PMID- 21723383
OWN - NLM
STAT- MEDLINE
DCOM- 20111005
LR  - 20171116
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 205
IP  - 3
DP  - 2011 Sep 10
TI  - Photoirradiation of dehydropyrrolizidine alkaloids--formation of reactive oxygen 
      species and induction of lipid peroxidation.
PG  - 302-9
LID - 10.1016/j.toxlet.2011.06.020 [doi]
AB  - Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are 
      probably the most common poisonous plants affecting livestock, wildlife, and 
      human. PAs require metabolic activation to generate pyrrolic metabolites 
      (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and 
      genotoxicity, including tumorigenicity. In this study we report that UVA 
      photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, 
      dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, 
      dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 
      J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid 
      peroxidation in a light dose-responsive manner. When irradiated in the presence 
      of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation 
      was enhanced when methanol was replaced by deuterated methanol. These results 
      suggest that singlet oxygen is a photo-induced product. When irradiated in the 
      presence of superoxide dismutase, the level of lipid peroxidation decreased, 
      indicating that lipid peroxidation is also mediated by superoxide. Electron spin 
      resonance (ESR) spin trapping studies confirmed that both singlet oxygen and 
      superoxide anion radical were formed during photoirradiation. These results 
      indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen 
      species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation 
      of the parent PAs and other PA metabolites, including PA N-oxides, under similar 
      experimental conditions did not produce lipid peroxidation. It is known that PAs 
      induce skin cancer and are secondary (hepatogenous) photosensitization agents. 
      Our results suggest that dehydro-PAs are the active metabolites responsible for 
      skin cancer formation and PA-induced secondary photosensitization.
CI  - Published by Elsevier Ireland Ltd.
FAU - Zhao, Yuewei
AU  - Zhao Y
AD  - National Center for Toxicological Research, U.S. Food and Drug Administration, 
      Jefferson, AR 72079, USA.
FAU - Xia, Qingsu
AU  - Xia Q
FAU - Yin, Jun Jie
AU  - Yin JJ
FAU - Lin, Ge
AU  - Lin G
FAU - Fu, Peter P
AU  - Fu PP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20110622
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Carcinogens)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Linoleic Acids)
RN  - 0 (Lipid Peroxides)
RN  - 0 (Pyrrolizidine Alkaloids)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Solvents)
RN  - 11062-77-4 (Superoxides)
RN  - 11J6A3P924 (methyl linoleate hydroperoxide)
RN  - 17778-80-2 (Singlet Oxygen)
RN  - 24N6726DE5 (methyl linoleate)
RN  - 968JJ8C9DV (Sodium Azide)
RN  - AR09D82C7G (Deuterium)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - GAN16C9B8O (Glutathione)
RN  - Y4S76JWI15 (Methanol)
SB  - IM
MH  - Carcinogens/chemistry/*radiation effects/toxicity
MH  - Deuterium
MH  - Electron Spin Resonance Spectroscopy
MH  - Glutathione/analogs & derivatives/chemistry
MH  - Indicators and Reagents/chemistry
MH  - Kinetics
MH  - Linoleic Acids/chemistry/radiation effects
MH  - Lipid Peroxides/analysis/*chemistry
MH  - Methanol/chemistry
MH  - Pyrrolizidine Alkaloids/chemistry/*radiation effects/toxicity
MH  - Reactive Oxygen Species/*chemistry
MH  - Singlet Oxygen/chemistry
MH  - Sodium Azide/chemistry
MH  - Solvents/chemistry
MH  - Spin Trapping
MH  - Superoxide Dismutase/metabolism
MH  - Superoxides/chemistry/metabolism
MH  - Ultraviolet Rays
EDAT- 2011/07/05 06:00
MHDA- 2011/10/06 06:00
CRDT- 2011/07/05 06:00
PHST- 2011/03/02 00:00 [received]
PHST- 2011/06/14 00:00 [revised]
PHST- 2011/06/15 00:00 [accepted]
PHST- 2011/07/05 06:00 [entrez]
PHST- 2011/07/05 06:00 [pubmed]
PHST- 2011/10/06 06:00 [medline]
AID - S0378-4274(11)01287-2 [pii]
AID - 10.1016/j.toxlet.2011.06.020 [doi]
PST - ppublish
SO  - Toxicol Lett. 2011 Sep 10;205(3):302-9. doi: 10.1016/j.toxlet.2011.06.020. Epub 
      2011 Jun 22.