title: α-tocopherol supplementation prevents lead acetate and hypoxia-induced hepatic dysfunction.
abstract: OBJECTIVE
  Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces oxidative damages. In this study, we investigated the exposure of chronic sustained hypoxia or lead acetate alone or in combination with or without supplementation of α-tocopherol on hepatic oxidative and nitrosative stress in rats.
  
  
  METHODS
  The rats weighing 165 ± 5 g were exposed to chronic sustained hypoxia (10% oxygen) or lead acetate (25 mg/kg of body weight, intraperitoneally) alone or in combination with or without supplementation of α-tocopherol (10 mg/100 g b.wt, intramuscularly). The body weight of all the rats was recorded on the day 1 of the treatment and the day of sacrifice. Serum lipid profile was estimated by using a biochemical analyzer. Oxidant and enzymatic antioxidants status was evaluated by using spectrophotometer. Serum levels of hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by using ELISA technique. Histopathological assessments of hepatic tissue were also done.
  
  
  RESULTS
  Exposure of both lead and hypoxia showed decreased body weight, altered serum lipid profile, oxidant and enzymatic antioxidants status, serum HIF-1α and VEGF concentrations. Simultaneous α-tocopherol supplementation showed beneficial effects to all these alterations. Histopathological observations also showed hepatic degenerative changes after lead or hypoxia exposure either alone or in combination, but remarkable improvement has been noticed after α-tocopherol supplementation.
  
  
  CONCLUSIONS
  Supplementation of α-tocopherol is beneficial to counter both lead acetate and hypoxia induced hepatic cytotoxicities possibly by reducing oxidative and nitrosative stress.
authors.affiliation: Department of Physiology, Shri B. M. Patil Medical College, Hospital and Research Centre, BLDE University, Bijapur, Karnataka, India.
authors.forename: Kusal K
authors.initials: KK
authors.lastname: Das
authors.affiliation: Department of Physiology, Al Ameen Medical College, Bijapur, Karnataka, India.
authors.forename: Jameel G
authors.initials: JG
authors.lastname: Jargar
authors.affiliation: Division of Cardiovascular and Diabetic Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9NL, UK.
authors.forename: Sikha
authors.initials: S
authors.lastname: Saha
authors.affiliation: Department of Pathology, Al Ameen Medical College, Bijapur, Karnataka, India.
authors.forename: Saeed M
authors.initials: SM
authors.lastname: Yendigeri
authors.affiliation: Defence Institute of Physiology and Allied Sciences, DRDO, Timarpur, New Delhi, India.
authors.forename: Shashi Bala
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D000860:Hypoxia / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood; D008055:Lipids / Q000097:blood; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009942:Organometallic Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008055:Lipids; D009942:Organometallic Compounds; D042461:Vascular Endothelial Growth Factor A; D024502:alpha-Tocopherol; C008261:lead acetate
keywords: hypoxia; lead acetate; nitrosative stress; oxidative stress; α-tocopherol