Marjo Niittynen

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXα reductase and δ-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin and its monoglucuronide in moderately TCDD-resistant line B rats, but not in highly TCDD-resistant line A rats. In the mammalian heme degradation process, heme is cleaved to biliverdin by the rate-limiting enzyme heme oxygenase-1 (HO-1). Subsequently, biliverdin IXalpha reductase (BVRA) catalyzes the reduction of biliverdin to bilirubin. In heme biosynthesis, the rate-limiting enzyme is delta-aminolevulinic acid synthetase 1 (ALAS1). The effect of TCDD on HO-1, BVRA and ALAS1 was studied at the levels of mRNA (all three enzymes), protein expression (HO-1), and enzymatic activity (BVRA, liver only) in order to determine whether the accumulation of biliverdin could be due to their altered expression. In both lines A and B, 300 microg/kg TCDD transiently repressed hepatic HO-1 mRNA on day 2 but induced HO-1 protein expression at later time-points; however, the impact emerged earlier (day 14 vs. day 35) in line B rats. In spleen, TCDD repressed HO-1 mRNA and protein expression in lines A and B through days 2-35, but did not affect its mRNA levels in TCDD-sensitive L-E rats (10 days after 100 microg/kg). In all rat strains/lines, there was a strong repression of ALAS1 and a moderate induction of BVRA mRNA in liver, but mostly not in spleen. Hepatic BVRA activity was increased in lines A and B on day 14. At 5 weeks, it was still elevated in line A but reduced to 51% of control in line B. The results suggest that hepatic heme degradation is induced by TCDD in rats; however, this does not alone explain the accumulation of biliverdin in line B rats. Other factors such as the late repression of BVRA found here and possibly oxidative stress may be important contributors to biliverdin accumulation in these rats.

Immediate and highly sensitive aversion response to a novel food item linked to AH receptor stimulation

Aversion to novel food items was studied in male rats and mice after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure using chocolate consumption as an indicator. The correlation of this phenomenon with susceptibility to acute toxicity and CYP1A1 induction was examined by determining the dose-response of chocolate aversion in differently dioxin-sensitive rat lines after TCDD (0.01-10 μg/kg). Furthermore, the dependence of this behavioral alteration on the AH receptor (AHR) was studied employing AHR-deficient and wild-type mice. We offered chocolate for both species as a novel food item immediately after the exposure, and it was available with standard rodent chow for 3 days. The ED₅₀ value for the extremely resistant rat line A (LD₅₀) value > 10,000 μg/kg) was 0.36 μg/kg, for the semi-resistant line B (LD₅₀) value 830 μg/kg) 1.07 μg/kg and for the TCDD-sensitive line C (LD₅₀ value 40 μg/kg) 0.34 μg/kg. Interestingly, the ED₅₀ values for chocolate aversion were very similar to those for CYP1A1 induction in these rat lines. Findings on AHR-deficient and wild-type mice implied the involvement of the AHR in this intriguing response, which may thus represent a mechanism to restrict exposure to potentially toxic dietary substances causing hepatic induction of drug-metabolizing enzymes.

Building-related health impacts in European and Chinese cities: a scalable assessment method

BackgroundPublic health is often affected by societal decisions that are not primarily about health. Climate change mitigation requires intensive actions to minimise greenhouse gas emissions in the future. Many of these actions take place in cities due to their traffic, buildings, and energy consumption. Active climate mitigation policies will also, aside of their long term global impacts, have short term local impacts, both positive and negative, on public health.Our main objective was to develop a generic open impact model to estimate health impacts of emissions due to heat and power consumption of buildings. In addition, the model should be usable for policy comparisons by non-health experts on city level with city-specific data, it should give guidance on the particular climate mitigation questions but at the same time increase understanding on the related health impacts and the model should follow the building stock in time, make comparisons between scenarios, propagate uncertainties, and scale to different levels of detail.We tested The functionalities of the model in two case cities, namely Kuopio and Basel. We estimated the health and climate impacts of two actual policies planned or implemented in the cities. The assessed policies were replacement of peat with wood chips in co-generation of district heat and power, and improved energy efficiency of buildings achieved by renovations.ResultsHealth impacts were not large in the two cities, but also clear differences in implementation and predictability between the two tested policies were seen. Renovation policies can improve the energy efficiency of buildings and reduce greenhouse gas emissions significantly, but this requires systematic policy sustained for decades. In contrast, fuel changes in large district heating facilities may have rapid and large impacts on emissions. However, the life cycle impacts of different fuels is somewhat an open question.ConclusionsIn conclusion, we were able to develop a practical model for city-level assessments promoting evidence-based policy in general and health aspects in particular. Although all data and code is freely available, implementation of the current model version in a new city requires some modelling skills.

Public health impacts of city policies to reduce climate change: findings from the URGENCHE EU-China project

BackgroundClimate change is a global threat to health and wellbeing. Here we provide findings of an international research project investigating the health and wellbeing impacts of policies to reduce greenhouse gas emissions in urban environments.MethodsFive European and two Chinese city authorities and partner academic organisations formed the project consortium. The methodology involved modelling the impact of adopted urban climate-change mitigation transport, buildings and energy policy scenarios, usually for the year 2020 and comparing them with business as usual (BAU) scenarios (where policies had not been adopted). Carbon dioxide emissions, health impacting exposures (air pollution, noise and physical activity), health (cardiovascular, respiratory, cancer and leukaemia) and wellbeing (including noise related wellbeing, overall wellbeing, economic wellbeing and inequalities) were modelled. The scenarios were developed from corresponding known levels in 2010 and pre-existing exposure response functions. Additionally there were literature reviews, three longitudinal observational studies and two cross sectional surveys.ResultsThere are four key findings. Firstly introduction of electric cars may confer some small health benefits but it would be unwise for a city to invest in electric vehicles unless their power generation fuel mix generates fewer emissions than petrol and diesel. Second, adopting policies to reduce private car use may have benefits for carbon dioxide reduction and positive health impacts through reduced noise and increased physical activity. Third, the benefits of carbon dioxide reduction from increasing housing efficiency are likely to be minor and co-benefits for health and wellbeing are dependent on good air exchange. Fourthly, although heating dwellings by in-home biomass burning may reduce carbon dioxide emissions, consequences for health and wellbeing were negative with the technology in use in the cities studied.ConclusionsThe climate-change reduction policies reduced CO2 emissions (the most common greenhouse gas) from cities but impact on global emissions of CO2 would be more limited due to some displacement of emissions. The health and wellbeing impacts varied and were often limited reflecting existing relatively high quality of life and environmental standards in most of the participating cities; the greatest potential for future health benefit occurs in less developed or developing countries.

Public health impacts of city policies to reduce climate change

BackgroundClimate change is a global threat to health and wellbeing. Here we provide findings of an international research project investigating the health and wellbeing impacts of policies to reduce greenhouse gas emissions in urban environments.MethodsFive European and two Chinese city authorities and partner academic organisations formed the project consortium. The methodology involved modelling the impact of adopted urban climate-change mitigation transport, buildings and energy policy scenarios, usually for the year 2020 and comparing them with business as usual (BAU) scenarios (where policies had not been adopted). Carbon dioxide emissions, health impacting exposures (air pollution, noise and physical activity), health (cardiovascular, respiratory, cancer and leukaemia) and wellbeing (including noise related wellbeing, overall wellbeing, economic wellbeing and inequalities) were modelled. The scenarios were developed from corresponding known levels in 2010 and pre-existing exposure response functions. Additionally there were literature reviews, three longitudinal observational studies and two cross sectional surveys.ResultsThere are four key findings. Firstly introduction of electric cars may confer some small health benefits but it would be unwise for a city to invest in electric vehicles unless their power generation fuel mix generates fewer emissions than petrol and diesel. Second, adopting policies to reduce private car use may have benefits for carbon dioxide reduction and positive health impacts through reduced noise and increased physical activity. Third, the benefits of carbon dioxide reduction from increasing housing efficiency are likely to be minor and co-benefits for health and wellbeing are dependent on good air exchange. Fourthly, although heating dwellings by in-home biomass burning may reduce carbon dioxide emissions, consequences for health and wellbeing were negative with the technology in use in the cities studied.ConclusionsThe climate-change reduction policies reduced CO2 emissions (the most common greenhouse gas) from cities but impact on global emissions of CO2 would be more limited due to some displacement of emissions. The health and wellbeing impacts varied and were often limited reflecting existing relatively high quality of life and environmental standards in most of the participating cities; the greatest potential for future health benefit occurs in less developed or developing countries.

Building-related health impacts in European and Chinese cities

BackgroundPublic health is often affected by societal decisions that are not primarily about health. Climate change mitigation requires intensive actions to minimise greenhouse gas emissions in the future. Many of these actions take place in cities due to their traffic, buildings, and energy consumption. Active climate mitigation policies will also, aside of their long term global impacts, have short term local impacts, both positive and negative, on public health.Our main objective was to develop a generic open impact model to estimate health impacts of emissions due to heat and power consumption of buildings. In addition, the model should be usable for policy comparisons by non-health experts on city level with city-specific data, it should give guidance on the particular climate mitigation questions but at the same time increase understanding on the related health impacts and the model should follow the building stock in time, make comparisons between scenarios, propagate uncertainties, and scale to different levels of detail.We tested The functionalities of the model in two case cities, namely Kuopio and Basel. We estimated the health and climate impacts of two actual policies planned or implemented in the cities. The assessed policies were replacement of peat with wood chips in co-generation of district heat and power, and improved energy efficiency of buildings achieved by renovations.ResultsHealth impacts were not large in the two cities, but also clear differences in implementation and predictability between the two tested policies were seen. Renovation policies can improve the energy efficiency of buildings and reduce greenhouse gas emissions significantly, but this requires systematic policy sustained for decades. In contrast, fuel changes in large district heating facilities may have rapid and large impacts on emissions. However, the life cycle impacts of different fuels is somewhat an open question.ConclusionsIn conclusion, we were able to develop a practical model for city-level assessments promoting evidence-based policy in general and health aspects in particular. Although all data and code is freely available, implementation of the current model version in a new city requires some modelling skills.