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

• Published in: Diabetes & metabolism journal Vol. 46; no. 4; pp. 592 - 604
• Main Authors: Kim, Se-A, Lee, Hoyul, Park, Sung-Mi, Kim, Mi-Jin, Lee, Yu-Mi, Yoon, Young-Ran, Lee, Hyun-Kyung, Moon, Hyo-Bang, Lee, In-Kyu, Lee, Duk-Hee
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Diabetes Association / Daehan Dangnyobyeong Hakoe 01.07.2022; Korean Diabetes Association; 대한당뇨병학회
• Subjects: Adult; Bioenergetics; Blood platelets; Body mass index; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Environmental Exposure - adverse effects; Humans; Hypertension; Laboratories; Leukocytes; Leukocytes, Mononuclear - metabolism; mitochondria; Mitochondria - metabolism; Original; oxygen consumption; PCB; Persistent Organic Pollutants; Pesticides; Pollutants; Polychlorinated biphenyls; Polychlorinated Biphenyls - metabolism; Polychlorinated Biphenyls - toxicity; Respiration; 내과학; United States > US; Japan; Polychlorinated biphenyls; Oxygen consumption; Mitochondria; Persistent organic pollutants; Pesticides
• ISSN: 2233-6079; 2233-6087; 2233-6087
• DOI: 10.4093/dmj.2021.0132

Background: Chronic 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.Methods: Serum 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.Results: The 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.Conclusion: The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.