Abstract
In the past few years, polychlorinated biphenyls (PCBs), a class of environmental pollutants, have been associated with metabolism dysregulation. Muscle is one of the key regulators of metabolism because of its mass and its important role in terms of glucose consumption and glucose storage. It has been shown that muscle alterations, such as oxidative stress and mitochondrial dysfunction, contribute significantly to the development of metabolic diseases. No study has yet investigated the toxicological effect of PCBs on muscle mitochondrial function and oxidative stress in vivo. The aim of this study was to assess the effect of PCB126 in vivo exposure (single dose of 1.05 μmol/kg) on muscle mitochondrial function and oxidative stress in rats. PCB126-treated rats showed a marked increase in Cyp1a1 mRNA levels in skeletal muscles in association with a 40% reduction in state 3 oxygen consumption rate measured with complex I substrates in permeabilized muscle fibers. Furthermore, PCB126 exposure altered the expression of some enzymes involved in ROS detoxification such as catalase and glutaredoxin 2. Our results highlight for the first time a toxic effect of coplanar PCBs on skeletal muscle mitochondrial function and oxidative stress. This suggests that acute PCB exposure, by affecting muscle metabolism, could contribute to the development of metabolic disorders. Studies are needed to determine if lower-level but longer-term PCB exposure exhibits the same effect.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aguer C, Mercier J, Man CYW et al (2010) Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients. Diabetologia 53:1151–1163. https://doi.org/10.1007/s00125-010-1708-x
Aguer C, Fiehn O, Seifert EL, Bézaire V, Meissen JK, Daniels A, Scott K, Renaud JM, Padilla M, Bickel DR, Dysart M, Adams SH, Harper ME (2013) Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete β-oxidation. FASEB J 27:4213–4225. https://doi.org/10.1096/fj.13-234302
Aly HAA, Domènech O (2009) Aroclor 1254 induced cytotoxicity and mitochondrial dysfunction in isolated rat hepatocytes. Toxicology 262:175–183. https://doi.org/10.1016/j.tox.2009.05.018
Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW III, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119:573–581. https://doi.org/10.1172/JCI37048
Arsenescu V, Arsenescu RI, King V, Swanson H, Cassis LA (2008) Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ Health Perspect 116:761–768. https://doi.org/10.1289/ehp.10554
ATSDR (2000) Toxicological profile for polychlorinated biphenyls (PCBs). Atlanta,GA
Barazzoni R, Gortan Cappellari G, Ragni M, Nisoli E (2018) Insulin resistance in obesity: an overview of fundamental alterations. Eat Weight Disord 23:149–157. https://doi.org/10.1007/s40519-018-0481-6
Bonnard C, Durand A, Peyrol S, Chanseaume E, Chauvin MA, Morio B, Vidal H, Rieusset J (2008) Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J Clin Invest 118:789–800. https://doi.org/10.1172/JCI32601
Chapados NA, Boucher M-P (2017) Liver metabolic disruption induced after a single exposure to PCB126 in rats. Environ Sci Pollut Res Int 24:1854–1861. https://doi.org/10.1007/s11356-016-7939-8
Clerch LB, Wright A, Chung DJ, Massaro D (1996) Early divergent lung antioxidant enzyme expression in response to lipopolysaccharide. Am J Phys 271:L949–L954. https://doi.org/10.1152/ajplung.1996.271.6.L949
Cocco S, Secondo A, Del Viscovo A et al (2015) Polychlorinated biphenyls induce mitochondrial dysfunction in SH-SY5Y neuroblastoma cells. PLoS One 10:e0129481. https://doi.org/10.1371/journal.pone.0129481
Di Meo S, Iossa S, Venditti P (2017) Skeletal muscle insulin resistance: role of mitochondria and other ROS sources. J Endocrinol 233:R15–R42. https://doi.org/10.1530/JOE-16-0598
Ebner KV, Braselton WE (1987) Permeability changes in hepatic mitochondria and altered glucose and urea metabolism in aroclor 1254-treated rats. J Toxicol Environ Health 22:45–62. https://doi.org/10.1080/15287398709531050
Everett CJ, Frithsen IL, Diaz VA, Koopman RJ, Simpson WM Jr, Mainous AG III (2007) Association of a polychlorinated dibenzo-p-dioxin, a polychlorinated biphenyl, and DDT with diabetes in the 1999-2002 National Health and nutrition examination survey. Environ Res 103:413–418. https://doi.org/10.1016/j.envres.2006.11.002
Franco AA, Odom RS, Rando TA (1999) Regulation of antioxidant enzyme gene expression in response to oxidative stress and during differentiation of mouse skeletal muscle. Free Radic Biol Med 27:1122–1132. https://doi.org/10.1016/S0891-5849(99)00166-5
Frontera WR, Ochala J (2015) Skeletal muscle: a brief review of structure and function. Calcif Tissue Int 96:183–195. https://doi.org/10.1007/s00223-014-9915-y
Gadupudi GS, Elser BA, Sandgruber FA, Li X, Gibson-Corley KN, Robertson LW (2018) PCB126 inhibits the activation of AMPK-CREB signal transduction required for energy sensing in liver. Toxicol Sci 163:440–453. https://doi.org/10.1093/toxsci/kfy041
Gonzalez-Franquesa A, Patti M-E (2017) Insulin resistance and mitochondrial dysfunction. Adv Exp Med Biol 982:465–520. https://doi.org/10.1007/978-3-319-55330-6_25
Gutiérrez-Vázquez C, Quintana FJ (2018) Regulation of the immune response by the aryl hydrocarbon receptor. Immunity 48:19–33. https://doi.org/10.1016/j.immuni.2017.12.012
Ha KH, Kim SA, Lee YM et al (2018) Can persistent organic pollutants distinguish between two opposite metabolic phenotypes in lean Koreans? Diabetes Metab 44:168–171. https://doi.org/10.1016/j.diabet.2017.12.008
Harden FA, Toms LML, Paepke O, Ryan JJ, Müller JF (2007) Evaluation of age, gender and regional concentration differences for dioxin-like chemicals in the Australian population. Chemosphere 67:S318–S324. https://doi.org/10.1016/j.chemosphere.2006.05.146
Heindel JJ, Skalla LA, Joubert BR, Dilworth CH, Gray KA (2017) Review of developmental origins of health and disease publications in environmental epidemiology. Reprod Toxicol 68:34–48. https://doi.org/10.1016/j.reprotox.2016.11.011
Hennig B, Hammock BD, Slim R, Toborek M, Saraswathi V, Robertson LW (2002) PCB-induced oxidative stress in endothelial cells: modulation by nutrients. Int J Hyg Environ Health 205:95–102. https://doi.org/10.1078/1438-4639-00134
Hennig B, Ettinger AS, Jandacek RJ, Koo S, McClain C, Seifried H, Silverstone A, Watkins B, Suk WA (2007) Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases. Environ Health Perspect 115:493–495. https://doi.org/10.1289/ehp.9549
Hesselink MKC, Schrauwen-Hinderling V, Schrauwen P (2016) Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus. Nat Rev Endocrinol 12:633–645. https://doi.org/10.1038/nrendo.2016.104
Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948. https://doi.org/10.1038/nature04634
Imbeault P, Tremblay A, Simoneau J-A, Joanisse DR (2002) Weight loss-induced rise in plasma pollutant is associated with reduced skeletal muscle oxidative capacity. Am J Physiol Endocrinol Metab 282:E574–E579. https://doi.org/10.1152/ajpendo.00394.2001
Kim MJ, Pelloux V, Guyot E, Tordjman J, Bui LC, Chevallier A, Forest C, Benelli C, Clément K, Barouki R (2012) Inflammatory pathway genes belong to major targets of persistent organic pollutants in adipose cells. Environ Health Perspect 120:508–514. https://doi.org/10.1289/ehp.1104282
Kopec AK, Burgoon LD, Ibrahim-Aibo D, Burg AR, Lee AW, Tashiro C, Potter D, Sharratt B, Harkema JR, Rowlands JC, Budinsky RA, Zacharewski TR (2010) Automated dose-response analysis and comparative toxicogenomic evaluation of the hepatic effects elicited by TCDD, TCDF, and PCB126 in C57BL/6 mice. Toxicol Sci 118:286–297. https://doi.org/10.1093/toxsci/kfq236
Lai C (1996) Chronic exposure of neonatal cardiac myocytes to hydrogen peroxide enhances the expression of catalase. J Mol Cell Cardiol 28(5):1157–1163. https://doi.org/10.1006/jmcc.1996.0106
Lai IK, Dhakal K, Gadupudi GS, Li M, Ludewig G, Robertson LW, Olivier AK (2012) N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents. Toxicology 302:25–33. https://doi.org/10.1016/j.tox.2012.07.007
Li QQ, Loganath A, Chong YS (2006) Levels of persistent organic pollutant residues in human adipose and muscle tissues in Singapore. J Toxic Environ Health A 69(21):1927–1937. https://doi.org/10.1080/15287390600751306
Lu C, Wang Y, Sheng Z, Liu G, Fu Z, Zhao J, Zhao J, Yan X, Zhu B, Peng S (2010) NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats. Toxicol Appl Pharmacol 248:178–184. https://doi.org/10.1016/j.taap.2010.07.020
Mauger J-F, Nadeau L, Caron A, Chapados NA, Aguer C (2016) Polychlorinated biphenyl 126 exposure in L6 myotubes alters glucose metabolism: a pilot study. Environ Sci Pollut Res Int 23:8133–8140. https://doi.org/10.1007/s11356-016-6348-3
National Center for Environmental Health, Centers for Disease Control and Prevention CDC (2009) Fourth National Report on Human Exposure to Environmental Chemicals. Atlanta, GA
Newsome BJ, Petriello MC, Han SG, Murphy MO, Eske KE, Sunkara M, Morris AJ, Hennig B (2014) Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes. J Nutr Biochem 25:126–135. https://doi.org/10.1016/j.jnutbio.2013.10.003
Ounnas F, Privé F, Lamarche F, Salen P, Favier-Hininger I, Marchand P, le Bizec B, Venisseau A, Batandier C, Fontaine E, de Lorgeril M, Demeilliers C (2016) A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats. Chemosphere 161:80–88. https://doi.org/10.1016/j.chemosphere.2016.06.040
Parvez S, Evans AM, Lorber M, Hawkins BS, Swartout JC, Teuschler LK, Rice GE (2013) A sensitivity analysis using alternative toxic equivalency factors to estimate U.S. dietary exposures to dioxin-like compounds. Regul Toxicol Pharmacol 67:278–284. https://doi.org/10.1016/j.yrtph.2013.08.007
Ramadass P, Meerarani P, Toborek M, Robertson LW, Hennig B (2003) Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells. Toxicol Sci 76:212–219. https://doi.org/10.1093/toxsci/kfg227
Ricardo SD, Ding G, Eufemio M, Diamond JR (1997) Antioxidant expression in experimental hydronephrosis: role of mechanical stretch and growth factors. Am J Physiol Ren Physiol 272(6):F789–F798
Rocha de Oliveira C, Ceolin J, Rocha de Oliveira R, Gonçalves Schemitt E, Raskopf Colares J, de Freitas Bauermann L, Hilda Costabeber I, Morgan-Martins MI, Mauriz JL, da Silva J, Reyes JM, Possa Marroni N (2014) Effects of quercetin on polychlorinated biphenyls-induced liver injury in rats. Nutr Hosp 29:1141–1148. https://doi.org/10.3305/nh.2014.29.5.7362
Ruzzin J, Petersen R, Meugnier E, Madsen L, Lock EJ, Lillefosse H, Ma T, Pesenti S, Sonne SB, Marstrand TT, Malde MK, du ZY, Chavey C, Fajas L, Lundebye AK, Brand CL, Vidal H, Kristiansen K, Frøyland L (2010) Persistent organic pollutant exposure leads to insulin resistance syndrome. Environ Health Perspect 118:465–471. https://doi.org/10.1289/ehp.0901321
Salihovic S, Lampa E, Lindström G, Lind L, Lind PM, van Bavel B (2012) Circulating levels of persistent organic pollutants (POPs) among elderly men and women from Sweden: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Environ Int 44:59–67. https://doi.org/10.1016/j.envint.2012.01.011
Sanders JM, Burka LT, Smith CS, Black W, James R, Cunningham ML (2005) Differential expression of CYP1A, 2B, and 3A genes in the F344 rat following exposure to a polybrominated diphenyl ether mixture or individual components. Toxicol Sci 88:127–133. https://doi.org/10.1093/toxsci/kfi288
Shen K, Shen C, Yu J, Yu C, Chen L, Shi D, Chen Y (2011) PCB congeners induced mitochondrial dysfunction in Vero cells. J Hazard Mater 185:24–28. https://doi.org/10.1016/j.jhazmat.2010.08.061
Shen H, Li M, Wang B et al (2014) Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats. Environ Sci Pollut Res Int 21:6384–6399. https://doi.org/10.1007/s11356-013-1690-1
Singh I, Gulati S, Orak JK, Singh AK (1993) Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. Mol Cell Biochem 125:97–104. https://doi.org/10.1007/BF00936438
Slim R, Toborek M, Robertson LW, Lehmler HJ, Hennig B (2000) Cellular glutathione status modulates polychlorinated biphenyl-induced stress response and apoptosis in vascular endothelial cells. Toxicol Appl Pharmacol 166:36–42. https://doi.org/10.1006/taap.2000.8944
Srere PA (1969) Citrate synthase:[EC 4.1. 3.7. Citrate oxaloacetate-lyase (CoA-acetylating)]. In: Methods in enzymology, vol 13. Academic Press, p 3–11
Steinberg GR (2007) Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance. Cell Cycle 6:888–894. https://doi.org/10.4161/cc.6.8.4135
Uemura H, Arisawa K, Hiyoshi M, Satoh H, Sumiyoshi Y, Morinaga K, Kodama K, Suzuki TI, Nagai M, Suzuki T (2008) Associations of environmental exposure to dioxins with prevalent diabetes among general inhabitants in Japan. Environ Res 108:63–68. https://doi.org/10.1016/j.envres.2008.06.002
US EPA (2000) Exposure and human health reassessment of 2,3,7,8-tetrachlorodibenzo-P-dioxin (Tcdd) and related compounds: science advisory board (external review draft). U.S. Environmental Protection Agency, Washington, DC
US EPA (2003) Human exposures to CDD, CDF and PCB congeners. Exposure and human health reassessment of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) and related compounds 2. U.S. Environmental Protection Agency, Washington, DC
Wong MH, Armour MA, Naidu R, Man M (2012) Persistent toxic substances: sources, fates and effects. Rev Environ Health 27(4):207-213. https://doi.org/10.1515/reveh-2012-0040
Yao Y, Takasuga T, Masunaga S, Nakanishi J (2002) Detailed study on the levels of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in Yusho rice oil. Chemosphere 46:1461–1469
Zhong Y, Guo P, Wang X, An J (2015) Aroclor 1254 inhibits cell viability and induces apoptosis of human A549 lung cancer cells by modulating the intracellular Ca(2+) level and ROS production through the mitochondrial pathway. J Environ Sci Health A Tox Hazard Subst Environ Eng 50:806–813. https://doi.org/10.1080/10934529.2015.1019797
Zhou H, Qu Y, Wu H, Liao C, Zheng J, Diao X, Xue Q (2010) Molecular phylogenies and evolutionary behavior of AhR (aryl hydrocarbon receptor) pathway genes in aquatic animals: implications for the toxicology mechanism of some persistent organic pollutants (POPs). Chemosphere 78:193–205. https://doi.org/10.1016/j.chemosphere.2009.09.012
Zhu Y, Kalen AL, Li L, Lehmler HJ, Robertson LW, Goswami PC, Spitz DR, Aykin-Burns N (2009) Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure. Free Radic Biol Med 47:1762–1771. https://doi.org/10.1016/j.freeradbiomed.2009.09.024
Zurlo F, Larson K, Bogardus C, Ravussin E (1990) Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 86:1423–1427. https://doi.org/10.1172/JCI114857
Funding
This work was supported by operating funding from the Institut du Savoir Montfort - Recherche to CA, NSERC (Natural Sciences and Engineering Research Council of Canada) Discovery grants [grant numbers 2015-06263 to CA and 418312-2012 to NC], and Chemical Management Plan from Health Canada to EA. Undergraduate Research Opportunity Program (UROP) scholarship to CTL was provided by the University of Ottawa.
Author information
Authors and Affiliations
Contributions
Experiments were performed in Dr. Aguer’s laboratory at the Institut du Savoir Monfort - Recherche (Ottawa, ON, Canada), except for the q-PCR experiment that was performed in Dr. Atlas’s laboratory at Health Canada. Conception and design of the experiments: NC and CA; collection, assembly, analysis, and interpretation of data: CTL, LG, JFM, VP, ASN, NC, and CA; drafting the article or revising it critically for important intellectual content: CTL, LG, JFM, VP, EA, ASN, NC, and CA; approval of the final version: CTL, LG, JFM, VP, EA, ASN, NC and CA.
Corresponding author
Ethics declarations
The protocol was approved by the Animal Care Committee of the University of Ottawa (ME-2230) and performed in compliance with the Canadian council on Animal Care guidelines.
Conflict of interest
The authors declare that they have no competing interests.
Additional information
Responsible editor: Philippe Garrigues
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Tremblay-Laganière, C., Garneau, L., Mauger, JF. et al. Polychlorinated biphenyl 126 exposure in rats alters skeletal muscle mitochondrial function. Environ Sci Pollut Res 26, 2375–2386 (2019). https://doi.org/10.1007/s11356-018-3738-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-018-3738-8