The quaternary benzo[c]phenanthridine alkaloid sanguinarine (SG) is the main component of Sangrovit, a natural livestock feed additive. Dihydrosanguinarine (DHSG) has recently been identified as a SG metabolite in rat. The conversion of SG to DHSG is a likely elimination pathway of SG in mammals. This study was conducted to evaluate the toxicity of DHSG in male Wistar rats at concentrations of 100 and 500 ppm DHSG in feed for 90 days (average doses of 14 and 58 mg DHSG/kg body weight/day). No significant alterations in body or organ weights, macroscopic details of organs, histopathology of liver, ileum, kidneys, tongue, heart or gingiva, clinical chemistry or hematology markers in blood in the DHSG-treated animals were found compared to controls. No lymphocyte DNA damage by Comet assay, formation of DNA adducts in liver by 32P-postlabeling, modulation of cytochrome P450 1A1/2 or changes in oxidative stress parameters were found. Thus, repeated dosing of DHSG for 90 days at up to 500 ppm in the diet (i.e. approximately 58 mg/kg/day) showed no evidence of toxicity in contrast to results published in the literature. In parallel, DHSG pharmacokinetics was studied in rat after oral doses 9.1 or 91 mg/kg body weight. The results showed that DHSG undergoes enterohepatic cycling with maximum concentration in plasma at the first or second hour following application. DHSG is cleared from the body relatively quickly (its plasma levels drop to zero after 12 or 18 h, respectively).

• MeSH
• adukty DNA MeSH
• benzofenantridiny farmakokinetika   krev   toxicita   MeSH
• biochemická analýza krve MeSH
• časové faktory MeSH
• financování organizované MeSH
• ileum patologie   účinky léků   MeSH
• isochinoliny farmakokinetika   krev   toxicita   MeSH
• játra patologie   účinky léků   MeSH
• kometový test MeSH
• krmivo pro zvířata MeSH
• krysa rodu rattus MeSH
• náhodné rozdělení MeSH
• orgánová specificita MeSH
• oxidační stres účinky léků   MeSH
• pilotní projekty MeSH
• plocha pod křivkou MeSH
• poškození DNA účinky léků   MeSH
• potkani Wistar MeSH
• systém (enzymů) cytochromů P-450 účinky léků   MeSH
• testy genotoxicity MeSH
• tkáňová distribuce MeSH
• velikost orgánu účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH