Lidocaine metabolites immunoactive? (Was: Re: Local anesthetic a carcinogen (Was: Re: Amalgam study))

Brian Sandle bsandle at southern.co.nz
Wed Oct 20 05:07:25 EST 1999


On sci.med.dentistry on Aug 14 1999
Brian Sandle <bsandle at southern.co.nz> wrote:
:Brian Sandle <bsandle at southern.co.nz> wrote:
:: Hans Lennros <hans.lennros at swipnet.se> wrote:
:: : Hi Joel,
:
:: : Do you do amalgams on expectant mothers?
:[...]
:: The aniline from the injection would probably be a lot worse.
:
:It is over 12 hours since I posted that and there has been no comment on 
:that point.
:
: 
:   Carcinogenesis 1994 Oct;15(10):2287-90
:   
:2,6-Dimethylaniline--hemoglobin adducts from lidocaine in humans.
: 
:    Bryant MS, Simmons HF, Harrell RE, Hinson JA
:    
:   Chemical Industry Institute of Toxicology, Research Triangle Park, NC
:   27709.
:   
:   Lidocaine (xylocaine) is utilized for the treatment of ventricular
:   arrhythmias which occur during cardiac surgery or myocardial
:   infarction and as a local anesthetic. Recent data from the National
:   Toxicology Program reported that a principal metabolite in man,
:   2,6-dimethylaniline, is carcinogenic in rats. In addition, the
:   putative metabolite N-hydroxy-2,6-dimethylaniline has been reported to
:   be mutagenic in Salmonella typhimurium TA100. N-Hydroxy metabolites of
:   aromatic amines may be oxidized by hemoglobin to the corresponding
:   nitroso metabolites and the nitroso may covalently bind to cysteine
:   groups in hemoglobin as the corresponding sulfinic acid amide. Since
:   hemoglobin binding is an indirect measure of the formation of the
:   N-hydroxy metabolite, we have examined the possibility that lidocaine
:   or a metabolite may similarly covalently bind to hemoglobin in rats
:   and humans. Using a previously developed gas chromatographic-mas
:   spectrometric assay, hemoglobin adducts of 2,6-dimethylaniline were
:   detected covalently bound to rat hemoglobin after administration of
:   either 2,6-dimethylaniline or lidocaine. Consistent with previously
:   reported observations, low levels of 2,6-dimethylaniline-hemoglobin
:   adducts were also observed in human subjects before lidocaine
:   administration. Following administration of lidocaine, all patients
:   had much higher levels of 2,6-dimethylaniline-hemoglobin adducts.
:   Differences in adduct levels in patients treated with lidocaine
:   (70-3760 mg) ranged from 93 to 636 ng/g hemoglobin. These data
:   indicate that N-hydroxy-2,6-dimethylaniline is a metabolite of
:   lidocaine in man.
:   
:   PMID: 7955068, UI: 95043037
:  
:[Medline is copyright]

Have to check the level of aniline metabolites and compare it to the 
amount in the toxic oil syndrome in Spain.

J Autoimmun 1995 Apr;8(2):293-303
 
Autoantibodies to cryptic epitopes of C-reactive protein and other acute
phase proteins in the toxic oil syndrome.
 
Bell SA, Du Clos TW, Khursigara G, Picazo JJ, Rubin RL
 
W.M. Keck Autoimmune Disease Center, Department of Molecular and
Experimental Medicine, Scripps Research Institute, La Jolla, California
92037, USA.
 
Toxic oil syndrome (TOS) was caused by the consumption of rapeseed oil
contaminated with derivatives of aniline. Many persons who survived the
acute phase developed a puzzling, multi-year chronic disease considered to
be inflammatory or autoimmune in nature. In attempting to characterize
their autoantibodies, we found that 74% of TOS patients with chronic
disease had IgG antibodies to C-reactive protein (CRP). This activity was
detectable only when CRP was chemically or physically denatured and behaved
like a previously described antibody produced by immunization with the CRP
monomer. Significant antibody reactivities to other acute phase proteins,
especially alpha 1-antitrypsin and fibrinogen (P < 0.025) and ceruloplasmin
(P < 0.05) were also observed. IgG antibodies to cryptic epitopes in CRP
and other major serum proteins that increase during the acute phase
response may reflect an earlier toxin-mediated insult to the liver that
included abnormal biosynthesis of and/or damage to acute phase proteins.
 
PMID: 7542004, UI: 95336602      





More information about the Toxicol mailing list