title: Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: its toxicity, drug-DNA interaction and signaling cascades.
abstract: OBJECTIVE
  To evaluate the ameliorative efficacy of dihydroxy-isosteviol methyl ester (DIME) of Pulsatilla nigricans extract in arsenic-induced DNA damage in testis cells of mice.
  
  
  METHODS
  The mice were treated with sodium arsenite (SA) solution intragastrically at a dose of 20 mg/kg per day and examined at 30, 60, and 90 d after treatment. We divided SA-intoxicated mice into two sub-groups: one fed with DIME at a dose of 35 mg/kg and the other with 85% alcohol. We analyzed the expressions of apoptotic signal proteins like CYP1A1, p53 and caspase 3, ascertained the level of cellular and DNA damage and estimated the level of testicular-toxicity biomarkers. We studied the interaction of DIME with calf thymus DNA as target through circular dichroism spectra and melting temperature profiles.
  
  
  RESULTS
  We observed an elevation in all apoptotic and toxicity biomarkers leading to cellular and DNA damage in the SA-intoxicated mice which showed significant inhibition or reversal on administration of DIME. Results also showed that DIME interacted with DNA, bringing in discernible changes in structure and conformation.
  
  
  CONCLUSIONS
  DIME has potentials for therapeutic use in amelioration of arsenic-induced reproductive toxicity.
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
authors.forename: Asmita
authors.initials: A
authors.lastname: Samadder
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Das
authors.forename: Sreemanti
authors.initials: S
authors.lastname: Das
authors.forename: Durba
authors.initials: D
authors.lastname: Das
authors.forename: Arnab
authors.initials: A
authors.lastname: De
authors.forename: Kakali
authors.initials: K
authors.lastname: Bhadra
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity; D018053:Arsenites / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D031946:Pulsatilla / Q000737:chemistry*; D017670:Sodium Compounds / Q000633:toxicity; D013087:Spermatids / Q000166:cytology / Q000187:drug effects*
chemical_list: D018053:Arsenites; D045786:Diterpenes, Kaurane; D010936:Plant Extracts; D017670:Sodium Compounds; C579618:dihydroxy-isosteviol-methyl-ester; C017947:sodium arsenite; D001151:Arsenic