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).

中文翻译：

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二氢血红素碱在大鼠中的毒性和药代动力学：一项初步研究。

季苯并[c]菲啶生物碱血红碱碱（SG）是Sangrovit（一种天然牲畜饲料添加剂）的主要成分。二氢血根碱（DHSG）最近已被确定为大鼠的SG代谢产物。SG向DHSG的转化是SG在哺乳动物中可能的消除途径。进行这项研究以评估DHSG对90天饲料中100和500 ppm DHSG浓度的雄性Wistar大鼠的毒性（平均剂量为14和58 mg DHSG / kg体重/天）。与对照相比，在DHSG治疗的动物中，没有发现体重或器官重量的显着变化，器官的宏观细节，肝脏，回肠，肾脏，舌头，心脏或牙龈的组织病理学，血液中的临床化学或血液学标志物。通过Comet分析没有发现淋巴细胞DNA损伤，通过32P后标记在肝脏中形成DNA加合物，发现细胞色素P450 1A1 / 2的调节或氧化应激参数的变化。因此，与文献中公布的结果相比，在日粮中以高达500 ppm的剂量（即约58 mg / kg /天）重复服用DHSG达90天，没有发现毒性证据。同时，在口服剂量为9.1或91 mg / kg体重的大鼠中研究了DHSG的药代动力学。结果表明，DHSG在应用后的第一小时或第二小时经历了肠肝循环，血浆中浓度最大。DHSG相对较快地从体内清除（血浆水平分别在12或18小时后降至零）。与文献中公布的结果相比，约58 mg / kg /天）没有显示毒性证据。同时，在口服剂量为9.1或91 mg / kg体重的大鼠中研究了DHSG的药代动力学。结果表明，DHSG在应用后的第一小时或第二小时经历了肠肝循环，血浆中浓度最大。DHSG相对较快地从体内清除（血浆水平分别在12或18小时后降至零）。与文献中公布的结果相比，约58 mg / kg /天）没有显示毒性证据。同时，在口服剂量为9.1或91 mg / kg体重的大鼠中研究了DHSG的药代动力学。结果表明，DHSG在应用后的第一小时或第二小时经历了肠肝循环，血浆中浓度最大。DHSG相对较快地从体内清除（血浆水平分别在12或18小时后降至零）。