title: Maternal antioxidants prevent β-cell apoptosis and promote formation of dual hormone-expressing endocrine cells in male offspring following fetal and neonatal nicotine exposure.
abstract: BACKGROUND
  Fetal and neonatal nicotine exposure causes β-cell oxidative stress and apoptosis in neonates, leading to adult-onset dysglycemia. The aim of the present study was to determine whether an antioxidant intervention could prevent nicotine-induced β-cell loss.
  
  
  METHODS
  Nulliparous female Wistar rats received daily subcutaneous injections of either saline or nicotine bitartrate (1.0 mg/kg per day) for 2 weeks prior to mating until weaning. Nicotine-exposed dams received either normal chow or diet containing antioxidants (1000 IU/kg vitamin E, 0.25% w/w coenzyme Q10, and 0.1% w/w α-lipoic acid) during mating, pregnancy, and lactation; saline-exposed dams received normal chow. Pancreatic tissue was collected from male offspring at 3 weeks of age to measure β-cell fraction, apoptosis, proliferation, and the presence of cells coexpressing insulin and glucagon.
  
  
  RESULTS
  The birth weight of offspring born to nicotine-exposed dams was significantly reduced in those receiving dietary antioxidants compared with those fed normal chow. Most interestingly, the antioxidant intervention to nicotine-exposed dams prevented the β-cell loss and apoptosis observed in nicotine-exposed male offspring whose mothers did not receive antioxidants. Male pups born to nicotine-treated mothers receiving antioxidants also had a tendency for increased β-cell proliferation and a significant increase in islets containing insulin/glucagon bihormonal cells compared with the other two treatment groups.
  
  
  CONCLUSIONS
  The present study demonstrates that exposure to maternal antioxidants protects developing β-cells from the damaging effects of nicotine, thus preserving β-cell mass.
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Bruin
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Woynillowicz
authors.forename: Bart P
authors.initials: BP
authors.lastname: Hettinga
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Morrison
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000633:toxicity; D005934:Glucagon / Q000378:metabolism; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014886:Weaning
chemical_list: D000975:Antioxidants; D005731:Ganglionic Stimulants; D007328:Insulin; D009538:Nicotine; D005934:Glucagon