title: Synergistic protective effect of folic acid and vitamin B12 against nicotine-induced oxidative stress and apoptosis in pancreatic islets of the rat.
abstract: BACKGROUND
  Nicotine is an abundant and most significant component of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury, although effects of smoking on endocrine pancreas are still controversial.
  
  
  OBJECTIVE
  We examined the impact and underlying mechanisms of action of folic acid and vitamin B12 on nicotine-induced damage in pancreatic islets of rats.
  
  
  METHODS
  Male Wistar rats were treated with nicotine (3 mg/kg body weight/d, intraperitonealy) with or without folic acid (36 µg/kg body weight/d, orally) and vitamin B12 (0.63 µg/kg body weight/d, orally) for 21 d. Fasting blood glucose, oral glucose tolerance test, HBA1c, insulin, oxidative stress parameters, proinflammatory cytokines, and CRP level were measured. Histological evaluation, TUNEL assay, and immunohistochemical staining of NF-κB and caspase-3 were also performed.
  
  
  RESULTS
  Folic acid and vitamin B12 blunted the nicotine-induced impairment in fasting blood glucose (51-56% recovery), HbA1c (64-76% recovery), oral glucose tolerance, insulin level (23-40% recovery), and islet cell counts (26-74% recovery) in rats. Moreover, folic acid in combination with vitamin B12 also attenuated the nicotine-induced changes in markers of oxidative stress (17-88% recovery), TNF-α (40-99% recovery), and IL-6 level (47-65% recovery), CRP level (59-73% recovery), expression of NF-κB and caspase-3, and apoptosis in pancreatic islet cells.
  
  
  CONCLUSIONS
  The present study shows that folic acid and vitamin B12 supplementation can reduce nicotine-induced impairment in glucose homeostasis and apoptosis and damage of pancreatic islet cells by modulating oxidative stress, levels of proinflammatory cytokines, and expression of NF-κB.
authors.affiliation: a Department of Physiology , Serampore College , Serampore, Hooghly , West Bengal , India .
authors.forename: Ankita
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: a Department of Physiology , Serampore College , Serampore, Hooghly , West Bengal , India .
authors.forename: Shilpi K
authors.initials: SK
authors.lastname: Prasad
authors.affiliation: b Drug Development Division , Indian Institute of Chemical Biology , Jadavpur , Kolkata , India , and.
authors.forename: Swagata
authors.initials: S
authors.lastname: Pal
authors.affiliation: a Department of Physiology , Serampore College , Serampore, Hooghly , West Bengal , India .
authors.forename: Bithin
authors.initials: B
authors.lastname: Maji
authors.affiliation: c Department of Physiology , Hooghly Mohsin College , Hooghly , West Bengal , India.
authors.forename: Alak K
authors.initials: AK
authors.lastname: Syamal
authors.affiliation: a Department of Physiology , Serampore College , Serampore, Hooghly , West Bengal , India .
authors.forename: Sandip
authors.initials: S
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D005492:Folic Acid / Q000008:administration & dosage*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014805:Vitamin B 12 / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D009538:Nicotine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Islet cell; nutritional intervention; proinflammatory cytokines