title: Impacts of ascorbic acid and thiamine supplementation at different concentrations on lead toxicity in testis.
abstract: BACKGROUND
  Lead is a ubiquitous environmental and industrial pollutant that may have toxic effects on the male reproductive system. We explored the mechanism and examine the impacts of combined administration of ascorbic acid and thiamine at different levels on apoptosis in the testes of lead-exposed mice.
  
  
  METHODS
  Seventy-five male mice were randomly divided into 5 groups (15 mice/group): control, lead-treated and vitamin-treated group (low, middle and high dose) with ascorbic acid (140, 420, 1260 mg/kg) and thiamine (10, 30, 90 mg/kg ) by oral gavage daily. All lead-exposed animals received 0.2% lead acetate in drinking water. DNA damage of testicular cells was assessed by SCGE; the levels of TGFbeta1 and caspase-3 were detected by immunohistochemistry; apoptotic cell was determined by TUNEL.
  
  
  RESULTS
  Compared with control group, the expressions of TGFbeta1 and caspase-3, apoptotic index (AI) and DNA damage were increased significantly in lead-exposed group (P<0.05). After intervention of low and middle doses vitamin, the incidence of DNA damage and the number of apoptotic cells in testis were obviously lower than the lead-exposed group (P<0.05) and the impaired tissues were ameliorative. However, simultaneous supplementation of ascorbic acid and thiamine at the highest dose promoted testicular cell apoptosis via increased expressions of TGFbeta1 and caspase-3.
  
  
  CONCLUSIONS
  The combination treatment with thiamine and ascorbic acid at lower doses effectively inhibited testicular cells from apoptosis by lead acetate, but higher doses could aggravate the testicular lesion.
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, DongHu Road 115, Wuhan 430071, P.R. China. chwang027@yahoo.com.cn
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Liang
authors.forename: Guang
authors.initials: G
authors.lastname: Shan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000633:toxicity*; D008297:Male; D051379:Mice; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013831:Thiamine / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007854:Lead; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D001205:Ascorbic Acid; D013831:Thiamine