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

Abstract

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.

Human Preadipocytes Differentiated under Hypoxia following PCB126 Exposure during Proliferation: Effects on Differentiation, Glucose Uptake and Adipokine Profile

“…However, the visual examination of the cultures ( Figure 1 ) did not support a substantial difference in cell number between cultures initially exposed to DMSO and those exposed to PCB126. Another possible explanation for the decrease in ATP levels observed in cells exposed to PCB126 before differentiation could reside in the fact that POPs have been shown to impair mitochondrial oxygen consumption and ATP production, especially in the longer term, in vivo and in vitro [ 54 , 55 , 56 ]. While further investigations are required to explain the observed delayed decrease in ATP levels 14 days following PCB126 exposure, media LDH activity, cellular ADP/ATP ratio and visual examination strongly suggest that the cells’ viability was not compromised.…”

Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?

“…Recently, chronic exposure to low‐dose POPs has been linked to the risk of many chronic diseases including type 2 diabetes mellitus and cardiovascular diseases in the general population 3 , 4 . Although high doses of individual compounds belonging to POPs are well‐known mitochondrial toxins, a recent human and in vitro study demonstrated that even low‐dose POPs can impair mitochondrial function through the impairment of oxidative phosphorylation 5 . Therefore, chronic exposure to low‐dose POPs might be involved in the development of a wide range of mitochondrial dysfunction‐related diseases.…”

Obesity Paradox in Sepsis: Role of Adipose Tissue in Storing Mitochondrial Toxins

“…While early toxicological studies have primarily focused on acute chemical-induced mitochondrial toxicity at high doses, recent research highlighted the adverse effects of chronic exposure to low doses. Such exposure can lead to gradual mitochondrial dysfunction, especially by disrupting oxidative phosphorylation within the electron transport chain (6).…”

“…In addition, adipose tissue also secretes cytokines, such as adiponectin and leptin. These have anti-inflammatory effects and may help to counteract the inflammatory response in sepsis (6). Furthermore, obesity presents a "preconditioning" effect against the proinflammatory cascade.…”