Carcinogens pyrrolizidine alkaloids

Cynoglossum officinale (hound s tongue) contains alkaloids with curare-like activity as well as hepatotoxic and carcinogenic pyrrolizidine alkaloids, which are covered in a separate monograph. 

Mei, N., R.H. Heflich, M.W. Chou, and T. Chen. 2004. Mutations induced by the carcinogenic pyrrolizidine alkaloid riddelli-ine in the liver cII gene of transgenic Big Blue rats. Chem. Res. Toxicol. 17(6) 814-818. 

Some natural products, or their degradation products, represent a hazard for mammals not because of general toxicity but for subtle, adverse properties, such as carcinogenicity and tumor promotion. They are best known fi om marine dinoflagellates (okadaic acid and structural analogues), filamentous fungi (trichothecenes and ochratoxins), and plants (pyrrolizidine alkaloids). 

Comfrey is a perennial herb used for the prevention of kidney stones nourishing and repairing bone and muscle and for the treatment of injuries such as burns and bruises. In Australia, comfrey is classified as a poison and its sales have been restricted in several regions. Many different commercial forms of comfrey are marketed, including oral and external products. Commercial comfrey is usually derived from the leaves or roots of Symphytum officinale (common comfrey). However, some products are also derived from Russian comfrey. Russian comfrey contains a very toxic pyrrolizidine alkaloid, echimidine, which is not found in common comfrey. However, common comfrey contains other hepatotoxic alkaloids, namely 7-acetylintermedine, 7-acetyllycopsamine and symphytine. The metabolites of these alkaloids are very toxic to the liver. Ridker et al. documented hepatic venocclusive disease associated with consumption of comfrey root. Long-term smdies in animals have also confirmed the carcinogenicity of comfrey in animal models. ... 

Hirono I, Mori H, Yamada K, Hirata Y, Haga M, Takematsu H, Kanie S. Carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from Petasites japonicus Maxim. J Natl Cancer Inst 1977 58 1155-6. 

Apart from the chemistry of these pyrrolizidine alkaloids, their physiological effects, in particular their hepatotoxicity, have been investigated in depth by the CSIRO Division of Animal Health, as a result of which it has been possible to establish correlations between activity and structure liver damage is caused by alkaloids such as 90 or 91 because unsaturated amino alcohols of this type, which are esterified on one or both hydroxyl groups, undergo metabolism in the liver to form the toxin 93 this substance is immediately responsible for the mutagenic and carcinogenic effects observed [106, 107], which include... 

Israeli Arabs may be due to pyrrolizidine alkaloids. The carcinogenic activity of an alkaloidal extract from the phyto-... 

Chem. Soc. 74, 5612 (1952). Configuration Adams, Fles, ibid. 81, 5803 (1959) Robin. Crout, J. Chem. Soc. (C) 1969, 1386. Crystal structure H. Stoekli-Evans, Acta Crystallogr. B35, 231 (1979). Toxicology of monocrotaline and other pyrrolizidine alkaloids McLean, Pharmacol Rev. 22, 429-483 (1970) Allen et aL, Toxicol. Appl. Pharmacol. 23, 470 (1972) R. A. Roth ei al ibid. 60, 193 (1981). Review and evaluation of studies of carcinogenic and toxic action in laboratory animals JARC Monographs 10, 291-302, 333-342 (1976). Comprehensive reviews L. Bull et al. The... 

Carcinogenicity. The carcinogenicity of pyrrolizidine alkaloids has been debated since it was first reported, in part because of... 

Comfrey Symphytum officinale Anti-inflammatory gastritis diarrhea Hepatic veno-occlusive disease possible teratogen/carcinogen. (Note many other plants also contain hepatotoxic pyrrolizidine alkaloids-see Table 11-46). 

Wang, Y.P., J. Yan, P.P. Fu, and M.W. Chou. 2005. Human Uver microsomal reduchon of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid. Toxicol. Lett. 155(3) 411-420. 

Tussilagone and isotussilagone are pyrrolizidine alkaloids that have a saturated necine ring and are thus not toxic. Senkirkine and senecionine, however, have shown hepatotoxic and/or carcinogenic effects (Wichtl 2004). 

Hirono, I., H. Mori, and C.C.J. Culvenor. 1976. Carcinogenic activity of coltsfoot, Tussilago farfara L. Gann 67(1) 125-129. Kraus, C., G. Abel, and O. Schimmer. 1985. Studies on the chromosome damaging effect of some pyrrolizidine alkaloids in human lymphocytes in vitro. Planta Med. 51(2) 89-91. 

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