Toxicity of brominated flame retardants, BDE-47 and BDE-99 stems from impaired mitochondrial bioenergetics

Abstract

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants, and they have been detected in human blood, adipose tissue and breast milk, a consequence of their physicochemical and bioaccumulative properties, as well as their high environmental persistence. Many studies report liver toxicity related to exposure to PBDEs. In the present study, we investigated the toxicity of BDE-47 and BDE-99 at concentrations ranging from 0.1 to 50 µM in isolated rat liver mitochondria. We evaluated how incubation of a mitochondrial suspension with the PBDEs affected the mitochondrial inner membrane, membrane potential, oxygen consumption, calcium release, mitochondrial swelling, and ATP levels to find out whether the tested compound interfered with the bioenergetics of this organelle. Both PBDEs were toxic to mitochondria: BDE-47 and BDE-99 concentrations equal to or higher than 25 and 50 µM, respectively, modified all the parameters used to assess mitochondrial bioenergetics, which culminated in ATP depletion. These effects stemmed from the ability of both PBDEs to cause Membrane Permeability Transition (MPT) in mitochondria, which impaired mitochondrial bioenergetics. In particular, BDE-47, which has fewer bromine atoms in the molecule, can easily overcome biological membranes what would be responsible for the major negative effects exerted by this congener when compared with BDE-99.

• ATP depletion
• bioenergetics
• mitochondria
• PBDEs

Acknowledgements

The authors thank Professor Carlos Curti, PhD, Professor Luciane Carla Alberici, PhD, and the Biochemistry Laboratory of the Faculty of Pharmaceutical Sciences of Ribeirão Preto – USP/Brazil for technical support.

Declaration of interest

The authors report no declarations of interest. The authors thank for the financial support – grant #2009/06912-6 and #2012/04542-0 São Paulo Research Foundation (FAPESP).