The excretion route and dynamics of the glutathione (GSH) conjugate of microcystin-RR (MCRR), MCRR-GSH, were quantitatively studied in Sprague Dawley rat exposed with MCRR-GSH via liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the MCRR-GSH-treated rat, the average MCRR-Cysteine (MCRR-Cys)/MCRR-GSH ratio reached as high as 105.3, which indicated that the intermediate conjugate MCRR-GSH was rapidly converted to the product compound MCRR-Cys. Besides, MCRR was consistently detected in MCRR-GSH-treated rat, which suggested that MCRR can be dissociated from the MCRR-GSH conjugate and the reversibility of the MC-GSH conjugate. Results of total MC contents analysis in excrement showed that the total MC contents in urine were significantly higher than those in feces. The ratio of the total MC content in urine to feces was as high as 129.3, which demonstrates that the urine is the main route of excretion after MCRR-GSH-treatment. In urine, the MCRR-Cys concentration was 27.8-fold, 19.4-fold higher than MCRR-GSH and MCRR, respectively. Our results, for the first time, quantitatively found that MCRR-GSH was rapidly converted to MCRR-Cys after exposed to rat, and was excreted mainly through urine in the form of the MCRR-Cys conjugate. This study suggests that the GSH detoxification pathway of MCs could help to explain the greater sensitivity of mammals to MCs.

中文翻译：

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Sprague Dawley大鼠体内微囊藻毒素谷胱甘肽排毒的排泄模式和动力学

通过液相色谱电喷雾电离质谱法（LC-ESI-MS）定量研究了MCRR-GSH暴露的Sprague Dawley大鼠中微囊藻毒素-RR（MCRR）的谷胱甘肽（GSH）共轭物的排泄途径和动力学。 。在经MCRR-GSH处理的大鼠中，平均MCRR-半胱氨酸（MCRR-Cys）/ MCRR-GSH之比高达105.3，这表明中间缀合物MCRR-GSH迅速转化为产物化合物MCRR-Cys。此外，在MCRR-GSH处理的大鼠中始终检测到MCRR，这表明MCRR可以与MCRR-GSH结合物解离，并且MC-GSH结合物具有可逆性。粪便中总MC含量分析结果表明，尿液中总MC含量明显高于粪便中MC含量。尿液与粪便中总MC含量之比高达129.3，这表明尿液是MCRR-GSH处理后排泄的主要途径。尿液中的MCRR-Cys浓度分别比MCRR-GSH和MCRR高27.8倍，19.4倍。我们的结果首次定量地发现，MCRR-GSH暴露于大鼠后迅速转化为MCRR-Cys，并且主要通过尿液以MCRR-Cys缀合物的形式排泄。这项研究表明，MCs的GSH排毒途径可以帮助解释哺乳动物对MCs的更大敏感性。定量发现，MCRR-GSH暴露于大鼠后迅速转化为MCRR-Cys，并以MCRR-Cys缀合物的形式主要通过尿液排泄。这项研究表明，MCs的GSH排毒途径可以帮助解释哺乳动物对MCs的更大敏感性。定量发现，MCRR-GSH暴露于大鼠后迅速转化为MCRR-Cys，并以MCRR-Cys缀合物的形式主要通过尿液排泄。这项研究表明，MCs的GSH排毒途径可以帮助解释哺乳动物对MCs的更大敏感性。