کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
11031868 1645770 2018 32 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Toxicological safety evaluation of 3,3′-diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Toxicological safety evaluation of 3,3′-diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine
چکیده انگلیسی
Diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine was evaluated for acute toxicity, mutagenic safety and metabolic stability. The estimated median oral lethal dose (LD50) cut-off of DSePA in mice and rat models was ∼200 mg/kg and ∼25 mg/kg respectively, which is considerably higher than the reported oral LD50 dose of its parent compound. Subsequently DSePA treatment in absence and presence of rat liver S9 fraction was found to be non-mutagenic at the tested doses up to 1 mM in rifampicin resistance assay and up to 6 mM in Ames test. In vitro degradation studies indicated that DSePA was more stable in S9 fraction of human compared to rat. The kinetic parameters Km and Vmax of DSePA degradation estimated using rat S9 fraction was 9.81 μM and 1.06 nmol/ml/min respectively. Further, DSePA treatment (1-50 μM) with or without rat S9 fraction did not induce any toxicity in human intestinal epithelial cells (Int 407) while showing comparable bioactivity of glutathione peroxidase (GPx) level. In conclusion, superior metabolic stability of DSePA in human S9 fraction with a concomitant lack of mutagenic effects suggests that it may be a suitable derivative of selenocytine for future biological studies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 99, November 2018, Pages 159-167
نویسندگان
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