Porphyrogenic properties of the terpenes camphor, pinene, and thujone (with a note on historic implications for absinthe and the illness of Vincent van Gogh).
Camphor, alpha-pinene (the major component of turpentine), and thujone (a constituent in the liqueur called absinthe) produced an increase in porphyrin production in primary cultures of chick embryo liver cells. In the presence of desferrioxamine (an iron chelator which inhibits heme synthesis and thereby mimics the effect of the block associated with acute porphyria), the terpenes enhanced porphyrin accumulation 5- to 20-fold. They also induced synthesis of the rate-controlling enzyme for the pathway, 5-aminolevulinic acid synthase, which was monitored both spectrophotometrically and immunochemically. These effects are shared by well-known porphyrogenic chemicals such as phenobarbital and glutethimide. Camphor and glutethimide alone led to the accumulation of mostly uro- and heptacarboxylporphyrins, whereas alpha-pinene and thujone resulted in lesser accumulations of porphyrins which were predominantly copro- and protoporphyrins. In the presence of desferrioxamine, plus any of the three terpenes, the major product that accumulated was protoporphyrin. The present results indicate that the terpenes tested are porphyrogenic and hazardous to patients with underlying defects in hepatic heme synthesis. There are also implications for the illness of Vincent van Gogh and the once popular, but now banned liqueur, called absinthe.
Bonkovsky
H L
HL
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
Cable
E E
EE
Cable
J W
JW
Donohue
S E
SE
White
E C
EC
Greene
Y J
YJ
Lambrecht
R W
RW
Srivastava
K K
KK
Arnold
W N
WN
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis; D000434:Alcoholic Beverages / Q000266:history / Q000633:toxicity; D000818:Animals; D000081008:Bicyclic Monoterpenes; D002164:Camphor / Q000633:toxicity*; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005197:Famous Persons; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D049672:History, 19th Century; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D039821:Monoterpenes; D009426:Netherlands; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D010151:Paintings / Q000266:history; D011164:Porphyrias / Q000139:chemically induced / Q000266:history; D011166:Porphyrins / Q000378:metabolism; D013729:Terpenes / Q000266:history / Q000633:toxicity*
D000081008:Bicyclic Monoterpenes; D039821:Monoterpenes; D011166:Porphyrins; D013729:Terpenes; D002164:Camphor; C005790:beta-thujone; D003577:Cytochrome P-450 Enzyme System; C019781:benzphetamine N-demethylase; D006419:Heme Oxygenase (Decyclizing); D010089:Oxidoreductases, N-Demethylating; D000624:5-Aminolevulinate Synthetase; D003676:Deferoxamine; C005451:alpha-pinene