Quantitatively evaluating detoxification of the hepatotoxic microcystins through the glutathione and cysteine pathway in the cyanobacteria-eating bighead carp.

Abstract

Glutathione (GSH) and cysteine (Cys) conjugation have long been recognized to be important in the detoxification of microcystins (MCs) in animal organs, however, studies quantitatively estimating this process are rare, especially those simultaneously determining multiple toxins and their metabolites. This paper, for the first time, simultaneously quantified MC-LR (leucine arginine), MC-RR (arginine arginine), MCLR-GSH/Cys and MCRR-GSH/Cys in the liver, kidney, intestine and muscle of the cyanobacteria-eating bighead carp i.p. injected with two doses of MCs using liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). MCLR-Cys and MCRR-Cys content were much higher in kidney than in liver, intestine and muscle, suggesting the organotropism to kidney, while MCLR-GSH and MCRR-GSH were always below the detection limit. Bighead carp effectively metabolized MC-LR and MC-RR into the cysteine conjugates in kidney, as the ratios of MCLR-Cys to MC-LR and MCRR-Cys to MC-RR reached as high as 9.04 and 19.10, respectively. MC-LR and MC-RR were excreted mostly in the form of MCLR/RR-Cys rather than MCLR/RR-GSH, while MCs-GSH might act as mid-metabolites and changed to the more stable MCs-Cys rapidly. Cysteine conjugation of MCs appears to be an important biochemical mechanism for the cyanobacteria-eating fish to resist toxic cyanobacteria. A comparison of such detoxification mechanisms between fish and mammals would be interesting in the future studies.