title: Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats.
abstract: Perinatal smoke/nicotine exposure predisposes to chronic lung disease and morbidity. Mitochondrial abnormalities may contribute as the PPARγ pathway is involved in structural and functional airway deficits after perinatal nicotine exposure. We hypothesized perinatal nicotine exposure results in lung mitochondrial dysfunction that can be rescued by rosiglitazone (RGZ; PPARγ receptor agonist). Sprague-Dawley dams received placebo (CON), nicotine (NIC, 1 mg kg(-1)), or NIC + RGZ (3 mg kg(-1)) daily from embryonic day 6 to postnatal day 21. Parenchymal lung (~10 mg) was taken from adult male offspring for mitochondrial assessment in situ. ADP-stimulated O2 consumption was less in NIC and NIC + RGZ compared to CON (F[2,14] = 17.8; 4.5 ± 0.8 and 4.1 ± 1.4 vs. 8.8 ± 2.5 pmol s mg(-1); p < 0.05). The respiratory control ratio for ADP, an index of mitochondrial coupling, was reduced in NIC and remediated in NIC + RGZ (F[2,14] = 3.8; p < 0.05). Reduced mitochondrial oxidative capacity and abnormal coupling were evident after perinatal nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation.
authors.affiliation: Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA. dcannon@mail.sdsu.edu.|School of Exercise & Nutritional Sciences, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA. dcannon@mail.sdsu.edu.
authors.forename: Daniel T
authors.identifier: http://orcid.org/0000-0002-2175-3445
authors.initials: DT
authors.lastname: Cannon
authors.affiliation: Division of Neonatology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Neonatology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Sakurai
authors.affiliation: Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.|School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Rossiter
authors.affiliation: Division of Neonatology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019069:Cell Respiration / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D018811:Maternal Exposure; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D018722:Nicotinic Agonists; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009538:Nicotine