Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hepatotoxicity of Two Progoitrin-Derived Nitriles in New Zealand White Rabbits

Version 1 : Received: 17 September 2020 / Approved: 18 September 2020 / Online: 18 September 2020 (10:07:03 CEST)

How to cite: Collett, M.G.; Matthews, Z.M.; Parton, K.H. Hepatotoxicity of Two Progoitrin-Derived Nitriles in New Zealand White Rabbits. Preprints 2020, 2020090427 (doi: 10.20944/preprints202009.0427.v1). Collett, M.G.; Matthews, Z.M.; Parton, K.H. Hepatotoxicity of Two Progoitrin-Derived Nitriles in New Zealand White Rabbits. Preprints 2020, 2020090427 (doi: 10.20944/preprints202009.0427.v1).

Abstract

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

Subject Areas

brassica-associated liver disease; BALD; progoitrin; 1-cyano-2-hydroxy-3-butene; 1-cyano-2-hydroxy-3,4-epithiobutane; nitrile; toxicity; rabbits

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