RESUMO
AIM: To investigate the effects of ginsenoside Rg1 on the radiation-induced aging of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying mechanisms. METHODS: Male C57BL/6 mice were treated with ginsenoside Rg1 (20 mg·kg(-1)·d(-1), ip) or normal saline (NS) for 7 d, followed by exposure to 6.5 Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but without irradiation. Sca-1(+) HSC/HPCs were isolated and purified from their bone marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative activities, senescence-related markers senescence-associated ß-galactosidase (SA-ß-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d 7. RESULTS: The irradiation caused dramatic reduction in the number of Sca-1(+) HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham-irradiated group. The irradiation significantly decreased SOD activity, increased MDA contents and caused DNA damage in Sca-1(+) HSC/HPCs. Moreover, the irradiation significantly increased SA-ß-gal staining, reduced CFU-mix forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1(+) HSC/HPCs. Administration of ginsenoside Rg1 caused small, but significant recovery in the number of Sca-1(+) HSC/HPCs on d 3 and d 7. Furthermore, ginsenoside Rg1 significantly attenuated all the irradiation-induced changes in Sca-1(+) HSC/HPCs, including oxidative stress reaction, DNA damage, senescence-related markers and cellular senescence signaling pathways and cell cycle, etc. CONCLUSION: Administration of ginsenoside Rg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle.
Assuntos
Senescência Celular/efeitos da radiação , Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacologia , Células-Tronco Hematopoéticas/efeitos da radiação , Irradiação Corporal Total/efeitos adversos , Animais , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição AleatóriaRESUMO
BACKGROUND: Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs), lead, and mercury are released by combustion of coal and other fossil fuels. OBJECTIVES: In the present study we evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age. METHODS: The study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air. In a cohort of nonsmoking women and their newborns enrolled between March 2002 and June 2002, we measured levels of PAH-DNA adducts, lead, and mercury in umbilical cord blood. PAH-DNA adducts (specifically benzo[a]pyrene adducts) provided a biologically relevant measure of PAH exposure. We also obtained developmental quotients (DQs) in motor, adaptive, language, and social areas. RESULTS: Decrements in one or more DQs were significantly associated with cord blood levels of PAH-DNA adducts and lead, but not mercury. Increased adduct levels were associated with decreased motor area DQ (p = 0.043), language area DQ (p = 0.059), and average DQ (p = 0.047) after adjusting for cord lead level, environmental tobacco smoke, sex, gestational age, and maternal education. In the same model, high cord blood lead level was significantly associated with decreased social area DQ (p = 0.009) and average DQ (p = 0.038). CONCLUSION: The findings indicate that exposure to pollutants from the power plant adversely affected the development of children living in Tongliang; these findings have implications for environmental health policy.
Assuntos
Poluentes Atmosféricos/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Carvão Mineral/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Desenvolvimento Infantil/fisiologia , Pré-Escolar , China , Feminino , Humanos , Entrevistas como Assunto , Chumbo/toxicidade , Masculino , Mercúrio/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Centrais Elétricas , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologiaRESUMO
BACKGROUND: Coal burning provides 70% of the energy for China's industry and power, but releases large quantities of polycyclic aromatic hydrocarbons (PAHs) and other pollutants. PAHs are reproductive and developmental toxicants, mutagens, and carcinogens. OBJECTIVE: We evaluated the benefit to neurobehavioral development from the closure of a coal-fired power plant that was the major local source of ambient PAHs. METHODS: The research was conducted in Tongliang, Chongqing, China, where a coal-fired power plant operated seasonally before it was shut down in May 2004. Two identical prospective cohort studies enrolled nonsmoking women and their newborns in 2002 (before shutdown) and 2005 (after shutdown). Prenatal PAH exposure was measured by PAH-DNA adducts (benzo[a]pyrene-DNA) in umbilical cord blood. Child development was assessed by the Gesell Developmental Schedules at 2 years of age. Prenatal exposure to other neurotoxicants and potential confounders (including lead, mercury, and environmental tobacco smoke) was measured. We compared the cohorts regarding the association between PAH-DNA adduct levels and neurodevelopmental outcomes. RESULTS: Significant associations previously seen in 2002 between elevated adducts and decreased motor area developmental quotient (DQ) (p = 0.043) and average DQ (p = 0.047) were not observed in the 2005 cohort (p = 0.546 and p = 0.146). However, the direction of the relationship did not change. CONCLUSION: The findings indicate that neurobehavioral development in Tongliang children benefited by elimination of PAH exposure from the coal-burning plant, consistent with the significant reduction in PAH-DNA adducts in cord blood of children in the 2005 cohort. The results have implications for children's environmental health in China and elsewhere.
Assuntos
Poluentes Atmosféricos/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Carvão Mineral , Sistema Nervoso/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Pré-Escolar , Exposição Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Sistema Nervoso/crescimento & desenvolvimento , Compostos Policíclicos/toxicidade , Gravidez , Inquéritos e QuestionáriosRESUMO
Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic pollutants released by fossil fuel combustion. Other pollutants include metals and particulate matter. PAH-DNA adducts, or benzo[a]pyrene (BaP) adducts as their proxy, provide a chemical-specific measure of individual biologically effective doses that have been associated with increased risk of cancer and adverse birth outcomes. In the present study we examined the relationship between prenatal PAH exposure and fetal and child growth and development in Tongliang, China, where a seasonally operated coal-fired power plant was the major pollution source. In a cohort of 150 nonsmoking women and their newborns enrolled between 4 March 2002 and 19 June 2002, BaP-DNA adducts were measured in maternal and umbilical cord blood obtained at delivery. The number of gestational months occurring during the period of power plant operation provided a second, more general measure of exposure to plant emissions, in terms of duration. High PAH-DNA adduct levels (above the median of detectable adduct level) were associated with decreased birth head circumference (p=0.057) and reduced children's weight at 18 months, 24 months, and 30 months of age (p<0.05), after controlling for potential confounders. In addition, in separate models, longer duration of prenatal exposure was associated with reduced birth length (p=0.033) and reduced children's height at 18 (p=0.001), 24 (p<0.001), and 30 months of age (p<0.001). The findings suggest that exposure to elevated levels of PAHs, with the Tongliang power plant being a significant source, is associated with reduced fetal and child growth in this population.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Adutos de DNA/sangue , Poluentes Ambientais/sangue , Sangue Fetal/química , Desenvolvimento Fetal/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/sangue , Adulto , Peso ao Nascer , Coleta de Amostras Sanguíneas , Estatura , Pré-Escolar , China/epidemiologia , Carvão Mineral , Adutos de DNA/efeitos adversos , Interpretação Estatística de Dados , Poluentes Ambientais/efeitos adversos , Feminino , Crescimento/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Centrais Elétricas , Gravidez , Resultado da Gravidez , Caracteres Sexuais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To study the clinical values of positron emission tomography (PET) in preterm and term newborn infants through observing brain glucose metabolism by (18)F-fluorodeoxyglucose ((18)F-FDG) PET. METHOD: To observe the brain (18)F-FDG PET imaging in 9 term and 7 preterm newborn infants in the same condition after administration of 0.1 mCi/kg (18)F-FDG. RESULT: The brain (18)F-FDG PET imaging showed that the uptake of (18)F-FDG was relatively more in the thalamus, and less in the cerebral cortex in preterm and term newborn infants. The uptake of (18)F-FDG of cerebral cortex in preterm infants was less than that in term infants, so the structure of brain (18)F-FDG PET imaging was a little fainter in preterm neonates as compared with that in term newborns. CONCLUSION: (18)F-FDG PET imaging could show different glucose metabolisms of brain in preterm and term infants. Brain (18)F-FDG PET imaging might be a useful tool for estimating the brain function in newborn infants, and its clinical values need further investigation.