyte from bone marrow was counted. RESULTS: White blood cell (WBC), lymphocyte (LYM) count in low dose group rats, and WBC, LYM, granulocyte (GRN), monocytes (MOD) counts in high dose group significantly increased compared to those of control group. LYM% ratio decreased while GRN% ratio increased along with the increase of exposure dosage. Compared with those of the control group, levels of erythrocyte mean corpuscular volume (MCV) in low dose group, hemoglobin (HGB), red blood cell specific volume (HCT), MCV in middle dose group and red blood cell (RBC), HGB, HCT, MCV in high dose group, were markedly decreased. Red blood cell distribution width (RDW), blood platelet (PLT) levels in three exposure groups of were higher than those in control group. Marrow micronucleus test results showed that, the micronucleus rate rise in mid dose and high dose group compared with the control group, suggesting that nanocrystalline PbSe has genetic toxicity on rats. CONCLUSIONS: Nano PbSe can lead to changes in blood routine index and bone marrow micronucleus rate, and its toxicity was positively related to the dosage.

Polysaccharide isolated from Parmelia tinctorum ameliorates ionizing irradiation-induced damage in mice.

In this study, WPT-A, a type of water-soluble homogeneous lichen polysaccharide, was isolated and purified from Parmelia tinctorum. We investigated whether WPT-A has radioprotective effects when administered before total-body irradiation (TBI). Mice were treated with WPT-A via intraperitoneal injection (i.p.) once per day for three consecutive days prior to 7, 7.5, 8.5, 10 or 10.5-Gy TBI. Our results indicated that the survival rate was enhanced at a range of levels of TBI. The calculated dose reduction factor (DRF) was 1.2. White blood cell (WBC) counts, spleen colony forming units (CFU-S) and bone marrow nucleated cell (BMNC) counts were used to investigate the radioprotective effects of WPT-A on the hematopoietic system. The treatment groups received WPT-A at 20, 50 and 80 mg/kg b.w. doses before 6.5-Gy TBI and showed significantly higher BMNC and WBC counts compared with the radiation-only group. The groups administered 50 and 80 mg/kg b.w. WPT-A showed a significant increase in CFU-S compared with the radiation-only group. We also carried out a single cell gel electrophoresis assay to explore the radioprotective effects of WPT-A on DNA damage. The results from single-cell gel electrophoresis of peripheral blood leukocytes showed that WPT-A attenuated radiation-induced DNA damage. These results indicate a potential use for WPT-A as a radioprotector.

Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice.

The aim of this work was to delineate the effects of chronic ingestion of strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l(-1) of (90) Sr two weeks before mating. Offspring were then continuously contaminated with (90) Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20 weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in (90) Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C-telopeptide of collagen in the plasma of (90) Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of (90) Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis.

Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes.

NOD2 functions as an intracellular sensor for microbial pathogen and plays an important role in epithelial defense. The loss-of-function mutation of NOD2 is strongly associated with human Crohn's disease (CD). However, the mechanisms of how NOD2 maintains the intestinal homeostasis and regulates the susceptibility of CD are still unclear. Here we found that the numbers of intestinal intraepithelial lymphocytes (IELs) were reduced significantly in Nod2(-/-) mice and the residual IELs displayed reduced proliferation and increased apoptosis. Further study showed that NOD2 signaling maintained IELs via recognition of gut microbiota and IL-15 production. Notably, recovery of IELs by adoptive transfer could reduce the susceptibility of Nod2(-/-) mice to the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Our results demonstrate that recognition of gut microbiota by NOD2 is important to maintain the homeostasis of IELs and provide a clue that may link NOD2 variation to the impaired innate immunity and higher susceptibility in CD.

Effect of mycophenolate mofetil on hematological side effects incidence in renal transplant recipients.

Mycophenolate mofetil (MMF), an immunosuppressant administered after solid organ transplantation, is generally well tolerated; however, it frequently causes hematological toxicity. In this study, we aimed to assess the relation between the pharmacokinetic parameters of MMF metabolites (mycophenolic acid [MPA] and 7-O-MPA glucuronide [MPAG]) and the adverse effects on the hematopoietic system in renal transplant recipients. The four-h pharmacokinetic profiles of MPA and MPAG were determined using the HPLC method for MMF-treated patients (n = 61) among 106 renal transplant recipients (during the late post-transplant period) participating in the study. Anemia was more frequently observed in the study group compared with the control group (30.7% vs. 20.0%) and although the difference was insignificant, plasma iron concentrations were significantly higher in patients treated with MMF (32.9 ± 9.4 µmol/L vs. 28.7 ± 9.4 µmol/L; p = 0.032). Iron supplementation was more frequently applied to patients with anemia (48.2%) compared with patients with hemoglobin within the norm (20.3%; p = 0.005). As all MPAG pharmacokinetic parameters correlated negatively with hemoglobin and hematocrit, and MPAG pharmacokinetic parameters were higher in patients with anemia, MPAG may be the predicting factor of MMF side effects. In renal transplant recipients, especially with deteriorated renal function, extensive iron supplementation may be ineffective as anemia was associated with declined renal function and was not caused by low iron concentration.

Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats.

Litsea elliptica Blume has been traditionally used to treat headache, fever, and stomach ulcer, and has also been used as an insect repellent. The acute and subacute toxicities of L. elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats. For the acute toxicity study, L. elliptica essential oil was administered in doses from 500 to 4000 mg/kg (single dose), and in the subacute toxicity test, the following doses were used: 125, 250, and 500 mg/kg, for 28 consecutive days. In the acute toxicity study, L. elliptica essential oil caused dose-dependent adverse behaviours and mortality. The median lethal dose value was 3488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg. The subacute toxicity study of L. elliptica essential oil did not reveal alterations in body weight, and food and water consumptions. The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined, except for the hemoglobin, mean cell hemoglobin concentration, mean cell volume, mean cell hemoglobin, serum albumin, and serum sodium. However, these differences were still within the normal range. No abnormalities or histopathological changes were observed in the liver, pancreatic islet of Langerhans, and renal glomerulous and tubular cells of all treated groups. In conclusion, L. elliptica essential oil can be classified in the U group, which is defined as a group unlikely to present an acute hazard according to World Health Organization (WHO) classification.

[In vivo and in vitro effect of peptide HP-6 derived from donkey serum albumin on hematopoietic system].

OBJECTIVE: By bioinformatics method, the effect in hematopoietic system of bioactive peptide HP-6, which was obtained from donkey serum albumin and is one of the major protein components from donkey-hide gelatin, was investigated. METHOD: Human bone marrow nucleated cells (hBMNCs) and murine bone marrow stromal cells (mBMSCs) were separated and cultured with different concentration of peptide HP-6 (0.000 15, 0.001 5, 0.015, 0.15, 1.5 micromol x L(-1)). The effect on promoting proliferation of cells related to hematopoiesis in bone morrow was detected and the ultrastructure of cells after treated by HP-6 was observed through transmission electron microscope. Hemorrhage anemia mouse model and anemia mouse model induced by cyclophosphamide were established, and randomly divided into peptide HP-6 groups which were administered respectively with different doses (1, 0.1, 0.01 mg x kg(-1)) by gavage, and control group which was administered with PBS by gavage. Peripheral blood components of all mice and bone morrow cells (BMC) number of mice induced by cyclophosphamide were evaluated. RESULT: Peptide HP-6 could concentration-related promote the proliferation of hBMNCs and mBMSCs, hBMNCs got the highest reproduction rate of 152.11% and mBMSCs also got 63.52% with the concentration of 0.15 micromol x L(-1), then the reproduction rate decreased while the concentration kept increasing. The transmission electron microscope showed that ultrastructure of cells was normal after treated by HP-6.1 mg x kg(-1) peptide HP-6 significantly increased peripheral platelet and protected mouse morrow injured by cyclophoshamide. 0.1 mg x kg(-1) peptide HP-6 significantly increased peripheral platelet with relative growth rate of 77.65%, increased peripheral white blood cells count and peripheral red blood cells count, also could protect mouse peripheral blood after treated by chemotherapeutics. CONCLUSION: Peptide HP-6 could promote the proliferation of cells related to hematopoietic system, enhance mouse hemopoiesis function and the resistance to chemotherapeutic injury.

Radioprotection of Swiss albino mice by Prunus avium with special reference to hematopoietic system.

Prunus avium (family Rosaceae) has been used ethnomedicinally for the treatment of many diseases,but its radioprotective efficacy has hardly been explored. Presence of high anthocyanin content and phenolic compound with good antioxidative capacity has been reported by researchers. Its radioprotective effect against 5, 7, 10, and 12 Gygamma radiation was evaluated by 30 day survival assay. Regression analysis yielded LD(50/30) 5.81 and 9.43Gy for irradiated only and (P. avium fruit extract) PAE + radiation groups, respectively. The dose reduction factor was computed as 1.62. For biochemical and hematological studies, Swiss albino mice were divided into four groups: (i) control (vehicle treated), (ii) PAE treated (450 mg kg/day for 15 consequetive days), (iii) irradiated (5 Gy), and (4) PAE + irradiated. The irradiation of animals resulted in a significant elevation of lipid peroxidation and depletion in glutathione and protein levels in blood serum and spleen, which could be significantly checked by administration of PAE. Radiation-induced deficit in blood sugar, cholesterol, and hematological constituents could also be modulated by supplementation of PAE before and after irradiation. The possible prophylactic and therapeutic action noted by P. avium against radiation induced metabolic disorders may be due to synergistic action of various antioxidants, minerals, vitamins, etc., present in the fruit. Further mechanistic studies aimed at identifying the role of major ingredients in the extract are needed.

Protective role of tea polyphenols in combination against radiation-induced haematopoietic and biochemical alterations in mice.

The purpose of this study was to investigate the radioprotective effects of tea polyphenols (TPs) in various combinations against radiation-induced damage in mice. Mice were divided into different groups: non-irradiated control, irradiated control, amifostine (43.6 mg/kg, i.v. 30 min before irradiation; positive control) and various combinations of tea polyphenols in different doses. The radioprotective effect on the haematopoietic system, serum cytokines and endogenous antioxidant enzymes were studied. TP50, containing approximately 50% of (-)-epigallochatechin-3-gallate in addition to other catechins, showed the greatest radioprotective effect against radiation-induced changes in haematological parameters (red blood cell count, white blood cell count and haemoglobin), and maintained the spleen and thymus indices unchanged (spleen or thymus weight/body weight × 1000). Tea polyphenols also significantly decreased radiation-induced lipid peroxidation (malondialdehyde levels), elevated endogenous antioxidant enzymes (superoxide dismutase) and reduced the serum cytokines which were elevated in radiation-induced toxicity. This evidence shows the potential of tea polyphenols, particularly in the combination found in TP50, as radioprotectors in mice, especially regarding recovery of the haematopoietic system, antioxidant potential activity and reduction of inflammatory cytokines.

Comparative investigations on the protective effects of rhodioside, ciwujianoside-B and astragaloside IV on radiation injuries of the hematopoietic system in mice.

The aim of this study was to investigate the protective effects of three glycosides (rhodioside, ciwujianoside-B and astragaloside IV) on the hematopoietic system in the mice exposed to γ-rays, and to examine the possible mechanisms involved. Mice were pretreated with the glycosides (40 mg/kg, i.g.) daily for 7 days prior to radiation. The survival of mice pretreated with three glycosides after total body irradiation (6.0 Gy) was examined. Peripheral blood leucocytes and endogenous spleen colony counts, colony-forming unit-granulocyte macrophage assay, analysis of DNA content and apoptosis rate determination were performed to evaluate the effects of the three glycosides on hematogenesis. The fragmentation of double-stranded DNA in lymphocytes was detected by the comet assay. The changes in cell cycle were analysed by flow cytometry. Furthermore, the expression levels of Bcl-2, Bax and nuclear factor-kappa B (NF-κB) were measured by western blot and the electrophoretic mobility shift assay. The results showed that pretreatment with all of the glycosides improved survival time and increased the number of leucocytes, spleen colonies and granulocyte-macrophage colonies in mice exposed to 6.0 Gy γ-radiation. Rhodioside showed more protective efficacy than both ciwujianoside-B and astragaloside IV. All three glycosides significantly increased the proliferation abilities of bone marrow cells, and decreased the ratio of cells in G(0)/G(1) phase. Further analysis showed that these three glycosides were able to decrease DNA damage and the increment in the Bax/Bcl-2 ratio induced by radiation. In summary, the three glycosides showed radioprotective effects on the hematopoietic system in mice, which was associated with changes in the cell cycle, a reduction in DNA damage, and down-regulation of the ratio of Bax/Bcl-2 in bone marrow cells exposed to radiation.

Hematopoietic toxicity from lead-containing Ayurvedic medications.

BACKGROUND: Millions worldwide use Ayurvedic (traditional Indian) medicines. These medications are increasingly associated with lead poisoning, often accompanied by anemia. We compared the relative hematopoietic toxicity of Ayurvedic lead poisoning with a common form of occupational lead poisoning. MATERIAL/METHODS: We retrospectively studied 66 adult lead intoxications: 43 published Ayurvedic cases identified in published reports by searching MEDLINE (1966 to November 2005); 4 Ayurvedic patients seen at a referral center; and 19 lead paint intoxications from the same center. We considered patients' age, gender and blood lead at presentation, and then compared the groups with respect to hematopoietic parameters. RESULTS: Ayurvedic lead poisoning was associated with higher blood lead (p<0.001), more basophilic stippling (p<0.001), lower hemoglobin (p<0.001) and higher protoporphyrin (p<0.001). Multiple regression adjusted for blood lead and gender found Ayurvedic lead poisoning associated with a 36.2 g/L (95% CI -48.8, -23.6 g/L) greater decrement in hemoglobin (p<0.001) as compared to paint-removal poisoning. CONCLUSIONS: Ayurvedic poisoning produces greater hematopoietic toxicity than paint-removal poisoning. Ayurvedic ingestion should be considered in patients with anemia. Ayurveda users should be screened for lead exposure and strongly encouraged to discontinue metal-containing remedies.

Prophylactic dose of neem (Azadirachta indica) leaf preparation restricting murine tumor growth is nontoxic, hematostimulatory and immunostimulatory.

Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hundred percent of mice could tolerate 4 injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight ratios and physical behavior of treated mice remained completely unchanged during treatment with different NLP doses. All of these NLP doses were observed to stimulate hematological systems as evidenced by the increase in total count of RBC, WBC and platelets and hemoglobin percentage. As histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP was proved. The level of serum urea remained unaltered and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment. Increased antibody production against B16 melanoma antigen was detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units could not exhibit such immunostimulatory changes; NLP mediated immunostimulation was correlated well with the growth restriction of murine carcinoma. In other words, tumor growth restriction was observed only when mice were injected with immunostimulatory doses of NLP (0.5 unit and 1 unit).

Oral oxymetholone reduces mortality induced by gamma irradiation in mice through stimulation of hematopoietic cells.

Oxymetholone is a 17alpha -alkylated anabolic-androgenic steroid. This drug can stimulate bone marrow cells and increase the blood cells in the peripheral blood vessels. It has been used for the treatment of anemia caused by low red cell production. Since oxymetholone has hematopoietic effect, we studied radioprotective effects of this drug in mice. In this study, we determined percentage of survival, dose-reduction factor (DRF) and hematological parameters in irradiated mice which treated with or without oxymetholone. Oxymetholone administrated at different doses 80, 160, 320, 640 mg/kg by gavages at 24 h before 8 Gy gamma irradiation. At 30 days after treatment, the following percentage of animals survival in each group was as: 80 mg/kg, 50%; 160 mg/kg, 50%; 320 mg/kg, 55%; 640 mg/kg, 75% and vehicle, 15%. Percentage of survival increased in all of treated groups statistically compared with irradiated-vehicle group. In the groups treated by oxymetholone, maximum protection was realized at 640 mg/kg. In order to calculate the DRF for oxymetholone, mice were exposed to whole-body gamma irradiation with dose ranges between 5.83 and 11.23 Gy. The probit line for oxymetholone-treated mice was shifted to the right with a DRF of 1.14. In mice exposed to whole-body gamma-irradiation (4 Gy), an oral administration of 640 mg/kg oxymetholone ameliorated radiation-induced decreases in circulating platelets and erythrocytes, but had a less effect on total number of WBC. These results demonstrate that oxymetholone stimulates myelopoiesis and thrombocytopenia and enhances survival in mice after ionizing radiation.

Soy isoflavone aglycone modulates a hematopoietic response in combination with soluble beta-glucan: SCG.

Soy isoflavone aglycones (IFAs) have a wide range of biological actions that suggest they may be of use in cancer prevention. On the other hand, a branched beta-glucan from Sparassis crispa (SCG) is a major 6-branched 1,3-beta-D-glucan in an edible/medicinal mushroom: Sparassis crispa showing antitumor activity. We have previously reported that both oral and intraperitoneal administration of SCG enhanced the hematopoietic response in cyclophosphamide (CY)-induced leukopenic mice. In this study, we investigated the hematopoietic response due to IFA in combination with SCG in CY-induced leukopenic mice. The oral administration of IFA in combination with SCG synergistically enhanced the number of white blood cells, and increased spleen weight. Analyzing the leukocyte population by flow cytometry, the combination of IFA and SCG increased the number of monocytes and granulocytes in the spleen. Taken together, the combination of IFA and SCG synergistically provides the hematopoietic responses that are enhanced over IFA or SCG alone.

[The influence of Bazhen decoction on hematopoietic modulator in anaemic mice].

This study was designed to evaluate the effect of Bazhen decoction on bone marrow depression induced by cyclophosphamide (CY) in mice. An experimental model of mouse bone marrow injury was established through cyclophosphamide induced and the following phenomena were observed. The techniques of culture of hematopoietic progenitor cell and hematopoietic growth factor assay were used. Bazhen decoction could obviously promote the proliferation of bone marrow cells of anaemic mice. The culture media of spleen cell, macrophage, lung and skeletal muscle treated with Bazhen decoction had much stronger stimulating effects on hematopoietic cells. The bone marrow cells of the anaemic mice could yield TNF through Bazhen decoction treatment. It was suggested that Bazhen decoction is clinically a hopeful drug used to cure bone marrow depression and attenuate the side effects of CY.

Radiation protective effect of an extract from Chelidonium majus.

We earlier reported that CM-AIa isolated from Chelidonium majus had mitogenic activity, generated lymphokine-activated killer cells, and increased the number of granulocyte-macrophage colony-forming cells (GM-CFC). In an extended effort to search for other immunostimulatory effects, we evaluated the protective effects of in vivo injected CM-AIa against irradiation. CM-AIa was found to increase the number of bone marrow cells, spleen cells, GM-CFC, and platelets in irradiated mice. In addition, this agent induced endogenous production of cytokines such as interleukin 1 and tumor necrosis factor alpha, which are required for hematopoietic recovery. We also demonstrated that CM-AIa treatment 24 hours before irradiation protected mice with 80% survival at lethal dose 100/15. These findings indicate that CM-AIa may be a useful agent for reducing the time needed for reconstitution of hematopoietic cells after irradiation treatment.

Hyperbaric oxygen enhances apoptosis in hematopoietic cells.

Hyperbaric oxygen (HBO) is 100% oxygen administered at elevated atmospheric pressure. In this study, we examined the effect of HBO on hematopoietic cell apoptosis. Cells exposed to HBO were incubated in a chamber containing 97.9% O(2) and 2.1% CO(2) at 2.4 atmospheres absolute (ATA). HBO enhanced spontaneous HL-60 cell apoptosis in a time-dependent manner; a 12 h exposure increased apoptosis by 42%. Exposing these cells to hyperoxia at standard atmospheric pressure (95% O(2), 5% CO(2) at 1 ATA) or increased pressure alone (8.75% O(2), 2.1% CO(2) at 2.4 ATA) had minimal effect on apoptosis. HBO also enhanced stimulus-induced apoptosis. HL-60 cells stimulated to die using gamma radiation underwent 33% more apoptosis than cells exposed to radiation alone. HBO enhanced melphalan, camptothecin, and chlorambucil-induced apoptosis by 22%, 13%, and 8%, respectively. Jurkat cells stimulated to die with anti-Fas antibody underwent 44% more apoptosis when exposed to HBO. Spontaneous apoptosis was increased by 15% in HBO-exposed murine thymocytes. HBO's effect on apoptosis did not require new protein synthesis. As expected, HBO exposure increased the intracellular concentration of H(2)O(2). Incubating HL-60 cells in the presence of dehydroascorbic acid partially abrogated HBO-induced increases in intracellular H(2)O(2) and apoptosis. In summary, HBO enhances spontaneous and stimulus-induced apoptosis in hematopoietic cells, at least in part, by enhancing the intracellular accumulation of H(2)O(2).

Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs.

OBJECTIVE: To evaluate the effects of arsenic (III) exposure on porphyrin metabolism and the central nervous system supplemented with data on the effect of hepatic and renal tissues of rats and guinea pigs. METHODS: Rats and guinea pigs were exposed to 10 or 25 ppm arsenic in drinking water for 16 weeks. RESULTS: Following chronic arsenic (III) exposure, delta-aminolevulinic acid dehydratase activity in blood showed a significant reduction as did the total cell counts (RBC and WBC) and reduced glutathione with increased urinary delta-aminolevulinic acid. Zinc protoporphyrin, a sensitive indicator of iron deficiency and impairment of heme biosynthesis, showed a significant increase in arsenic exposure. The hepatic delta-aminolevulinic acid dehydratase and delta-aminolevulinic acid synthetase activity increased in chronic arsenic (III) exposure in rats and guinea pigs. Significant changes in the steady-state level of three major neurotransmitters, dopamine, norepinephrine, and 5-hydroxytryptamine, and monoamine oxidase were observed following chronic arsenic (III) exposure. CONCLUSION: At low doses (10 and 25 ppm in drinking water), the effects of arsenic on hematopoietic indices and whole-brain neurotransmitter concentrations were more prominent in guinea pigs than in rats with some variability in the dose response.