Abstract
Ptaquiloside is a natural toxin present in bracken ferns (Pteridium sp.). Cattle ingesting bracken may develop bladder tumours and excrete genotoxins in meat and milk. However, the fate of ptaquiloside in cattle and the link between ptaquiloside and cattle carcinogenesis is unresolved. Here, we present the toxicokinetic profile of ptaquiloside in plasma and urine after intravenous administration of ptaquiloside and after oral administration of bracken. Administered intravenously ptaquiloside, revealed a volume of distribution of 1.3 L kg-1 with a mean residence-time of 4 hours. A large fraction of ptaquiloside was converted to non-toxic pterosin B in the blood stream. Both ptaquiloside and pterosin B were excreted in urine (up to 41% of the dose). Oral administration of ptaquiloside via bracken extract or dried ferns did not result in observations of ptaquiloside in body fluids, indicating deglycosolidation in the rumen. Pterosin B was detected in both plasma and urine after oral administration. Hence, transport of carcinogenic ptaquiloside metabolites over the rumen membrane is indicated. Pterosin B recovered from urine counted for 7% of the dose given intravenously. Heifers exposed to bracken for 7 days (2 mg ptaquiloside kg-1) developed preneoplastic lesions in the urinary bladder most likely caused by genotoxic ptaquiloside metabolites.
Highlights
Ptaquiloside (PTA) is the most well-studied member of the group of highly toxic and genotoxic illudane glucosides
Since the aqueous injection solution was prepared approximately 1 hour before administration, it was speculated if a fraction of PTA might have converted to pterosin B (PTB) before injection
Purified PTA was dissolved in sterile water immediately before administration in order to ensure that PTA was not hydrolysed to PTB before injection
Summary
Ptaquiloside (PTA) is the most well-studied member of the group of highly toxic and genotoxic illudane glucosides. The group comprises compounds like caudatoside, ptesculentoside, and ptaquiloside Z, all glycosides comprising a reactive cyclopropane ringsystem. PTA is present in many fern species, including the widespread bracken ferns (Fig 1; [1,2,3,4]). Ingestion of bracken by ruminants is associated with several diseases, including acute haemorrhagic disease (calves and sheep); bright blindness (sheep); bovine enzootic haematuria (cattle), and upper alimentary carcinoma (cattle) [5,6,7,8]. Bracken is the common name used for the 15 different Pteridium species of which P. aquilinum (L.) Kuhn is the most abundant taxa in Europe [1,9].
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