Associations of morning urinary 1-bromopropane metabolite with peripheral blood parameters in a community-based population / 环境与职业医学

Background As an environmental pollutant, 1-bromopropane (1-BP) is ubiquitous in the living environment. However, its health effects on the general population are still unclear. Objective To assess the associations between urinary 1-BP metabolite and blood routine indices in a Chinese community population. Methods A total of 3512 community residents aged 18-80 years from the baseline of the Wuhan-Zhuhai cohort were included in our study. The demographic characteristics, disease history, and lifestyles of the participants were collected through questionnaires. Height, weight, blood pressure, and other anthropometrics were collected through physical examination. Blood routine indicators were tested using an automated hematology analyzer. Urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-L-cysteine (BPMA) was measured by ultra-high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Generalized linear models and logistic regression models were used to assess the associations of urinary BPMA with blood routine indices and the risks of abnormal blood routine indices, respectively. Besides, stratified analysis and effect modification analysis were further conducted to investigate the effects of individual characteristics and lifestyles on the associations of urinary BPMA with blood routine indices. All models were adjusted for gender, age, and other potential confounders. Results The mean age of the study population (30.1% male) was (52.78±12.77) years. The median (P25, P75) level of urinary BPMA adjusted for urinary creatinine was 0.90 (0.50, 1.73) mg·mol−1. In the analysis with target indicator as continuous variable, each 1-unit increase in natural logarithm-transformed urinary BMPA level was associated with a 0.078×109 L−1, 0.031×109 L−1, 0.307%, 3.518 g·L−1, and 2.469×109 L−1 decrease in white blood cell, lymphocyte, lymphocyte percentage, mean corpuscular hemoglobin concentration, and platelet levels, respectively (all Ps<0.05); and with a 0.440%, 1.140 fL, 0.014 fL, and 0.020 increase in hematocrit, mean corpuscular volume, and natural logarithm-transformed levels of mean platelet volume and mean platelet volume/platelet, respectively (all Ps<0.05). The categorical analysis across quartiles of BPMA level showed that BPMA was inversely associated with lymphocyte percentage, mean corpuscular hemoglobin concentration, and platelet levels in a dose-dependent manner (all Ptrend<0.05), and positively related to hematocrit, mean corpuscular volume, mean platelet volume, and mean platelet volume/platelet levels in a dose-dependent manner (all Ptrend<0.05). Body mass index, smoking, and drinking modified the associations of urinary BPMA level with red blood cell, mean corpuscular hemoglobin concentration lymphocyte percentage, and hemoglobin (all Ps<0.05). In addition, urinary BPMA was associated with an increased risk of abnormal increase in mean corpuscular volume (OR=1.316, 95%CI: 1.171-1.478) and red blood cell volume distribution width (OR=1.255, 95%CI: 1.030-1.528), and abnormal decrease in mean corpuscular hemoglobin concentration (OR=1.200, 95%CI: 1.035-1.392). Conclusion Exposure to 1-BP of the general population is associated with decreased white blood cells and platelets, as well as abnormal change of blood cell morphology or function.

Mechanism of Huangqintang in Alleviating Side Effect of Chemotherapy for Endometrial Cancer Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo evaluate the utility and mechanism of Huangqintang combined with carboplatin in chemotherapy of endometrial cancer by experiments as well as network pharmacology and molecular docking. MethodThe xenograft model of endometrial carcinoma was induced in BALB/c nude mice. When the tumor volume reached about 100 mm3，24 nude mice were randomly assigned into a model group， a Huangqintang group （3.5 g·kg-1），a carboplatin group （50 mg·kg-1），and a combination group （3.5 g·kg-1 Huangqintang + 50 mg·kg-1 carboplatin）， with six mice in each group. The mice in the model group received 200 μL of normal saline by gavage， twice a day. The volume of the tumor and the body weight of the mice were measured every two days. After drug intervention for 20 days， the blood of the mice was collected for renal function and blood routine tests. Then the nude mice were euthanized and the tumor was weighted. In combination with the experimental results，the underlying mechanism of Huangqintang combined carboplatin was predicted through network pharmacology and the binding sites of active components were predicted by molecular docking. ResultThe tumor inhibition rates of the Huangqintang group，the carboplatin group， and the combination group were 8.87%，50.33% （P<0.05），and 64.66% （P<0.01），respectively. Compared with the results in the model group，the body weight，leukocyte，erythrocyte， and hemoglobin in the carboplatin group decreased，and creatinine and uric acid increased （P<0.05）. Compared with the carboplatin group，the combination group showed increased body weight，leukocyte， and hemoglobin （P<0.05），and decreased creatinine and uric acid （P<0.05）. A total of 114 potential active components of Huangqintang involved 200 targets related to the side effects of carboplatin. The core genes involved were mainly heat shock protein 90AA1 （HSP90AA1），transcription factor c-Jun （JUN）， and mitogen-activated protein kinase （MAPK）. Molecular docking showed that baicalein and wogonin could form a stable protein complex with HSP90AA1， serving as potential active molecules. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis revealed that it might be related to the regulation of tumor necrosis factor（TNF） signaling pathway，interleukin（IL）-17 signaling pathway， MAPK signaling pathway， and toll-like receptor pathway. ConclusionHuangqintang has no obvious inhibitory effect on endometrial cancer，and the tumor suppression effect is not significantly enhanced after combination with carboplatin，but Huangqintang can alleviate carboplatin-induced side effects. The mechanism may be related to the complex network of Chinese medicine.

Neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane in male offspring rats / 中国职业医学

OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.

Occupational exposure to pesticides and hematological alterations: A survey of farm residents in the South of Brazil / Exposição ocupacional a agrotóxicos e alterações hematológicas: Estudo transversal em moradores rurais do Sul do Brasil

Abstract This study sought to investigate the association of exposure to organochlorine (OC) and non-persistent pesticides with hematological parameters in an agricultural population in Southern Brazil. A cross-sectional study was conducted with a random sample of 275 farm workers and their families in Farroupilha-RS. A questionnaire was used to collect information on sociodemographic and lifestyle factors, duration, frequency and type of pesticide used, among others. Blood samples were collected and analyzed for serum concentration of 24 OC pesticides and hematological parameters. Associations were explored through linear regression, controlling for confounders. Lifetime use of chemical classes other than organophosphates and dithiocarbamates were associated with decreased number of lymphocytes, while subjects sampled in the high pesticide use season showed higher number of erythrocytes and hemoglobin level. Detectable serum levels of many OC pesticides were associated with lower counts of white blood cells, particularly eosinophils. Although mostly null associations were observed between pesticide use and hematological parameters, findings may suggest that OC pesticides could lead to hematological alterations among agricultural workers.

Resumo O objetivo deste estudo foi investigar a associação entre a exposição a organoclorados (OC) e agrotóxicos não persistentes e os parâmetros hematológicos em uma população agrícola de Farroupilha-RS. Foi utilizado um questionário para coletar informações sobre fatores sociodemográficos e de estilo de vida, duração, frequência e tipo de pesticidas utilizados, entre outros. Amostras sanguíneas foram coletadas e analisadas quanto a concentração sérica de 24 pesticidas OC e parâmetros hematológicos. As associações foram exploradas através de regressão linear, controlando por confundidores. O uso cumulativo de classes químicas diferentes de organofosforados e ditiocarbamatos associou-se com diminuição do número de linfócitos enquanto indivíduos que tiveram suas coletas sanguíneas realizadas na estação de maior uso de agrotóxicos tinham contagem de eritrócitos e hemoglobina maiores. Níveis séricos de diversos pesticidas organoclorados foram associados com contagens mais baixas de células brancas do sangue, particularmente eosinófilos. Embora as associações com o uso de agrotóxicos tenham sido, em geral, nulas, os resultados podem sugerir que os pesticidas OCs poderiam levar a alterações hematológicas entre os trabalhadores agrícolas.

Chlorambucil and ascorbic acid-mediated anticancer activity and hematological toxicity in Dalton's ascites lymphoma-bearing mice.

Chlorambucil is an anticancer drug with alkylating and immunosuppressive activities. Considering various reports on the possible antioxidant/protective functions of ascorbic acid (vitamin C), it was aimed at to explore the modulatory effect of ascorbic acid on therapeutic efficacy and toxicity induced by chlorambucil. Dalton’s ascites lymphoma tumor serially maintained in Swiss albino mice were used for the present experiments. The result of antitumor activity showed that combination treatment with ascorbic acid and chlorambucil exhibited enhanced antitumor activity with 170% increase in life span (ILS), which is significantly higher as compared to chlorambucil alone (ILS 140%). Analysis of apoptosis in Dalton’s lymphoma tumor cells revealed a significantly higher apoptotic index after combination treatment as compared to chlorambucil alone. Blood hemoglobin content, erythrocytes and leukocytes counts were decreased after chlorambucil treatment, however, overall recovery in these hematological values was noted after combination treatment. Chlorambucil treatment also caused morphological abnormalities in red blood cells, majority of which include acanthocytes, burr and microcystis. Combination treatment of mice with ascorbic acid plus chlorambucil showed less histopathological changes in kidney as compared to chlorambucil treatment alone, thus, ascorbic acid is effective in reducing chlorambucil-induced renal toxicity in the hosts. Based on the results, for further devel­opment, hopefully into the clinical usage, the administration of ascorbic acid in combination with chlorambucil may be recommended.

Seguridad hepática y hemática de la amodiaquina en el tratamiento de la malaria no complicada por plasmodium falciparum / Liver and haematological safety of amodiaquine treatment in non-complicated falciparum malaria

Introducción: Actualmente existe un número limitado de antimaláricos eficaces, entre ellos amodiaquina; sin embargo, su uso se ha restringido por informes previos de toxicidad hepática y hemática a dosis superiores a 1,500 mg administradas como profiláctico para malaria. No obstante, en dosis terapéuticas antimaláricas los efectos adversos son de intensidad leve o moderada, e incluyen náuseas, vómito y prurito. Objetivo: Evaluar la toxicidad hepática y hemática de la amodiaquina en dosis y tiempo establecidos para tratar la malaria por Plasmodium falciparum no complicada. Metodología: Diseño longitudinal con determinación no ciega del efecto. Se captaron 57 pacientes, seguidos por 10 días (evaluación clínico-parasitológica). Resultados: Antes del tratamiento, las variables hemáticas y hepáticas mostraron alteración leve y se normalizaron postratamiento, que fue 100% eficaz. Los días 5 y 10 del tratamiento todas las variables estaban normales, lo que sugiere ausencia de efectos tóxicos imputables al medicamento. Los efectos adversos fueron pocos, leves y desaparecieron completamente el día 10. Conclusiones: Usada en la dosis (25 mg/kg peso) y el tiempo (3 días) definidos para el tratamiento de la malaria por P. falciparum sin complicaciones, la amodiaquina no mostró efectos adversos ni toxicidad hepática ni hemática.

Background: At present there are few effective antimalarial drugs, amodiaquine is one of them; however, its use has been restricted by previous information about hematic and hepatic toxicity when it is administered as prophylactic at doses greater than 1,500 mg. But at therapeutic doses, the side effects are either slight or of moderate intensity and include nausea, vomit and pruritus. Objective: To evaluate the hepatic and hematic toxicity of amodiaquine administered at doses and time recommended for treatment of uncomplicated Plasmodium falciparum malaria. Methods: Longitudinal design with no blind determination of the effect. A total of 57 patients were included and followed up for 10 days (clinical-parasitological evaluation). Results: Hematic and hepatic variables showed slight alteration previous treatment and were normal postreatment. Therapeutic efficacy of amodiaquine was 100%. All variables were normal at days 5 and 10, suggesting absence of toxic effects imputable to amodiaquine. The side effects were few, slight and disappeared completely at day 10. Conclusions: Amodiaquine administered at doses (25 mg/kg weight) and time (3 days) established for treatment of uncomplicated Plasmodium falciparum malaria is safe, it did not show neither hematic nor hepatic toxicity.

Systemic and myelotoxic effects of single administration of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats

<p><b>OBJECTIVE</b>Systemic and myelotoxic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) were examined by the single administration of TBDD by gavage to rats.</p><p><b>METHODS</b>Fifteen Wistar rats of both sexes per group received 0, 10, 30, 100 or 300 μg TBDD/kg body weight. Rats surviving to the scheduled necropsy on Days 2, 7 and 36 after TBDD administration were examined for growth rate, organ weight, hematology, histopathology and adipose tissue levels of TBDD.</p><p><b>RESULTS</b>Three 300 μg/kg-dosed females died on Days 21, 23 and 27, and exhibited a marked decrease in body weight, severe thymic atrophy, decreased bone marrow hematopoiesis and hemorrhage in the subarachnoid space of brain and spinal cord. TBDD-dosed surviving rats exhibited growth retardation, decreased bone marrow hematopoiesis, decreases in red blood cell counts, hemoglobin concentrations, and hematocrit values, an increase in reticulocytes and decreases in platelet counts, white blood cell counts and eosinophils. These signs suggested TBDD myelotoxicity. Splenic extramedullary hematopoiesis was increased in both sexes given TBDD, whereas atrophy of the splenic white pulp occurred only in TBDD-dosed females. Marked decreases in body weights and the size and weight of the thymus, severe thymic atrophy and death in TBDD-dosed females suggested a wasting syndrome. The adipose tissue level of TBDD culminated on Day 7 and decreased to 20-30% of the Day 7 level on Day 36.</p><p><b>CONCLUSIONS</b>The TBDD-induced effects were characterized by a wasting syndrome and myelotoxicity that appeared at the dose levels of 30 μg/kg and higher and caused death in 300 μg/kg-dosed females.</p>

Systemic and Myelotoxic Effects of Single Administration of 2,3,7,8-Tetrabromodibenzo-\it{p}-Dioxin in Rats

Objective: Systemic and myelotoxic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) were examined by the single administration of TBDD by gavage to rats. Methods: Fifteen Wistar rats of both sexes per group received 0, 10, 30, 100 or 300 μg TBDD/kg body weight. Rats surviving to the scheduled necropsy on Days 2, 7 and 36 after TBDD administration were examined for growth rate, organ weight, hematology, histopathology and adipose tissue levels of TBDD. Results: Three 300 μg/kg-dosed females died on Days 21, 23 and 27, and exhibited a marked decrease in body weight, severe thymic atrophy, decreased bone marrow hematopoiesis and hemorrhage in the subarachnoid space of brain and spinal cord. TBDD-dosed surviving rats exhibited growth retardation, decreased bone marrow hematopoiesis, decreases in red blood cell counts, hemoglobin concentrations, and hematocrit values, an increase in reticulocytes and decreases in platelet counts, white blood cell counts and eosinophils. These signs suggested TBDD myelotoxicity. Splenic extramedullary hematopoiesis was increased in both sexes given TBDD, whereas atrophy of the splenic white pulp occurred only in TBDD-dosed females. Marked decreases in body weights and the size and weight of the thymus, severe thymic atrophy and death in TBDD-dosed females suggested a wasting syndrome. The adipose tissue level of TBDD culminated on Day 7 and decreased to 20–30% of the Day 7 level on Day 36. Conclusions: The TBDD-induced effects were characterized by a wasting syndrome and myelotoxicity that appeared at the dose levels of 30 μg/kg and higher and caused death in 300 μg/kg-dosed females.

Inhibitive and toxic effects of artesunate on murine bone marrow hematopoietic stem and progenitor cells / 中国临床药理学与治疗学

AIM:To observe the influences of artesunate(AS)on murine bone marrow hematopoietic stem and progenitor cells.METHODS:Murine bone marrow hematopoietic stem and progenitor cells were cultured in vitro with different concentration of AS.The numbers of erythrocyte colony-forming unit(CFU-E)or burst-forming unit(BFU-E)in liquid or semisolid culture were counted through light microscope.Apoptosis of cultured cells and the changes of mitochondrial membrane potential were detected by flow cytometry(FCM)analysis,meanwhile,DNA ladder gel electrophoresis were conducted.RESULTS:AS could significantly inhibit the formation of CFU-E and BFU-E(P