Acute exposure to environmentally relevant levels of DDT alters muscle mitochondrial function in vivo in rats but not in vitro in L6 myotubes: A pilot study

• Published in: Toxicology Reports
• Main Authors: Chehade, Lucia, Khouri, Hannah, Malatier--Ségard, Julie, Caron, Audrey, Mauger, Jean-François, Chapados, Natalie Ann, Aguer, Céline
• Format: Text
• Language: English
• Published: Elsevier 2022
• Subjects: Regular Article; Canada; inuit
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956919/; http://www.ncbi.nlm.nih.gov/pubmed/35345859; https://doi.org/10.1016/j.toxrep.2022.03.004

Under insulin-stimulated conditions, skeletal muscle is the largest glucose consumer in the body. Mitochondrial dysfunction and damage to this tissue from oxidative stress are linked to the pathogenesis of type 2 diabetes. Environmental exposure to dichlorodiphenyltrichloroethane (DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has been associated with the incidence of type 2 diabetes as well as altered oxidative stress and mitochondrial dysfunction in non-muscle tissues. We hypothesized that energy metabolism and insulin sensitivity in skeletal muscle will be altered with exposure to DDT and DDE. In this pilot study, mitochondrial function was measured in permeabilized muscle fibers from Sprague-Dawley rats after one week of exposure to a single injection of DDT (40 μg/kg), a dose comparable to DDT levels in the diets of the Inuit of Northern Canada. The levels of oxidative phosphorylation chain complexes and ROS detoxification enzymes were measured in muscle tissue from these specimens. This acute in vivo exposure to DDT decreased muscle mitochondrial function by 45% without affecting the levels of mitochondrial oxidative phosphorylation chain complexes nor levels of ROS detoxification enzymes. To isolate the effects of DDT and DDE exposure on muscle, L6 myotubes were exposed to DDT or DDE (0, 10, 100, 1000, 10 000 nM) for 24 h. Only very high concentrations of DDT and DDE (1 000 – 10 000 nM) altered maximal respiration with only DDT altering basal glucose uptake in L6 myotubes. This did not alter levels of ROS detoxification enzymes or malondialdehyde (MDA) in L6 myotubes. Altogether, acute exposure to environmentally relevant doses of DDT resulted in muscle mitochondrial dysfunction in vivo in rats, but not when muscle cells were directly exposed to the pollutant or its metabolite.