title: Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats.
abstract: OBJECTIVE
  Chemotherapeutic agents induce small intestinal mucositis that is characterized structurally by crypt loss and villus atrophy and functionally by absorptive and barrier impairments. We studied the effect of selected individual vitamins and multiple-vitamin mixture supplementation in modulating cisplatin-induced intestinal damage and apoptosis.
  
  
  METHODS
  Thirty-six male Wistar/NIN rats 20 wk old and fed the control diet (AIN-93G) were randomly divided into six groups. Five groups were administered cisplatin (2.61 mg/kg of body weight) once a week for 3 wk and were concomitantly provided the control diet or riboflavin, folate, α- tocopherol, or a multiple-vitamin mixture supplemented diet. The sixth group served as a control for cisplatin and received saline as the vehicle. Intestinal epithelial cell apoptosis was monitored by morphometry, M30 staining, DNA fragmentation, and caspase-3 activity. Functional and structural integrities were determined by measuring activities of alkaline phosphatase and lysine ala-dipeptidyl aminopeptidase and the villus height/crypt depth ratio. Oxidative burden was assessed as the formation of thiobarbituric acid-reactive substances and protein carbonyls. Plasma levels of selected vitamins were also measured.
  
  
  RESULTS
  Cisplatin administration significantly increased intestinal apoptosis in the villus and crypt regions that correlated with increased oxidative damage, decreased Bcl-2/Bax, and compromised functional integrity. Riboflavin, folate, and the multiple-vitamin mixture supplementation attenuated the cisplatin-induced increase in apoptotic indices, with a decrease in oxidative burden, increased Bcl-2/Bax, and improved functional and structural integrities. The α-tocopherol supplementation, although effective in attenuating oxidative stress and improving functional integrity, failed to lower the apoptotic indices.
  
  
  CONCLUSIONS
  Riboflavin, folate, and the multiple-vitamin supplementation proved to be more efficacious in attenuating the cisplatin-induced intestinal damage and associated changes in apoptosis.
authors.affiliation: Pathology Division, National Institute of Nutrition, Hyderabad, Andhra Pradesh, India. bodigavijayasri@gmail.com
authors.forename: Vijaya Lakshmi
authors.initials: VL
authors.lastname: Bodiga
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Bodiga
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Surampudi
authors.forename: Sesikeran
authors.initials: S
authors.lastname: Boindala
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Putcha
authors.forename: Balakrishna
authors.initials: B
authors.lastname: Nagalla
authors.forename: Kalyanasundaram
authors.initials: K
authors.lastname: Subramaniam
authors.forename: Raghunath
authors.initials: R
authors.lastname: Manchala
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D019587:Dietary Supplements; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005492:Folic Acid / Q000008:administration & dosage; D007422:Intestines / Q000166:cytology* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012256:Riboflavin / Q000008:administration & dosage; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage*; D024502:alpha-Tocopherol / Q000008:administration & dosage; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D014815:Vitamins; D051028:bcl-2-Associated X Protein; D005492:Folic Acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D024502:alpha-Tocopherol; D002945:Cisplatin; D012256:Riboflavin