Low-dose Persistent Organic Pollutants Research Articles

Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence.

BackgroundChronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.MethodsSerum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p′-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells.ResultsThe association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels.ConclusionThe findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

Can Habitual Exercise Help Reduce Serum Concentrations of Lipophilic Chemical Mixtures? Association between Physical Activity and Persistent Organic Pollutants.

BackgroundLow-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs), have emerged as a new risk factor of many chronic diseases. As serum concentrations of POPs in humans are mainly determined by both their release from adipose tissue to circulation and their elimination from circulation, management of these internal pathways may be important in controlling the serum concentrations of POPs. As habitual physical activity can increase the elimination of POPs from circulation, we evaluated whether chronic physical activity is related to low serum POP concentrations.MethodsA cross-sectional study of 1,850 healthy adults (age ≥20 years) without cardio-metabolic diseases who participated in the U.S. National Health and Nutrition Examination Survey 1999 to 2004 was conducted. Information on moderate or vigorous leisure-time physical activity was obtained based on questionnaires. Serum concentrations of OCPs and polychlorinated biphenyls were investigated as typical POPs.ResultsSerum concentrations of OCPs among physically active subjects were significantly lower than those among physically inactive subjects (312.8 ng/g lipid vs. 538.0 ng/g lipid, P<0.001). This difference was maintained after adjustment for potential confounders. When analyses were restricted to physically active subjects, there were small decreases in the serum concentrations of OCPs with increasing duration of physical activity, showing a curvilinear relationship over the whole range of physical activity (Pquadratic <0.001). In analyses stratified by age, sex, body mass index, and smoking status, a strong inverse association was similarly observed among all subgroups.ConclusionPhysical activity may assist in decreasing serum concentrations of lipophilic chemical mixtures such as OCPs.

Perfluorooctane sulfonate enhances mRNA expression of PPARγ and ap2 in human mesenchymal stem cells monitored by long-retained intracellular nanosensor

Perfluorooctane sulfonate (PFOS) has been widely used as a surface coating for household products. It still exists in living environments despite being restricted, due to its bioaccumulation and long half-life. Studies have shown that PFOS has the ability to induce adipogenic differentiation of human cells. Human mesenchymal stem cells (hMSCs) distributed within the adipose tissue might be a potential target of accumulated PFOS. However, traditional end-point toxicity assays failed to examine the subtle changes of cellular function exposed to low-dose persistent organic pollutants in real time. In the present work, highly sensitive and long-retained (more than 30 days) fluorescence based polymeric nanosensors were developed and employed for real-time assessment of cellular functions. hMSCs were engineered with sensor molecules encapsulated poly (lactic-co-glycolic acid) (PLGA) particles. Once internalized by hMSCs, PLGA particles continuously release and replenish sensor molecules to cytoplasm, resulting in prolonged fluorescence signal against photo bleaching and dilution by exocytosis. With this method, the dynamic changes of viability, ROS induction, and adipogenic differentiation related mRNA expression of hMSCs were monitored. PFOS with the concentration as low as 0.1 μM can induce cellular ROS and enhance the PPARγ and ap2 mRNA expression, suggesting the effect on promoting adipogenic differentiation of hMSCs.

Is dietary macronutrient intake associated with serum concentrations of organochlorine pesticides in humans?

In the general population, chronic exposure to low-dose persistent organic pollutants (POPs), particularly organochlorine pesticides (OCPs), has been recently linked to many chronic diseases. Widespread contamination of the food chain and human adipose tissue has made avoiding exposure to these chemicals impossible; thus, alternative strategies for decreasing the chemical burden must be investigated. Recently, macronutrient intake was found to significantly modify the toxicokinetics of POPs in animal experimental studies. Thus, we evaluated whether macronutrient intake was related to serum concentrations of OCPs in healthy adults without cardio-metabolic diseases. Subjects included 1,764 adults, aged 20 years or above, who participated in the National Health and Nutrition Examination Survey 1999–2004. Macronutrient intake was assessed based on a 24-h dietary recall interview. Six individual OCPs commonly detected among the general population were evaluated as markers of OCPs and other coexisting lipophilic chemicals stored in adipose tissue and released into circulation. High fat intake was associated with lower concentrations of OCPs, while high carbohydrate intake showed the opposite result. When three types of fats were individually evaluated, both saturated fatty acids and monounsaturated fatty acids, but not polyunsaturated fatty acids, were inversely associated with serum concentrations of OCPs. Adjustment for possible confounders did not change the results. When stratified by age, gender, body mass index, and physical activity, these associations were similar in most subgroups. Thus, similar to the findings observed in animal experimental studies, a moderate-fat diet with low carbohydrate intake was related to low serum concentrations of OCPs in humans. Although these findings need to be replicated, changing dietary macronutrient intake can be investigated as a practical strategy for dealing with unavoidable lipophilic chemical mixtures such as OCPs in modern society.

Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study.

BackgroundLow-dose persistent organic pollutants (POPs) have recently been linked to immunosenescence, a key mechanism in carcinogenesis, as well as many aging-related chronic diseases. Since feces are the main excretion route of POPs, the large intestine is a potential target organ for these pollutants. We performed a case-control study to evaluate whether exposure to low-dose POPs is related to the risk of colorectal polyps and cancer.MethodsA total of 277 participants were recruited from one hospital: 99 cancer patients, 102 polyp patients, and 76 control subjects. As typical examples of POPs, we measured the serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs).ResultsAcross the tertiles of the summary measure of POPs, the adjusted odds ratios (ORs) of colorectal polyps and cancer were 2.8 (1.2–6.8) (Ptrend = 0.01) and 3.0 (1.0–8.8) (Ptrend = 0.02), respectively, for subjects in the highest tertile. When OCPs and PCBs were analyzed separately, OCPs were linked to an increased risk of both polyps and cancer; the adjusted ORs were 2.3 (0.9–5.7) (Ptrend = 0.05) for polyps and 3.6 (1.1–11.8) (Ptrend< 0.01) for cancer. However, PCBs were only significantly associated with a high risk of polyps but not cancer; the adjusted OR was 2.8 (1.2–6.6) (Ptrend = 0.01).ConclusionChronic exposure to low-dose POPs may be associated with an increased risk of colorectal polyps and cancer. Our findings suggest the carcinogenic potential of strong lipophilic chemical mixtures such as POPs which are accumulated in adipose tissue, released to circulation, and eliminated through feces.

Persistent Organic Pollutants and Type 2 Diabetes: A Critical Review of Review Articles.

Low dose persistent organic pollutants (POPs) have emerged as a new risk for type 2 diabetes (T2D). Despite substantial evidence from human and experimental studies, there are several critical issues which have not been properly addressed by POPs researchers. First, as POPs exist as mixtures, findings about POPs from human studies should be interpreted from the viewpoint of lipophilic chemical mixtures which include both measured and unmeasured POPs. Second, as POPs can directly reduce insulin secretion of beta cells, the role of POPs may be more prominent in the development of beta-cell dysfunction-dominant T2D rather than insulin resistance-dominant T2D. Third, there are multidimensional interrelationships between POPs and adipose tissue. Even though POPs are now considered as a new risk factor for T2D, independent of obesity, POPs and obesity are mechanistically linked to each other. POPs are involved in key mechanisms linking obesity and T2D, such as chronic inflammation of adipose tissue and lipotoxicity with ectopic fat accumulation. Also, POPs can explain puzzling human findings which suggest benefits of obesity because healthy adipose tissue can be protective by reducing the amount of POPs reaching other organs. Fourth, non-linear dose-response relationships between POPs and T2D are biologically possible. Although POPs are well-known endocrine disrupting chemicals (EDCs), mitochondrial dysfunction may be a more plausible mechanism due to unpredictability of EDC mixtures. As adipose tissue plays a role as an internal exposure source of POPs, how to manage POPs inside us may be essential to protect against harms of POPs.

Deleterious effect of low-dose persistent organic pollutants on insulin secretion in pancreatic [beta]-cell

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Low-Dose Persistent Organic Pollutants Impair Insulin Secretory Function of Pancreatic β-Cells: Human and In Vitro Evidence.

Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor for type 2 diabetes. We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of β-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 adults without diabetes. Mathematical model-based insulin secretion indices were estimated by using a 2-h seven-sample oral glucose tolerance test. Insulin secretion by INS-1E β-cells was measured after 48 h of treatment with three OCPs or one PCB mixture. Static second-phase insulin secretion significantly decreased with increasing serum concentrations of OCPs. Adjusted means were 63.2, 39.3, 44.1, 39.3, 39.7, and 22.3 across six categories of a summary measure of OCPs (Ptrend = 0.02). Dynamic first-phase insulin secretion remarkably decreased with increasing concentrations of OCPs among only insulin-sensitive individuals (Ptrend = 0.02); the insulin levels among individuals with high OCPs were ∼30% of those with low OCPs. Compared with OCPs, PCBs showed weaker associations. The decreased insulin secretion by INS-1E β-cells was observed for even 1 pmol/L OCP. The data from human and in vitro cell experiments suggest that chronic exposure to low-dose POPs, especially OCPs, can induce pancreatic β-cell dysfunction.

The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms.

BackgroundPersistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to uncover the effects of POPs on the endocrine and nervous systems and on cancer, few focus on the relationship between low-dose POPs and public health. Here, we attempt to determine the relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation.MethodsWe recruited 121 subjects who visited Kyungpook National University Medical Center for health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls (PCBs) and 23 types of organochlorine pesticides (OCP). Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms.ResultsBased on our results, abdominal discomfort showed an inverse relationship with several PCBs and an inverted U-shaped relationship with several other OCPs including pp-DDD and pp-DDT. The effects of pp-DDD and pp-DDT on abdominal discomfort were similar to those of OCPs on obesity and metabolic syndrome.ConclusionOur results suggest that mild and unspecified gastrointestinal symptoms with no clear causes could be related to POP levels.

The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms.

BackgroundPersistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to reveal the effects of POPs on the endocrine and nervous system and on cancer, few studies focus on the relationship between low-dose POPs and public health. We attempted to find a relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation.MethodsWe recruited 121 subjects who visited Kyungpook National University Hospital for a health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls and 23 types of organochlorine pesticides. Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms.ResultsOur results showed that abdominal discomfort had an inverse relationship with several polychlorinated biphenyls. Moreover, an inverted U-shaped relationship was observed between abdominal discomfort and several other organochlorine pesticides including p,p'-dichlorodiphenyldichloroethane and p,p'-dichlorodiphenyltrichloroethane, and the effects of these pesticides on abdominal discomfort were similar to that of organochlorine pesticides on obesity and metabolic syndrome.ConclusionOur results suggest that mild and unspecified gastrointestinal symptoms with no clear cause could be related to POPs levels.

Low-dose persistent organic pollutants increased telomere length in peripheral leukocytes of healthy Koreans

Although shortened telomeres have been found in many cancers, elongated telomere length has been observed as an early response after low-dose treatment with various chemical carcinogens in vitro and animal experiments, suggesting low-dose exposure to carcinogenic chemicals may function as a tumour promoter at the very early stage of carcinogenesis in humans. This cross-sectional study was performed to examine whether low-dose exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that mainly bioaccumulate in adipose tissue, is associated with telomere length of peripheral blood leukocytes in apparently healthy persons. Telomere length was measured using quantitative polymerase chain reaction method in 84 apparently healthy Koreans. Among various POPs, serum concentrations of organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers were measured. Most OC pesticides and PCBs were positively and significantly associated with telomere length with correlation coefficients from about +0.25 to +0.35. The strongest associations were observed with p,p'-dichlorodiphenyldichloroethylene, PCB99, PCB153, PCB180, PCB183 and PCB187. When we examined adjusted means of telomere length by quintiles of POPs, the steeper increases of telomere length tended to be observed within relatively lower ranges of POPs. Besides serum concentrations of POPs, none of the other variables studied, including age, were associated with telomere length in this study. We found that telomere length was increasing across low doses of exposure to POPs in which the majority of study subjects were found, suggesting that low-dose POPs may act as a tumour promoter in carcinogenesis in humans.