Excretion pattern and dynamics of glutathione detoxification of microcystins in Sprague Dawley rat

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.