Pyrrolizidine Alkaloid-Induced Depletion of Taurine from Rat Liver In Vivo and In Vitro
Pyrrolizidine alkaloids (PAs) are a group of plant hepatotoxins13,19. Certain PAs can also cause toxicity in extra-hepatic organs, including heart, lung, kidney and the CNS. PAs produce hepatotoxicity as a result of bioactivation to the corresponding dehydroalkaloids. Dehydroalkaloids are highly reactive molecules, with half-lives of a few seconds in water7. It has been suggested that alkylation of cell macromolecules by electrophilic dehydroalkaloids is the biochemical basis of toxicity7,25. Dehydroalkaloids can also conjugate with glutathione to form 7-glutathionyl-6,7-dihydroxymethyl-5H-pyrrolizine (GSDHP), a polar detoxification product released in high concentration into the bile20. Taurine has been shown to protect against toxic exposures in liver8,23, lung5,10,16,18,31–33 and heart2–4,9. We have reported that pretreatment with taurine reduced the cardiac toxicity of the PA, monocrotaline, in rats and reduced the LD50 from 80 mg/kg to 120 mg/kg40. In this study, we report the effect of PA exposures on hepatic taurine concentration in acute, subacute and pair-feeding studies in vivo, and perfused liver and liver slice incubations in vitro.
KeywordsLiver Slice Pyrrolizidine Alkaloid Taurine Level Taurine Concentration Taurine Content
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