Camphor: Benefits and risks of a widely used natural product

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Abstract
The main aspects of the non-clinical profile of D-camphor, a natural product widely used as a common remedy for several symptoms, are reviewed. The pharmacodynamics and toxicity of this substance are analyzed, with regard to all the literature available, in order to assess a risk profile and better understand the positive and negative results connected with its use. The general conclusion is that the main risks of camphor as a medicinal product are mainly due to a somehow diffused attitude of considering it as "not a real medicine", and to its consequent sometimes not sufficiently careful administration.
Volume 53(2):77-82, 2009
Acta Biologica Szegediensis
http://www.sci.u-szeged.hu/ABS
REVIEW
1Department of Crop Biology, Sect. Plant Physiology, University of Pisa, Pisa, Italy, 2Department of Veterinary Clinics,
University of Pisa, Pisa, Italy
Camphor: benefits and risks of a widely used natural
product
Paolo Zuccarini1*, Giulio Soldani2
ABSTRACT
The main aspects of the non-clinical profile of D-camphor, a natural product
widely used as a common remedy for several symptoms, are reviewed. The pharmacodynamics
and toxicity of this substance are analyzed, with regard to all the literature available, in order
to assess a risk profile and better understand the positive and negative results connected with
its use. The general conclusion is that the main risks of camphor as a medicinal product are
mainly due to a somehow diffused attitude of considering it as “not a real medicine”, and to
its consequent sometimes not sufficiently careful administration.
Acta Biol Szeged 53(2):77-82 (2009)
KEY WORDS
D-camphor
pharmacodynamic
pharmacokinetics
risk/benefit assessment
toxicity
Accepted Oct 20, 2009
*Corresponding author. E-mail: p.zuccarini@virgilio.it
77
Camphor (Figure 1) is a natural product deriving from the
wood of the camphor laurel (Cinnamomum camphora L.)
trees through steam distillation and puriÞcation by sublimi-
nation; the trees used should be at least 50 years old. It also
occurs in some other related trees in the laurel family, notably
Ocotea usambarensis Eng., and can also be obtained from
the plant Lippia dulcis Trev., but this is not a major industrial
source (Compadre et al. 1986). A major source of camphor in
Asia is Ocimum kilimandscharicum Baker ex Gurke.
Camphor can also be produced synthetically from vinyl
chloride and cyclopentadiene, passing through the intermedi-
ate dehydronorbornyl chloride. The naturally occurring form
is dextrorotatory and the synthetic form optically inactive
(Budavari 1989; Reynolds 1989).
Camphor has a counterirritant, rubefacient and mild
analgesic action, and is a major component of liniments for
relief of Þbrositis, neuralgia and similar conditions. It can be
used as a mild expectorant; if ingested, camphor has irritant
and carminative properties. Camphorated-oil, a solution in
oil given through intramuscular or subcutaneous way, can be
used as a circulatory and respiratory stimulant, but this use is
considered hazardous. When, in combination with menthol
and chenodeoxycholic acid, it has been used to aid dispersal
of bile duct stones, although this is no longer recommended
(Reynolds 1989).
Aim of the present work is to provide an overview over
pharmacological and toxicological aspects of camphor, in
order to assess its safety proÞle and evaluate the level of risk
connected with its use.
Pharmacology
Pharmacodynamics
Camphor, a natural product derived from the wood of the tree
Cinnamomum camphora, has a long history of use as anti-
septic, analgesic, antipruritic, counterirritant and rubefacient
(Hercogov 2005; Lynde et al. 2008). Its success and wide
medical use, especially in topical preparations, is connected
to its mild local anesthesizing effect and to the production
of a circumscribed sensation of heat, together with its char-
acteristic and penetrating odour that is by most of people
associated to the idea of a strong and effective medicine
(Gibson et al. 1989).
Camphor is today mostly used in the form of inhalants and
of camphorated oil, a preparation of 19% or 20% camphor
in a carrier oil, for the home treatment of colds (Jochen and
Theis 1995) and as a major active ingredient of liniments and
balms used as topical analgesics (Xu et al. 2005).
The antitussive, nasal decongestant and expectorant action
of camphor and of its derivatives was one of the Þrst ones to
be systematically investigated (Inoue and Takeuchi 1969).
Its nasal decongesting activity seems to be not purely me-
chanic, but connected with the stimulation of cold receptors
in the nose. The inhalation of camphor vapours (so as the one
of eucalyptus and menthol vapours) on a sample of volunteers
increased the nasal sensation of airßow through the induction
of cold sensation in the nose, despite of actually not affecting
nasal resistance to airßow (Burrow et al. 1983).
More recent studies pointed out how camphor efÞcacy
in the treatment of cold is due to its antispasmodic action
(Astudillo et al. 2004), and how the effects of camphor on
bronchospasm are connected to its anti-histaminergic and
anti-cholinergic activities (Grnemann et al. 2008). In fact,
78
Zuccarini, Soldani
camphor appears to be effective to reduce histamine H1 and
muscarinic M3 receptor-mediated bronchocostriction (Grne-
mann et al. 2008), and this action relates also to the inhibition
of cough (Kreutner et al. 2000).
Camphor was administered in the form of aromatic vapor,
at the concentrations of 50, 133 and 500 µg l-1, to guinea pigs
subject to chemically induced cough. No effect were regis-
tered at the lowest concentrations, but 500 µg l-1 camphor gave
a 33% reduction of cough frequency, to which an increase in
cough latency coincided (Laude et al. 1994).
The analgesic proprieties of camphor are largely known
and applied, but little is known about the molecular mecha-
nisms that are at their basis. (Xu et al. 2005).
Moqrich et al. (2005) demonstrated that camphor activates
TRPV3, a member of transient receptor channel superfamily,
leading to excitation and desensitization of sensory nerves.
The notorious effect of generation of a sensation of heath
associated with topic application of camphor (Green 1990)
is a consequence of this activation. In fact, TRPV3 is a warm-
sensitive Ca2+-permeable cation channel, that once activated
originates the warm sensation, actually simulating an effective
increase of temperature in the treated area (Xu et al. 2006).
This effect, caused by an increase in intracellular Ca2+ lev-
els, is typical also of other natural compounds as carvacrol,
eugenol and thymol (Xu et al. 2006).
Anyway excessive and repeated application of camphor
can lead to sensibilization of TRPV3, in apparent contrast
with its analgesic role (Peier et al. 2002; Moqrich et al.
2005).
The antipruritic and counterirritant activity of camphor
is instead associated with its capacity of activating TRPV1
- another member of TRP channel superfamily - at the level
of dorsal root gangliar [DRG] neurons and inhibiting TRPA1
channels (Moqrich et al. 2005; Nagata et al. 2005), action
that is in common with other TRPV1 agonists (Bhave et al.
2002; Xu et al. 2006; Belmonte and Viana 2008). The recently
clariÞed activity of camphor as a TRPA1 inhibitor has been
utilized by Lee et al. (2008) for pretreatment of human em-
bryonic kidney cells tested for membrane potential changes
elicited by thymol, showing how the response to thymol is
blocked by camphor. Bang et al. (2007) showed camphor
to suppress acute pain in mouse consequent to intradermal
administration of acetaldehyde into mouse footpads.
Capsaicin shares the same action with camphor, but per-
forms it more slowly and less completely; on the other side
camphor efÞcacy is lower, since higher concentrations are
required (Xu et al. 2005). Studies on rats demonstrated that
the actions of capsaicin and camphor are segregated (Wu et
al. 2005), i.e. they are mediated by distinct channel regions,
and camphor did not activate TRPV1 in capsaicin-insensitive
chickens (Xu et al. 2005; Jordt and Julius 2002).
Camphor also inhibits other related TRP channels such as
ankyrin-repeat TRP1 (TRPA1), which is a further evidence
underlying its analgesic effects (Xu et al. 2005).
Camphor was shown to inhibit mitochondrial respiration.
Administration of up to 8 µM of camphor inhibited respira-
tion rate in rat-liver mitochondria, nearly halving the oxygen
consumption; this suggests that camphor may be used in oxy-
genating tumors prior to radiotherapy (Guilland-Cumming
and Smith 1979; 1982).
Camphor can also be a potential radiosensitizing agent
in radiotherapy. Treatment with camphor (0.5 µmol á body
wt-1) 45 minutes before local x-irradiation at the dose levels
of 30, 80, 100 or 120 Gy was performed on male C3H/Jax
mice bearing transplanted mammary tumours. Sequential
measurement of the tumour volumes during 45 days after the
irradiation revealed a 4.8 delay of the maximum enhancement
ratios in tumour growth (Goel and Roa 1988).
D-camphor (1100 µg ml-1) inhibited oxidative metabolism
in E.coli (Cardullo and Gilroy 1975). Succinic, lactic and
NADH-oxidase activities were inhibited, while NADH and
succinic DCPIP oxidoreductase enzymes were unaffected.
The restoration of succinic oxidase activity by ubiquinone
(Q6) but not by vitamin K1 indicates that D-camphor may
operate this inhibition by affecting quinone functions.
Pharmacokinetics
Camphor is readily absorbed from all the sites of administra-
tion, after inhalation, ingestion or dermal exposure (Baselt
and Cravey 1990). Peak plasma levels were reached by 3
hours post-ingestion when 200 mg camphor was taken alone,
and 1 hour post-ingestion when it was ingested with a solvent
(Tween 80; Koppel et al. 1988).
In case of dermal application, the volume of the absorp-
tion is relatively low in comparison with the speed of the
process. After application of different numbers of commercial
patches [2, 4 or 8] to the skin of human subjects during 8
hours, the levels of camphor in the plasma were assayed with
selective gas-cromatography (Valdez et al. 1999; Martin et
Figure 1. Structural formula of Camphor, a bicyclic monoterpene ketone
(1,7,7-trimethylbicyclo [2.2.1] heptan).
79
Camphor: its beneÞts and risks
al. 2004). Maximum camphor plasma concentration resulted
in a range between 35.2 and 46.8 ng/ml-1 in the case of 8
patches, between 19.6 and 34 ng/ml-1 for the 4 patches while
almost undetectable concentrations were observed when only
2 patches had been applied, showing that dermal absorption
is prompt but not massive.
Camphor is distributed throughout the whole body, and
can permeate the placenta; for this reason it must be recom-
mended that the use of this product is avoided during preg-
nancy and lactation (Sweetman 2005).
Its volume of distribution is 2-4 L/kg (Koppel et al. 1988);
plasma protein binding has been estimated as 61% (Koppel
et al. 1982).
After its absorption and distribution, camphor undergoes
hepatic metabolism: it is hydroxylated in the liver into hy-
droxycamphor metabolites (Sweetman 2005).
Asahina and Ishidate (1933; 1934; 1935) isolated cis-
and trans-¹-hydroxycamphor and camphor-¹-carboxylic
acid from the urine of dogs that had been fed with camphor;
Shimamoto (1934) obtained 3-hydroxycamphor (15%),
5-hydroxycamphor (55%) and trans-¹-hydroxycamphor
(20%) from the urine of dogs, and 5-hydroxycamphor [as
major metabolite] and 3-hydroxycamphor from the urine of
rabbits.
Robertson and Hussain (1969) observed that (+)-cam-
phor and (-)-camphor increase the content of glucuronide
in the urine of rabbits; (+)-camphor was moreover reduced
to (+)-borneol as well as being hydroxylated to (+)-5-endo-
hydroxycamphor [major product] and (+)-3-endo-hydroxyc-
amphor.
Hydroxylation of camphor, as well as norcamphor, peri-
cyclocamphanone and 5,5-dißuorocamphor, is mainly per-
formed by cytochrome P450 (Collins and Loew 1988), a class
of heme-containing monooxygenases that are distributed in
the whole body (Boxenbaum 1984), by hydrogen abstraction
(Wand and Thompson 1986). Cytochrome P450 is responsible
for camphor conversion into 5-hydroxycamphor (Gelb et al.
1982), while 3-hydroxycamphor is the primary product of
non-enzymatic hydroxylation of camphor (Land and Swallow
1979). Camphor hydroxylation by cytochrome P450 occurs
with a different region-speciÞcity for camphor and its related
compounds (Collins and Loew 1988).
Hydroxylated metabolites are then conjugated with
glucuronic acid and excreted in the urine (Sweetman 2005).
The half-life of 200 mg of camphor was 167 minutes when
ingested alone, and 93 minutes when ingested with a solvent
(Tween 80) (Koppel et al. 1988).
Camphor can modulate the activities of hepatic enzymes
involved in phase I and phase II drug metabolism. 50, 150
and 300 mg/Kg-1 of camphor dissolved in 0.1 ml of olive oil
was administered daily to female Swiss Albino mice during
20 days. At its highest concentration it caused a signiÞcant
increase in the activities of cytochrome P450, cytochrome b5,
aryl-hydrocarbon hydroxylase and glutathione S-transferase,
signiÞcantly elevating the level of reduced glutathione in the
liver (Banerjee et al. 1995).
Interactions
Very few studies of pharmacological interactions between
camphor and other compounds are present in literature. In a
study combining the administration of D-camphor and an ex-
tract from fresh crataegus berries, a synergic action of the two
preparations emerged in ameliorating cardiac performances.
Both D-camphor and the extract contributed in an increase
in total peripheral resistance induced by an increase tone of
the arterioles, and while the former appeared to be the main
factor in inducing the rapid initial effect, the former added a
long-lasting effect (Belz and Loew 2003).
Toxicity
Camphor occurs in nature in its dextrorotatory form (D-
camphor), while the laevorotatory form (L-camphor) exists
only as a synthetic form. The two enantiomers present dif-
ferent proÞles of toxicity.
D-camphor, L-camphor and their racemic mixture were
tested for toxicity in mice. At 100 mg á Kg b.w.-1 the natural
form was non toxic, while the synthetic form induced differ-
ent kinds of toxic and behavioural effects such as body jerks
and hunched posture; the racemic mixture showed similar
effects to the L-form (Chatterjie and Alexander 1986).
The oral administration of acute doses of D-camphor to
rats and rabbits caused pronounced signs of toxicity. In rats,
the consume of food was reduced proportionally to the ad-
ministered dose, starting from 464 mg á Kg b.w.-1 á day-1, and
at 1000 mg á Kg b.w.-1 á day-1 convulsions and pilo-erection
were observed, connected with a reduction of motility and
weight gain. Reduced body weight gain and food consump-
tion were observed in rabbits treated with 681 mg á Kg b.w.-1
á day-1 (Leuschner 1997).
Camphor showed porphyrogenic activity in primary cul-
tures of chick embryo - liver cells, with enhanced porphyrin
accumulation ranging from 5- to 20-fold (Bonkovsky et al.
1992).
The main problems about camphor toxicity in humans
are connected more to the large availability of camphor-
containing products and their diffused perception as un-
hazardous medicines rather than in the intrinsic toxicity of
camphor. The daily maximum human therapeutic dose is in
fact approximately 1.43 mg á Kg-1, which corresponds to a
therapeutic ratio of more than 450 for the endpoint toxicity,
reßecting a wide margin of safety (Leuschner 1997). On the
other side, as mentioned above, camphor is present in several
over-the-counter products, its use as a familiar remedy is com-
monly accepted, but still some lack of information persists
among the consumers.
80
Zuccarini, Soldani
Cases of camphor intoxication in humans, especially
children, are relatively frequent, mostly because of accidental
ingestion (Siegel and Wason 1986). More than 100000 cases
of ingestion exposures to camphor-containing products were
registered between 1990 and 2003 (Manoguerra et al. 2006),
causing a range of symptoms that comprises convulsion,
lethargy, ataxia, severe nausea, vomiting and coma (Koppel
et al. 1988; Manoguerra et al. 2006).
Reproduction toxicity
D-camphor was orally administered to pregnant rats and
rabbits during the period of organogenesis to test its embryo-
toxicity. Doses up to 1000 mg á Kg b.w.-1 á day-1 to rats and up
to 681 mg á Kg b.w.-1 á day-1 to rabbits showed no teratogenic
effects, and in none of the animals were observed higher rates
of mutations or malformations (Leuschner 1997).
Mutagenicity and cancerogenicity
In a Salmonella/microsome assay, the upper limit of the dose
interval tested for (+/-) camphor resulted to be the highest
non-toxic dose, suggesting that the compound is not muta-
genic in the Ames test (Gomes-Carneiro et al. 1998).
A single dose of camphor (0.5 µM á g-1) administered 30,
45 or 60 minutes before gamma irradiation signiÞcantly re-
duced the frequency of sister-chromatid exchanges in mouse
bone marrow, showing therefore a radiomodifying inßuence
(Goel at al. 1989).
Discussion and Conclusions
Camphor is familiar to many people as a principal ingredient
in topical home remedies for a wide range of symptoms, and
its use is well consolidated among the population of the whole
world, having a long tradition of use as antiseptic, antipruritic,
rubefacient, abortifacient, aphrodisiac, contraceptive and
lactation suppressant.
In particular, the analgesic and antipruritic action of
the compound make it appreciated by a large number of
consumers, by whom it is used in the form of essential oil
for cutaneous application. Itch is a complex phenomenon,
being difÞcult to localize and quantify (Wahlgren 1995) and
involving a variety of skin surface receptors, peripheral and
central nerves and speciÞc brain regions. The treatment of
itch usually relies on antisthamines, corticoids or various
topical remedies (Langner and Maibach 2009) among which
camphor has a prominent role. The analgesic action is due to
its interacions with members of TRP channel superfamily
Camphor is therefore an important remedy for symptom-
atic treatment of itching, especially in patients affected by
contact dermatitis, because it goes to affect directly the cuta-
neous nerve ending, as other agents like pramoxine, phenol
and menthol do (Burkhart and Burkhart 2003).
Camphor has also an important role in the treatment of
cough and colds thanks to its antispasmodic activity, due to
anti-histaminergic and anti-cholinergic action that causes
depression of bronchospasm coupled with inhibition of
cough.
This compound has also a long history of scientiÞc studies
on its action and on the way through which it is metabolized
in the organisms of both humans and animals, due to the
general interest that it has always arisen among common
people and scientists. Already in 1879, Schmeideberg and
Meyer were analyzing the metabolites isolated from the urine
of dogs that had been fed with (+/-) camphor (Schmiedeberg
and Meyer 1879), and during the Þrst half of the twentieth
century the number of studies focused on its pharmacology
and pharmacokinetics has been remarkable.
The bibliographic search that was performed for the com-
pilation of this toxico-pharmacological overview revealed a
rich literature existing on camphor, and put in evidence the
large amount of works focused on toxic aspects of camphor
that were published during the last 30 years; a great number
of reports concerning cases of camphor intoxication were also
collected. In most cases camphor intoxication occurred fol-
lowing accidental ingestion of camphor-containing product,
and sometimes lethal episodes of intoxication of infants due
to application of camphor to their nostrils were collected.
As it emerges from all the observed data the toxic risks of
camphor-containing products in general, and of camphorated
oil in particular, are connected essentially with its improper
uses, e.g. accidental ingestion, but camphor does not repre-
sent a threaten for safety when used on the target patients,
following the indicated dosages and the contraindications.
Special care must be taken during pregnancy, due to the fact
that camphor crosses the placental barrier, and camphor and
camphor containing products should be avoided in children
who have a history of febrile convulsions or other predispos-
ing factors for convulsions (Galland et al. 1992).
In the past, when camphor was used medicinally, the
oral doses ranged from 120-300 mg (Wade 1977), and the
parenteral dose range was from 60-200 mg (not recommended
anymore).
Camphorated oil can be used with no risks for safety when
following the prescriptions. The relatively diffused tendency
to the improper use of camphor (high dosages, accidental
ingestion, use on infants) is connected with the perception
of the product, by many consumers, as a sort of ÒpanaceaÓ
with no contraindication. More and more accessible informa-
tion is therefore necessary to bring to a ÒresponsabilizationÓ
of the consume of this product, in order to avoid hazardous
situations.
All the above considerations allow the conclusion that
camphor in its form of camphorated oil can be safely used
at the proposed dosages, on the indicated patients target, for
topic application.
81
Camphor: its beneÞts and risks
Acknowledgements
The Authors would like to thank Annie Hart (A.R.S.) and
Marina Ribatski (B.D.R.) for useful help during the elabora-
tion of the manuscript.
References
Asahina Y, Ishidate M (1933) Ber dtsch chem Ges 67:71.
Asahina Y, Ishidate M (1934) Ber. dtsch. chem. Ges 68B:967.
Asahina Y, Ishidate M (1935) Ber dtsch chem Ges 69:349.
Astudillo A, Hong E, Bye R, Navaretta A (2004) Antispasmodic activity of
Acalypha phleoides Cav. Phytother Res 18:102-106.
Banerjee S, Welsch CW, Rao AR (1995) Modulatory inßuence of camphor
on the activities of hepatic carcinogen metabolizing enzymes and the
levels of hepatic and extrahepatic reduced glutathione in mice. Cancer
Letters 88(2):163-169.
Bang S, Kim KY, Yoo S, Kim YG, Hwang SW (2007) Transient receptor
potential A1 mediates acetaldehyde-evoked pain sensation. European
Journal of Neurosciences 26:2516-2523.
Baselt RC, Cravey RH (1990) Disposition of toxic drugs and chemicals and
drugs 3rd ed. Year Book Medical Publishers Inc.
Belmonte C, Viana F (2008) Molecular and cellular limits to somatosensory
speciÞcity. Mol Pain 4:14-31.
Belz GG, Loew D (2003) Dose-response related efÞcacy in orthostatic
hypotension of a Þxed combination of D-camphor and an extract from
fresh crataegus berries and the contribution of the single components.
Phytomedicine 4:61-67.
Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW (2002)
cAMP-dependent protein kinase regulates desensitization of the capsai-
cin receptor (VR1) by direct phosphorylation. Neuron 35(4):721-731.
Bonkovsky HL, Cable EE, Cable JW, Donohue SE, White EC, Greene YJ,
Lambrecht RW, Srivastava KK, Arnold WN (1992) Porphyrogenic
properties of the terpenes camphor, pinene, and thujone (with a note on
historic implications for absinthe and the illness of Vincent van Gogh).
Biochem Pharmacol 43(11):2359-2368.
Boxenbaum H (1984) Interspecies Pharmacokinetic Scaling and the Evolu-
tionary-Comparative Paradigm. Drug Metab Rev 15:1071-1121.
Budavari S (Ed.), (1989) The Merck Index. 11th Edition. Merck and Co
Inc, Rahway, USA.
Burkhart CG, Burkhart HR (2003) Contact irritant dermatitis and anti-pruritic
agents: the need to address the itch. J Drugs Dermatol 2(2):143-146.
Burrow A, Eccles R, Jones AS (1983) The effects of camphor, eucalyptus
and menthol vapour on nasal resistance to airßow and nasal sensation.
Acta Otolaryngologica 96(1-2):157-161.
Cardullo MA, Gilroy JJ (1975) Inhibition of oxidative metabolism in Escheri-
chia coli by d-camphor and restoration of oxidase activity by quinones.
Can J Microbiol 21(9):1357-1361.
Chatterjie N, Alexander GJ (1986) Anticonvulsant properties of spirohy-
dantoins derived from optical isomers of camphor. Neurochem Res
11(12):1669-1676.
Collins JR, Loew GH (1988) Theoretical study of the product speciÞcity
in the hydroxylation of camphor, norcamphor, 5,5-dißuorocamphor,
and pericyclocamphanone by cytochrome P450cam. J Biol Chem
263(7):3164-3170.
Compadre CM, Robbins EF, Kinghorn AD (1986) The intensely sweet herb,
Lippia dulcis Trev.: historical uses, Þeld enquiries, and constituents. J
Ethnopharmacol 15(1):89-106.
Galland MC, Griguer Y, Morange-Sala S, Jean-Pastor MJ, Rodor F, Jouglard
J (1992) Convulsions febriles: faut-il contre-indiquer certains medica-
ments? Therapie 47(5):409-414.
Gelb MH, Heimbrook DC, Miilkonen P, Sligar SG (1982) Stereochemistry
and deuterium isotope effects in camphor hydroxylation by the cyto-
chrome P450cam monooxygenase system. Biochemistry 21(2):370-
377.
Gibson DE, Moore GP, Pfaff JA (1989) Camphor ingestion. Am J Emerg
Med 7:41-43.
Goel HC, Roa AR (1988) Radiosensitizing effect of camphor on transplant-
able mammary adenocarcinoma in mice. Cancer Lett 43(1-2):21-27.
Goel HC, Singh S, Singh SP (1989) Radiomodifying inßuence of camphor
on sister-chromatid exchange induction in mouse bone marrow. Mutat
Res 224(2):157-160.
Grnemann T, Nayal R, Peretz HH, Melzig MF (2008) Antispasmodic
activity of essential oil from Lippia dulcis Trev. J Ethnopharmacol
117:166-169.
Green BG (1990) Sensory characteristics of camphor. J Invest Dermatol
94(5):662-666.
Gomes-Carneiro MR, Felzenszwalb I, Paumgartten FJ (1998) Mutagenicity
testing (+/-)-camphor, 1,8-cineole, citral, citronellal, (-)-menthol and
terpineol with the Salmonella/microsome assay. Mutat Res 416(1-2):
129-136.
Guilland-Cumming D, Smith GJ (1979) Mitochondrial respiration depressed
by camphor: a possible aid in radiotherapy. Experientia 35(5):659.
Guilland-Cumming DF, Smith GJ (1982) The effect of camphor on mito-
chondrial respiration. Experientia 38(2):236-237.
Hercogov J (2005) Topical anti-itch therapy. Dermatol Ther 18:341-343.
Inoue Y, Takeuchi S (1969) Expectorant-like action of camphor derivatives.
Nippon Ika Daigaku Zasshi 36(4):351-354.
Land EJ, Swallow AJ (1979) Some free radical reactions of camphor in rela-
tion to the action of cytochrome P450. Journal of the Chemical Society,
Faraday Transactions I 75:1849-1856.
Langner MD, Maibach HI (2009) Pruritus measurement and treatment. Clin
Exp Dermatol 34:285-288.
Laude EA, Morice AH, Grattan TJ (1994) The antitussive effects of men-
thol, camphor and cineole in conscious guinea-pigs. Pulm Pharmacol
7(3):179-184.
Lee SP, Buber MT, Yang Q, Cerne R, Corts RY, Sprous DG, Bryant RW
(2008) Thymol and related alkyl phenols activate the hTRPA1 channel.
Br J Pharmacol 153:1739-1749.
Leuschner J (1997) Reproductive toxicity studies of D-camphor in rats and
rabbits. Arzneimittelforschung 47(2):124-128.
Jochen GW, Theis MD (1995) Camphorated oil: still endangering the lives
of Canadian children. Can Med Assoc J 152(11):1821-1824.
Jordt SE, Julius D (2002) Molecular basis for species-speciÞc sensitivity to
ÒhotÓ chili peppers. Cell 108(3):421-430.
Koppel C, Tenczer J, Schirop T, Ibe K (1982) Camphor poisoning - abuse of
camphor as a stimulant. Arch Toxicol 51:101-106.
Koppel C, Martens F, Schirop Th, Ibe K (1988) Hemoperfusion in acute
camphor poisoning. Intensive Care Medicine 14:431-433.
Kreutner W, Hey JA, Anthes J, Barnett A, Young S, Tozzi A (2000) Preclinical
pharmacology of desloratadine, a selective and nonsedating histamine
H1 receptor antagonist. Arzneimittel forschung 50:345-352.
Lynde CB, Kraft JN, Lynde CW (2008) Novel agents for intractable itch.
Skin Therapy Letters 13(1):6-9.
Manoguerra AS, Erdman AR, Wax PM, Nelson LS, Caravati EM, Cobaugh
DJ, Chyka PA, Olson KR, Booze LL, Woolf AD, Keyes DC, Christian-
son G, Scharman EJ, Troutman WG (2006) Camphor Poisoning: an
evidence-based practice guideline for out-of-hospital management. Clin
Toxicol (Phila) 44(4):357-370.
Martin D, Valdez JS, Boren J, Mayersohn M (2004) Dermal absorption of
camphor, menthol, and methyl salicylate in humans. J Clin Pharmacol
44(10):1151-1157.
Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS,
Andahazy M, Story GM, Patapoutian A (2005) Impaired thermosensa-
tion in mice lacking TRPV3, a heat and camphor sensor in the skin.
Science 307(5714):1468-1472.
Reynolds JEF (Ed.), (1989) Martindale The Extra Pharmacopeia. 29th edi-
tion. The Pharmaceutical Press, London.
Nagata K, Duggan A, Kumar G, Garcia-Anoveros J (2005) Nociceptor and
hair cell transducer properties of TRPA1, a channel for pain and hearing.
J Neurosci 25(16):4052-4061.
Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC,
Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian
82
Zuccarini, Soldani
A (2002) A heat-sensitive TRP channel expressed in keratinocytes.
Science 296:2046-2049.
Robertson JS, Hussain M (1969) Metabolism of camphors and related com-
pounds. Biochemical Journal 113(1):57-65.
Schmiedeberg O, Meyer H (1879) Hoppe-Seyl Z 3:422.
Shimamoto T (1934) Sci Pap Iet Phye Chem Res, Tokyo 529:52-58, 59-
62.
Siegel E, Wason S (1986) Camphor toxicity. Pediatr Clin North Am
33(2):375-379.
Sweetman SC (ed.), (2005) Martindale: The Complete Drug Reference. 34th
edition. The Pharmaceutical Press, London.
Valdez JS, Martin DK, Mayersohn M (1999) Sensitive and selective gas
chromatographic methods for the quantitation of camphor, menthol
and methyl salicylate from human plasma. J Chromatogr B Biomed Sci
Appl 729(1-2):163-171.
Wade A (ed.) (1977) Martindale The Extra Pharmacopeia. 27th edition. The
Pharmaceutical Press, London.
Wahlgren CF (1995) Measurement of itch. Semin Dermatol 14:277-284.
Wand MD, Thompson JA (1986) Cytochrome P450-catalyzed rearrangement
of a peroxyquinol derived from butylated hydroxytoluene. Involvement
of radical and cationic intermediates. J Biol Chem 261:14049-14056.
Xu H, Blair NT, Clapham DE (2005) Camphor activates and strongly desen-
sitizes the transient receptor potential vanilloid subtype 1 channel in a
vanilloid-independent mechanism. J Neurosci 25(39):8924-8937.
Xu H, Delling M, Jun JC, Clapham DE (2006) Oregano, thyme and clove-
derived ßavors and skin sensitizers activate speciÞc TRP channels. Nat
Neurosci 9:628-635.
  • ... Camphor tree is native to China, India, Mongolia, Japan and Taiwan and a variety of this fragrant evergreen tree is grown in Southern United States; especially in Florida [1,2]. Camphor is obtained through steam distillation, purification and sublimation of wood, twigs and bark of the tree [3]. There are many pharmaceutical applications for camphor such as: Asthma, topical analgesic, antiseptic, antispasmodic, anti-pruritic, anti-inflammatory, antiinfective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant and etc. [3][4][5]. ...
    ... Camphor is obtained through steam distillation, purification and sublimation of wood, twigs and bark of the tree [3]. There are many pharmaceutical applications for camphor such as: Asthma, topical analgesic, antiseptic, antispasmodic, anti-pruritic, anti-inflammatory, antiinfective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant and etc. [3][4][5]. Camphor is easily absorbed through the skin, and also can be administrated by injection, inhalation and ingestion [3,6]. ...
    ... There are many pharmaceutical applications for camphor such as: Asthma, topical analgesic, antiseptic, antispasmodic, anti-pruritic, anti-inflammatory, antiinfective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant and etc. [3][4][5]. Camphor is easily absorbed through the skin, and also can be administrated by injection, inhalation and ingestion [3,6]. ...
  • ... Camphor tree is native to China, India, Mongolia, Japan and Taiwan and a variety of this fragrant evergreen tree is grown in Southern United States; especially in Florida [1,2]. Camphor is obtained through steam distillation, purification and sublimation of wood, twigs and bark of the tree [3]. There are many pharmaceutical applications for camphor such as: Asthma, topical analgesic, antiseptic, antispasmodic, anti-pruritic, anti-inflammatory, antiinfective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant and etc. [3][4][5]. ...
    ... Camphor is obtained through steam distillation, purification and sublimation of wood, twigs and bark of the tree [3]. There are many pharmaceutical applications for camphor such as: Asthma, topical analgesic, antiseptic, antispasmodic, anti-pruritic, anti-inflammatory, antiinfective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant and etc. [3][4][5]. Camphor is easily absorbed through the skin, and also can be administrated by injection, inhalation and ingestion [3,6]. ...
    ... There are many pharmaceutical applications for camphor such as: Asthma, topical analgesic, antiseptic, antispasmodic, anti-pruritic, anti-inflammatory, antiinfective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant and etc. [3][4][5]. Camphor is easily absorbed through the skin, and also can be administrated by injection, inhalation and ingestion [3,6]. ...
    Article
    Full-text available
    Camphor, menthol, and methyl salicylate occur in numerous over-the-counter products. Although extensively used, there have been no estimates of human exposure following administration via dermal application. Furthermore, there is little information about the pharmacokinetics of those compounds. Our purpose of this study and literature review about camphor is to gain knowledge of the long history, wide variety and extensive applications of camphor both in traditional and modern medicine. In this paper our focus is on the use of camphor as a remedy for daily minor problems as well as perhaps providing a new treatment or protection against some other serious and life threatening diseases like Asthma, diabetes, cancer and furthermore for the treatment of memory disorders in Alzheimer’s patients and perhaps improving the brain function in patients with Autism.
  • ... Camphor tree is native to China, India, Mongolia, Japan and Taiwan and a variety of this fragrant evergreen tree is grown in Southern United States; especially in Florida [1,2]. Camphor is obtained through steam distillation, purification and sublimation of wood, twigs and bark of the tree [3]. There are many pharmaceutical applications for camphor such as topical analgesic, antiseptic, antispasmodic, antipruritc, antiinflammatory, anti infective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant, etc. [35]. ...
    ... There are many pharmaceutical applications for camphor such as topical analgesic, antiseptic, antispasmodic, antipruritc, antiinflammatory, anti infective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant, etc. [35]. Camphor is easily absorbed through the skin and can also be administrated by injection, inhalation and ingestion [3,6]. ...
    ... Camphor also can be potential radiosensitizing agent in radiotherapy. Treatment with camphor prior to a radiation showed the reduced growth of tumor volume [3]. ...
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    Full-text available
    Introduction: The purpose of this literature review is to gain knowledge of the long history, wide variety and extensive applications of camphor both in traditional and modern medicine. Camphor (Cinnamomum camphora) which is obtained from the wood of camphor tree, has been used for centuries and throughout the world as a remedy for treating variety of symptoms such as inflammation, ingestion, infection, congestion, pain, irritation, etc. The studies have shown that some of the components of Cinnamomum camphora have suppressive and anti­mutagenic effect in number of human cancer cells without harming the healthy cells. In this paper our focus is on the use of camphor, as a remedy for daily minor problems as well as gathering some information about the new applications of this traditional medicine to treat or prevent some other serious, life threatening diseases like cancer, diabetes. We hope to get the attention of researchers for conducting more studies on the effects of camphor on patients with memory and brain disorders as well.
  • ... For example, camphor activated TRPV3 and heterologously expressed TRPV1, although its activity was somewhat less than that of capsaicin, the analgesic activity of which is also associated with TRPV1 desensitization. On the other hand, it was observed that camphor desensitized TRPV1 more quickly and perfectly than capsaicin [24,28]. The exposure to vapor phase camphor attenuated nasal symptoms (sneezing and nasal rubbing) induced by toluene diisocyanate (TDI) through the suppression of the production of neuropeptides, such as substance P (SP), calcitonin gene related peptide (CGRP) and nerve growth factor (NGF) in rats. ...
    Article
    Full-text available
    TRPA1 has been proposed to be associated with diverse sensory allergic reactions, including thermal (cold) nociception, hearing and allergic inflammatory conditions. Some naturally occurring compounds are known to activate TRPA1 by forming a Michael addition product with a cysteine residue of TRPA1 through covalent protein modification and, in consequence, to cause allergic reactions. The anti-allergic property of TRPA1 agonists may be due to the activation and subsequent desensitization of TRPA1 expressed in sensory neurons. In this review, naturally occurring TRPA1 antagonists, such as camphor, 1,8-cineole, menthol, borneol, fenchyl alcohol and 2-methylisoborneol, and TRPA1 agonists, including thymol, carvacrol, 1'S-1'- acetoxychavicol acetate, cinnamaldehyde, α-n-hexyl cinnamic aldehyde and thymoquinone as well as isothiocyanates and sulfides are discussed.
  • Article
    Binary gas diffusivities DAB’s are extremely useful in the analysis/design of mass transfer systems and to develop correlations. This study used an unsteady experimental method to determine DAB’s in gas pairs starting with a sublimating solid (A) such as naphthalene or camphor and air (B). The cumulative fractional mass transferred from the surface of a solid A sphere placed concentrically within an isothermal spherical enclosure was followed gravimetrically with time. The experimental DAB,exp for the gas pair was determined by nonlinear regression using the solution to a transient, one-dimensional (radial) diffusion model. The model’s Case 1 option assumed impermeability (no flux of gas A) at the enclosure’s outer surface, while Case 2 assumed zero concentration of gas A at the same location. For naphthalene–air, DAB,exp overestimated the literature values, the errors ranging from −110 to −185% for Case 1 and −21 to −65% for Case 2. For camphor–air, the error in DAB,exp was −36% for Case 1 and −16% for Case 2. DAB,exp for camphor in atmospheric air is herein reported for the first time. Potential improvements to the experiments include automation of the sphere melt-casting process and tighter control of the enclosure’s environmental conditions. Likewise, the theoretical model could be extended to three dimensions with multicomponent diffusion to assess the effect of air humidity on the transport of gas A. This is the first attempt to determine DAB,exp for naphthalene–air and camphor–air from an unsteady sublimation–diffusion experiment and to model the results using rigorous mass transport theory.
  • Article
    p align="center"> ABSTRAK Penelitian dilaksanakan bertujuan untuk mengeksplorasi potensi senyawa metabolit sekunder tanaman rumput mutiara ( Hedyotis corymbosa (L.) Lamk.) dalam bentuk esktrak. Penelitian ini diharapkan memberikan informasi yang lebih lengkap terhadap potensi penggunaan tanaman tersebut sebagai obat tradisional. Identifikasi komponen senyawa metabolit sekunder dilakukan dengan metode Gas Chromatograph Mass Spectrometri (GCMS). Hasil GCMS menunjukkan terdapat 20 senyawa yang terindetifikasi yang berasal dari golongan flavanol, monoterpena, triterpena, sikloterpena, seskuiterpena, fenolat, asam organik, flavon. Senyawa yang teridentitfikasi adalah: catechol , camphene , limonene , myrcene , pinene , camphor , cineole , geraniol , citronellol , gallic acid , ascorbic acid , β caryophyllene , β elemene , β farnesene , β selinene , apigenin , kaempferol , luteolin , catechin , betulinic acid . Beberapa fungsi penting senyawa-senyawa tersebut diantaranya adalah antioksidan, antibakteri, anti inflamasi, anti kanker, anti tumor, anti leukimia, hepatoprotektor, anti alergi, ekspektoran, hipoglikemia, hipokolesterol, antitusif, analgesik, kemo protektor.
  • Article
    Compositional characteristics of the essential oils of four Ocimum spp., namely Ocimum adscendens Willd., Ocimum gratissimum L., Ocimum tenuiflorum L. and Ocimum americanum L. were examined using GC-FID, GC-MS, and hierarchical cluster analyses from peninsular India. The essential oil content varied from 1.0% to 2.0% in different Ocimum spp. Altogether eighty-four constituents, corresponding to 89.9−96.5% of the total oil compositions were identified. Major constituents of O. adscendens oil were eugenol (47.6%), (E)-caryophyllene (15.7%) and β-elemene (11.3%). O. gratissimum oil was characterized by the presence of higher amounts of eugenol (52.9%), caryophyllene oxide (7.2%) and (Z)-β-ocimene (3.5%). Major constituents of O. tenuiflorum oil were methyl eugenol (50.9%), caryophyllene oxide (7.5%) and (E)-caryophyllene (5.5%). Moreover, the oil of O. americanum was dominated by camphor (41.8%), limonene (7.1%), α-pinene (6.2%), β- selinene (5.6%) and camphene (5.0%). To the best of our knowledge, a detailed essential oil profile of O. adscendens is being reported for the first time.
  • Article
    White turmeric (Curcuma zedoaria (Christm.) Roscoe) has been used as traditional medicine by Indonesian people. The chemical constituents of essential oil of white turmeric were collected in 5 hours of the steam-distillation, and then were investigated by GC-MS. Furthermore, the essential oils were fractionated every hour of 5 hours distillation and were identified twenty compounds. The major compounds of the oil is camphor (49.51 %), isobornyl alcohol (12.66 %), borneol (4.23 %), furanodiene (3.61 %), furanodienone (3.49 %), 1,8-cineole (3.42 %), camphene (2.28 %), beta-pinene (1.75 %), 2-nonanon (0.76 %) and germacrene-D (1.19 %). The main component of the essential oils is champhor, which is the highest concentration lie in the 3rd of collection times (50.71 %). The toxicity of the essential oils was subjected toward Artemia salina Leach. The results indicated that the essential oils from 5th of collection times by using steam-distillation have the highest toxicity, and the LC50 value is 3.25 ppm (v/v). The oil might be classified as anti-tumor activity.
  • Article
    The present study investigated the effects of repeated administration of Korodin®, a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin® or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin® administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin®. The excellent tolerability and safety of Korodin®, even after a total consumption of 80 drops, was confirmed.
  • Article
    Investigations have been made of the reactions of e–aq, OH, O–, H, (SCN)–2, Br–2 and CO–2 with camphor. Rate constants of 3.1 × 109, 4.1 × 109 and 1.6 × 109 dm3 mol–1 s–1 have been obtained for the reactions of e–aq, OH and O–, respectively. The other radicals did not react at measurable rates. The spectra of the radicals resulting from the reactions with camphor have been determined. The radicals formed by action of e–aq can exist in different protonated forms with pKa of 12.0 but identical radicals, R·, appear to be formed from OH (in neutral solution) and O–(in alkaline solution). The R· radicals react with each other with 2k= 8.7 × 108 dm3 mol–1 s–1 and with oxygen with k= 1.3 × 109 dm3 mol–1 s–1, giving RO2· radicals. The RO2· radicals react with each other with 2k= 3.4 × 108 dm3 mol–1 s–1.
  • Analytical methods using gas chromatography–flame ionization detection (GC–FID) for the quantitation of camphor and menthol and GC–MS for the quantitation of methyl salicylate have been developed for measurement of low concentrations from human plasma. Anethole serves as the internal standard for camphor and menthol and ethyl salicylate serves as the internal standard for methyl salicylate. Plasma samples undergo multiple, sequential extractions with hexane in order to provide optimal recovery. For menthol and camphor, the extracting solvent is reduced in volume and directly injected onto a capillary column (Simplicity-WAX). Extracted methyl salicylate is derivatized with BSTFA prior to injection onto a capillary column (Simplicity-5). Between-day variation (% RSD) at 5 ng/ml varies from 6.2% for methyl salicylate to 13.5% for camphor. The limit of detection for each analyte is 1 ng/ml and the limit of quantitation is 5 ng/ml. These analytical methods have been used in a clinical study to assess exposure from dermally applied patches containing the three compounds.
  • Article
    Full-text available
    Pruritus measurement is problematic, because of its subjective nature and poor localization. Ratio scales enhance the usefulness of the visual analogue scale (VAS) by reducing variation; other scales such as the generalized labelled magnitude scale may also be useful. Pruritus neuroanatomy includes peripheral receptors, peripheral and central nerves, ascending and descending spinal pathways, and several brain regions. Pruritus receptors include Merkel discs and free nerve endings, and itch receptors have fast or slow adaptation. In this review, we discuss the pathophysiology of pruritus in atopic dermatitis, psoriasis and scabies. Pruritus treatment is reviewed for topical agents and antihistamines. Future research directions are suggested.
  • Article
    Camphor has been found to decrease the rate of oxygen consumption by rat kidney mitochondria. The rate of oxygen consumption is nearly halved by the addition of 8 X 10(-3) M camphor. It is suggested that camphor may be of use in oxygenating tumours prior to radiotherapy.
  • Article
    Oxidative metabolism in whole cells of Escherichia coli strain 82/r was inhibited by d-camphor when glucose, pyruvate, or succinate was used as substrate. Inhibition was not due to lower surface tension in d-camphor-treated cell suspensions nor was it a function of cell permeability. Succinic, lactic, and NADH-oxidase activities were inhibited in alumina powder cell-free extracts (80 mug of protein/ml) by d-camphor (1100 mug/ml). NADH: and succinic: DCPIP oxidoreductase enzymes were unaffected by d-camphor. Menadione (vitamin K3) restored succinic, lactic, and NADH-oxidase activities in d-camphor-inhibited cell-free extracts. Concentrations of menadione used to restore succinic and NADH oxidase activities were not stimulatory in non-camphor-treated extracts. Succinic oxidase activity in d-camphor-inhibited cell-free extracts was also restored by ubiquinone (Q6) but not by vitamin K1. These results are interpreted to indicate that d-camphor may affect quinone function in E. coli.
  • Article
    Full-text available
    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.
  • Article
    The perceptual effects of camphor on hairy skin were measured in a psychophysical experiment. Subjects rated the intensity and quality of sensations produced when a solution of 20% camphor (in a vehicle of ethanol and deionized H2O) was applied topically to the volar forearm. Under conditions in which skin temperature was varied either from 33-43 degrees C or from 33-18 degrees C, it was found that camphor increased the perceived intensity of the cutaneous sensations produced during heating and cooling. Although camphor's effect appeared to be greater during warming, neither effect was large. Camphor also produced a significant increase in the frequency of reports of "burning." It is concluded that camphor is a relatively weak sensory irritant that may have a modest excitatory effect on thermosensitive (and perhaps nociceptive) cutaneous fibers.
  • Article
    Camphor ingestion is a toxic ingestion that is seen infrequently in the emergency department. It is remarkable for its rapidity of action and toxicity. A case of camphor ingestion that displayed toxic effects is presented. The pharmacology, manifestations, and management of this readily available substance are discussed.
  • Article
    The frequency of sister-chromatid exchanges (SCE) in mouse bone marrow exposed to gamma-irradiation was used to assess the radiomodifying effect of camphor. Hoechst 33258 plus Giemsa was used for SCE analysis. The radiation-induced SCE frequency was significantly low after a single dose of camphor (0.5 microM/g b.w.) administered 30, 45 or 60 min before irradiation; the effect was enhanced with increasing time intervals.
  • Article
    The p-peroxyquinol derived from butylated hydroxytoluene, 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone, was degraded by the ferric form of rat liver cytochrome P-450, and the resulting products and their mechanisms of formation were investigated. Quinoxy radical BO. from homolysis of the O-O bond reacted by competing pathways; beta-scission yielded 2,6-di-t-butyl-p-benzoquinone, and rearrangement with ring-expansion produced an oxacycloheptadienone free radical (X(.)). This rearranged radical was stabilized by the captodative effect that facilitated competitive interactions with the P-450 iron-oxo complexes formed during O-O bond scission. Approximately 15% of X(.) was captured by oxygen rebound with a hydroxyl radical from the P-450 complex (FeOH)3+ to form a hemiketal, that led to the ring-contracted product 2,5-di-t-butyl-5-(2'-oxopropyl)-4-oxa-2-cyclopentenone by spontaneous rearrangement. The major fraction of X(.), however, underwent electron transfer oxidation to form the corresponding cation. Hydration of this cation produced the ring-contracted product, and proton elimination (or, alternatively, direct H(.) removal from X(.) led to the product 2,7-di-t-butyl-4-methylene-5-oxacyclohepta-2,6-dienone. The findings indicate that cytochrome P-450 intermediate complexes are mainly responsible for oxidation of X(.). The results complement our previous study with 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone (Thompson, J. A., and Wand, M. D. (1985) J. Biol. Chem. 260, 10637-10644), demonstrating competitive heterolytic and homolytic mechanisms of O-O bond cleavage, and competitive rebound and oxidation processes when a substrate-derived radical interacts with P-450 complexes.