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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.

AbstractOBJECTIVE:
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.
CONCLUSION:
DIME has potentials for therapeutic use in amelioration of arsenic-induced reproductive toxicity.
AuthorsAsmita Samadder, Jayeeta Das, Sreemanti Das, Durba Das, Arnab De, Kakali Bhadra, Anisur Rahman Khuda-Bukhsh
JournalZhong xi yi jie he xue bao = Journal of Chinese integrative medicine (Zhong Xi Yi Jie He Xue Bao) Vol. 10 Issue 12 Pg. 1433-42 (Dec 2012) ISSN: 1672-1977 [Print] China
PMID23257138 (Publication Type: Journal Article)
Chemical References
  • Arsenites
  • Diterpenes, Kaurane
  • Plant Extracts
  • Sodium Compounds
  • dihydroxy-isosteviol-methyl-ester
  • sodium arsenite
  • Arsenic
Topics
  • Animals
  • Apoptosis (drug effects)
  • Arsenic (toxicity)
  • Arsenites (toxicity)
  • DNA Damage (drug effects)
  • Diterpenes, Kaurane (pharmacology)
  • Male
  • Mice
  • Plant Extracts (pharmacology)
  • Pulsatilla (chemistry)
  • Sodium Compounds (toxicity)
  • Spermatids (cytology, drug effects)

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