Previous evidence suggests that select nitrile and epithionitrile derivatives of glucosinolates can cause liver disease in cows grazing on brassica forage crops. A toxic incidence in New Zealand in cattle grazing brassica led us to investigate the direct in vitro hepatotoxicity and possible inhibition of the ABCG2 transporter of five nitrile compounds. In this study, we investigated 1-cyano-2-hydroxy-3-butene (CHB, epithionitrile derivative of progoitrin), 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB, nitrile derivative of progoitrin), 3-butenenitrile (nitrile from sinigrin), 4-pentenenitrile (nitrile from gluconapin), and 5-hexenenitrile (nitrile from glucobrassicanapin). Cell viability was assessed following 24- and 72-hr treatments with the 5 different compounds using the MTT assay (HepG2 cells and bovine primary liver cells). Additionally, ABCG2 transporter function was assessed. The results showed that none of the tested compounds caused cytotoxicity at concentrations up to 2 mM for 24hr. Over 72-hr the maximum concentration was 20 μM but no reduction in cell viability was observed. No inhibition of the ABCG2 transporter occured at concentrations up to 1 mM. Overall this study suggests that direct or secondary toxicity due to selected nitrile or epithionitrile derivatives of these glucosinolates was not the cause of the toxic event in cattle.
The in vitro toxicity of nitrile and epithionitrile derivatives of glucosinolates from rutabaga in human and bovine liver cells