Pathological effects of dehydroheliotridine, a metabolite of heliotridine‐based pyrrol‐izidine alkaloids, in the young rat

Toxicity of pyrrolizidine alkaloids to humans and ruminants

“…3IX) which are more water-soluble and less reactive like the DHPAlks but still display a moderate level of alkylating activity (Peterson and Jago 1980;Robertson 1982). This higher watersolubility and lower reactivity can lead to escape from the liver tissue and subsequent reaction in other organs (Peterson et al 1972;IPCS 1989;Prakash et al 1999). It has been shown that a single exposure of DHPAlk can form macromolecular adducts that release DHNecs over a longer period which leads to on-going health problems (Peterson et al 1972;Prakash et al 1999).…”

“…This higher watersolubility and lower reactivity can lead to escape from the liver tissue and subsequent reaction in other organs (Peterson et al 1972;IPCS 1989;Prakash et al 1999). It has been shown that a single exposure of DHPAlk can form macromolecular adducts that release DHNecs over a longer period which leads to on-going health problems (Peterson et al 1972;Prakash et al 1999). DHNecs like dehydroretronecine and dehydroheliotridine have also been shown to produce rhabdomyosarcoma, skin, liver and lung tumours (Allen et al 1975;Shumaker et al 1976;Johnson et al 1978;Mattocks and Cabral 1982;Peterson and Culvenor 1983).…”

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

“…Pathologists have long before noticed karyomegalic cellular abnormalities in the liver and kidneys of animals who have been exposed to pyrrolizidine alkaloids with aflatoxin and busulphan. 3 Burry et al 4 reported the case of a 22-year-old female whose autopsy revealed megalocytosis and extreme dysplasia in the liver, kidney, and pancreas, without any history of exposure to toxins. Mihatsch et al 5 conducted the first study, which described these megalocytic changes and associated interstitial inflammation, a unique entity-karyomegalic interstitial nephritis.…”

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

“…The reactivity of DHPAs interacting with DNA is based on the evidence obtained from both in vivo and in vitro studies, while the DNA reactivity of second-ary PA metabolites is based on the evidence obtained from in vitro studies. CYS denotes the conjugated cysteine group, GS denotes the conjugated glutathione group, and dR denotes deoxyribose and more unidentified, are much more persistent and may possibly cause PDA formation and resultant genotoxicity in prolonged periods (Peterson et al 1972;Prakash et al 1999).…”