Placental mitochondrial DNA content and particulate air pollution during in utero life.

BACKGROUND: Studies emphasize the importance of particulate matter (PM) in the formation of reactive oxygen species and inflammation. We hypothesized that these processes can influence mitochondrial function of the placenta and fetus. OBJECTIVE: We investigated the influence of PM10 exposure during pregnancy on the mitochondrial DNA content (mtDNA content) of the placenta and umbilical cord blood. METHODS: DNA was extracted from placental tissue (n = 174) and umbilical cord leukocytes (n = 176). Relative mtDNA copy numbers (i.e., mtDNA content) were determined by real-time polymerase chain reaction. Multiple regression models were used to link mtDNA content and in utero exposure to PM10 over various time windows during pregnancy. RESULTS: In multivariate-adjusted analysis, a 10-µg/m³ increase in PM10 exposure during the last month of pregnancy was associated with a 16.1% decrease [95% confidence interval (CI): -25.2, -6.0%, p = 0.003] in placental mtDNA content. The corresponding effect size for average PM10 exposure during the third trimester was 17.4% (95% CI: -31.8, -0.1%, p = 0.05). Furthermore, we found that each doubling in residential distance to major roads was associated with an increase in placental mtDNA content of 4.0% (95% CI: 0.4, 7.8%, p = 0.03). No association was found between cord blood mtDNA content and PM10 exposure. CONCLUSIONS: Prenatal PM10 exposure was associated with placental mitochondrial alterations, which may both reflect and intensify oxidative stress production. The potential health consequences of decreased placental mtDNA content in early life must be further elucidated.

The association between urinary kidney injury molecule 1 and urinary cadmium in elderly during long-term, low-dose cadmium exposure: a pilot study.

BACKGROUND: Urinary kidney injury molecule 1 is a recently discovered early biomarker for renal damage that has been proven to be correlated to urinary cadmium in rats. However, so far the association between urinary cadmium and kidney injury molecule 1 in humans after long-term, low-dose cadmium exposure has not been studied. METHODS: We collected urine and blood samples from 153 non-smoking men and women aged 60+, living in an area with moderate cadmium pollution from a non-ferrous metal plant for a significant period. Urinary cadmium and urinary kidney injury molecule 1 as well as other renal biomarkers (alpha1-microglobulin, beta2-microglobulin, blood urea nitrogen, urinary proteins and microalbumin) were assessed. RESULTS: Both before (r = 0.20; p = 0.01) and after (partial r = 0.32; p < 0.0001) adjustment for creatinine, age, sex, past smoking, socio-economic status and body mass index, urinary kidney injury molecule 1 correlated with urinary cadmium concentrations. No significant association was found between the other studied renal biomarkers and urinary cadmium. CONCLUSIONS: We showed that urinary kidney injury molecule 1 levels are positively correlated with urinary cadmium concentration in an elderly population after long-term, low-dose exposure to cadmium, while other classical markers do not show an association. Therefore, urinary kidney injury molecule 1 might be considered as a biomarker for early-stage metal-induced kidney injury by cadmium.

Public health importance of triggers of myocardial infarction: a comparative risk assessment.

BACKGROUND: Acute myocardial infarction is triggered by various factors, such as physical exertion, stressful events, heavy meals, or increases in air pollution. However, the importance and relevance of each trigger are uncertain. We compared triggers of myocardial infarction at an individual and population level. METHODS: We searched PubMed and the Web of Science citation databases to identify studies of triggers of non-fatal myocardial infarction to calculate population attributable fractions (PAF). When feasible, we did a meta-regression analysis for studies of the same trigger. FINDINGS: Of the epidemiologic studies reviewed, 36 provided sufficient details to be considered. In the studied populations, the exposure prevalence for triggers in the relevant control time window ranged from 0.04% for cocaine use to 100% for air pollution. The reported odds ratios (OR) ranged from 1.05 to 23.7. Ranking triggers from the highest to the lowest OR resulted in the following order: use of cocaine, heavy meal, smoking of marijuana, negative emotions, physical exertion, positive emotions, anger, sexual activity, traffic exposure, respiratory infections, coffee consumption, air pollution (based on a difference of 30 µg/m3 in particulate matter with a diameter <10 µm [PM10]). Taking into account the OR and the prevalences of exposure, the highest PAF was estimated for traffic exposure (7.4%), followed by physical exertion (6.2%), alcohol (5.0%), coffee (5.0%), a difference of 30 µg/m3 in PM10 (4.8%), negative emotions (3.9%), anger (3.1%), heavy meal (2.7%), positive emotions (2.4%), sexual activity (2.2%), cocaine use (0.9%), marijuana smoking (0.8%) and respiratory infections (0.6%). Interpretation In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of myocardial infarction, it is of similar magnitude (PAF 5-7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance. FUNDING: The research on air pollution and health at Hasselt University is supported by a grant from the Flemish Scientific Fund (FWO, Krediet aan navorsers/G.0873.11), tUL-impulse financing, and bijzonder onderzoeksfonds (BOF) and at the Katholieke Universiteit Leuven by the sustainable development programme of BELSPO (Belgian Science Policy).

Cadmium exposure in the population: from health risks to strategies of prevention.

We focus on the recent evidence that elucidates our understanding about the effects of cadmium (Cd) on human health and their prevention. Recently, there has been substantial progress in the exploration of the shape of the Cd concentration-response function on osteoporosis and mortality. Environmental exposure to Cd increases total mortality in a continuous fashion without evidence of a threshold, independently of kidney function and other classical factors associated with mortality including age, gender, smoking and social economic status. Pooled hazard rates of two recent environmental population based cohort studies revealed that for each doubling of urinary Cd concentration, the relative risk for mortality increases with 17% (95% CI 4.2-33.1%; P < 0.0001). Tubular kidney damage starts at urinary Cd concentrations ranging between 0.5 and 2 µg urinary Cd/g creatinine, and recent studies focusing on bone effects show increased risk of osteoporosis even at urinary Cd below 1 µg Cd/g creatinine. The non-smoking adult population has urinary Cd concentrations close to or higher than 0.5 µg Cd/g creatinine. To diminish the transfer of Cd from soil to plants for human consumption, the bioavailability of soil Cd for the plants should be reduced (external bioavailability) by maintaining agricultural and garden soils pH close to neutral (pH-H(2)O of 7.5; pH-KCL of 6.5). Reducing the systemic bioavailability of intestinal Cd can be best achieved by preserving a balanced iron status. The latter might especially be relevant in groups with a lower intake of iron, such as vegetarians, and women in reproductive phase of life. In exposed populations, house dust loaded with Cd is an additional relevant exposure route. In view of the insidious etiology of health effects associated with low dose exposure to Cd and the current European Cd intake which is close to the tolerable weekly intake, one should not underestimate the importance of the recent epidemiological evidence on Cd toxicity as to its medical and public health implications.

Cadmium stress: an oxidative challenge.

At the cellular level, cadmium (Cd) induces both damaging and repair processes in which the cellular redox status plays a crucial role. Being not redox-active, Cd is unable to generate reactive oxygen species (ROS) directly, but Cd-induced oxidative stress is a common phenomenon observed in multiple studies. The current review gives an overview on Cd-induced ROS production and anti-oxidative defense in organisms under different Cd regimes. Moreover, the Cd-induced oxidative challenge is discussed with a focus on damage and signaling as downstream responses. Gathering these data, it was clear that oxidative stress related responses are affected during Cd stress, but the apparent discrepancies observed in between the different studies points towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress. This information is essential in order to reveal the exact role of Cd-induced oxidative stress in the modulation of downstream responses under a diverse array of conditions.