endodontics

Editor:
SAMUEL SELTZER, DDS
Department of Endodontology
School of Dentistry
Temple Universit,y
3223 North Broad Street
Philadelphia, Pennsylvania 19140

Biologic properties of eugenol and zinc

oxide--eugenol
A clinically oriented review

Kenneth Markowitz, DDS,(’ Michael Moynihan, DDS, Mintsai Liu, DDS, MA,b and
Syngcuk Kim, DDS, PhD,C New York, N.Y.

DIVISION OF ENDODONTICS AND LABORATORY OF ORAL PHYSIOLOGY, SCHOOL OF DENTAL

AND ORAL SURGERY, COLUMBIA UNIVERSITY

Eugenokontaining dental materials are frequently used in clinical dentistry. When zinc
oxide-eugenol (ZOE) is applied to a dentinal cavity, small quantities of eugenol diffuse through the
dentin to the pulp. Low concentrations of eugenol exert anti-inflammatory and local anesthetic
effects on the dental pulp. Thus use of ZOE temporary filling may facilitate pulpal healing; on the
other hand, high eugenol concentrations are cytotoxic. Direct application of eugenol to pulp tissue
may reslult in extensive tissue damage. The ability of ZOE-based endodontic sealers to influence
periapical tissue healing is considered in view of eugenol’s anti-inflammatory and toxic properties.
(ORAL SURC ORAL MED ORAL PATHOL 1992;73:729-37)

D entists frequently use zinc oxide-eugenol (ZOE)

as a temporary filling and as a cement for provisional
pounds are related to phenol, which is a weakly acidic
alcohol. Phenol also has anesthetic effects and was one
restorations. Eugenol-soaked pellets are occasionally of the first antiseptics used in surgery. Phenol and the
placed on vital exposed pulps as a sedative dressing. closely related compound cresol are irritating and
These practices are not always successful or without somewhat caustic to tissue. Eugenol is found in oil of
controversy.’ Both beneficial and harmful effects have clove, which is primarily used as a spice and food pre-
been attributed to eugenol.2 To date few studies of servative. When eugenol is mixed with zinc oxide, a
eugenol’s physiologic: effects on the dental pulp have chelation reaction occurs and zinc eugenolate is
been undertaken. formed. ZOE is a common constituent of temporary
Eugenol and related compounds have a long history filling, material, cavity base, liners, and root canal
of use by dentists.3 Eugenol, thymol, and other essen- sealers. When examined ultrastructurally, ZOE ce-
tial oils have plleasant smells, germicidal activity and ment consists of grains of zinc oxide embedded in a
some degree of local anesthetic effects. These com- zinc eugenolate matrix. Because separate zinc eu-
genolate units are held together by van der Waals
forces and particle interlocking, ZOE cements are
aAssistant Clinical Profeissor; also Member, Division of Research
weak mechanically.4 Products such as IBM (L.D.
and Development, Block Drug, Inc. Jersey City, N.J.
bAssistant Professor.
Caulk, Milford, Del.) are reinforced ZOE cements
CDirector. with improved mechanical properties.
7/15/35642 When exposed to aqueous media such as saliva or
729

‘\
730 Mavkowitz et al.

Pulpal Tissue

Fig. “i. After mixing of zinc oxide and eugenol, zinc eugenolateis formed. Water stowiy breaks down zinc
eugenolate,allowing free eugenoi to diffuse into the pulp through dentinal tubules.

dentinal fluid, hydrolysis of zinc eugenolate occurs, amounts of eugenol to the pul~.~ Flume8 considered
yielding eugenoi and zinc hydroxide. Eugenol hber- ZOE paste a good ““control deiivery system” to
ated from ZOE can diffuse through dentin and into deposit pharmacologically active but subtoxic levels
the saliva. Hume5 filled occlusal cavities in extracted of eugenol to the pulp,
human teeth with zinc oxide mixed with tritium-
TOXIC EFFECTS OF ~U~E~OL
labeled eugenol and found that eugenol was slowly
released into the dentin and pulpal fluid. A schematic Eugenol is bactericidal at relatively high concen-
diagram illustrating the release and dentinal diffusion trations ( 10m2to low3 mol/L). Dentin adjacent to a
of eugenol from a ZOE filling is shown in Fig. 1. In ZOE-filled cavity may be exposed to bactericidal eu-
the dentin below the filling, concentrations of 10m2 genol levels. ZOE fillings act to prevent bacteria!
mol/L were reached. Fluid in the pulp space obtained penetration of dentinal cavities9 This clinically im-
concentrations of 10e4mol/L. These concentrations portant effect was attributed to the ability of ZOE to
were maintained for more than 1 week. The release of prevent microleakage of contaminated oral fluids.
eugenol was not markedly affected by the zinc oxide/ Direct measurements of leakage suggest that the seal
eugenol mix ratio. The release of eugenol was affected created by ZOE is not particularly tight when com-
by the thickness of remaining dentin between the pulp pared with other materials.” Thus the antibacterial
chamber and the ZOE-filled cavity. Meryon et a1.6,7 effects of ZOE fillings may contribute to their clini-
found that thick dentin sections provided a better cal effectiveness. Brief exposure to lo-’ mol/L eu-
protective barrier than thin sections. Calcium in the genol kills mammalian cells. Prolonged exposure to
dentinal tubules chelates eugenol, limiting its ability LOW3 mol/L also kills cells. Hume’s data from these
to diffuse through dentin. Binding of eugenol to the studies show that eugenol concentrations that diffuse
organic matrix of dentin, especially collagen, also through dentin are not cytotoxic. Even lower concen-
slows diffusion. Modified ZOE cements were also trations, however, can inhibit cell respiration and cell
demonstrated to release less eugenol and exert fewer division.” Recent studies tested the ability of phenolic
toxic effects. It has been suggested that acid-etched compounds to inhibit enzymes in cultured rat pulp
dentin may facilitate diffusion of potentially toxic cells. Inhibitory eugenol concentrations were signifi-
Volume 73 Properties of eugenol 731
Number 6

cantly higher than concentrations that had anti- caries and traumatic restorative procedures. The fol-
inflammatory eflrects.I2 Various biochemical mecha- lowing sections examine the effects of eugenol on var-
nisms have been proposed to explain the cytotoxicity ious components of the inflammatory process. This
of eugenol. For instance, eugenol can be oxidized by provides a basis for understanding effects that eugenol
peroxidase enzymes t.o a product that is toxic to rat has on both pulpal and periapical tissue.
hepatocytes. I3 Eugenol and related compounds were
ANESTHETIC PROPERTIES OF EUGENOL
shown to have a high affinity for plasma membranes
because of their lipid solubility. This is hypothesized The ability of eugenol to allay tooth pain is the main
to contribute tso cell damage.14 Cotmore et a1.t5 reason it is so widely used in dentistry. Chewing on
reported that eugenol can uncouple oxidative phos- cloves produces topical anesthesia of the oral mucosa
phorylation in mitochondria. These toxic effects of (personal observation). Kozam21 observed that eu-
eugenol may explain why direct application of eu- genol irreversibly blocked the conduction of action
genol-soaked cotton pellets to pulp tissue appears to potentials in the frog sciatic nerve. Brodin and
cause an exacerbation of pulpitis symptoms. Direct Rded22>23 tested the effect of eugenol and ZOE
pulp capping with ZOE evokes mild to more severe cement on compound action potentials in the phrenic
pulpal inflammatory response.‘5-17 Watts and Pater- nerve. At low concentrations eugenol inhibited nerve
son1* tested the effects of ZOE-containing cements on activity in the reversible manner like a local anes-
germ-free rats after sterile pulp exposure. When the thetic. After exposure to high concentrations of
ZOE material was sleparated from the exposed pulp eugenol, nerve conduction was irreversibly blocked,
by dentin chips, the pulp exhibited minimal inflam- indicating a neurotoxic effect. Eugenol also reduced
matory change 28 days after pulp capping. Placement synaptic transmission at the neuromuscular junction.
of the ZOE materia!l in direct contact with the pulp Ozeki24 found that eugenol slowed nerve conduction
tissue resulted in chronic inflammation and necrosis. in crayfish neurons and made them less excitable.
Because this test was conducted with a commercial These results are partially explained by the observa-
ZOE cement, the possible toxic role of other sub- tion made in the same article that eugenol makes the
stances besides zinc oxide and eugenol must be con- crayfish nerve cell membrane more permeable to po-
sidered. Severe inflalmmatory reactions to ZOE ce- tassium ions; this lowered the membrane resistance.
ments applied to deep cavities were reported in human These eugenol-treated motor neurons also appeared
teeth by BrannstrGm and Nyborg.19 These studies to release less neurotransmitter. Additional studies
highlight an important principle concerning eugenol’s such as Ozeki’s, where the effect of eugenol and other
clinical use. Direct (contact between vital tissue and drugs are measured at the cellular level, are needed to
eugenol-containing material can cause damage to tis- determine this drug’s mechanisms of action. Trow-
sue. bridge et a1.25 found that eugenol liquid and ZOE
paste placed into the canine teeth of cats blocked in-
PULPAL INFLAMMATION
tradental nerve activity (INA) induced by compound
Inflammation is the response of tissues to injury and 48/80. The reversibility of this effect was not deter-
infection. The dental pulp is subject to bacterial inva- mined. The mechanism by which compound 48/80
sion from caries and trauma from drilling and other induces INA is not known. It is thought to act on sen-
restorative procedures. Inflammation is charcterized sory nerves indirectly through degranulation of mast
by an increase in blood flow, increase in vascular cells.26 Zinc oxide mixed with paraffin oil had no ef-
leakage, and sensitization of nerve endings. These re- fect on INA. Although the depth of cavities used in
sponses lead to’the principal symptoms of inflamma- this study was not stated, it appears that eugenol lib-
tion, swelling, and pain. In addition, various blood- erated from ZOE paste can diffuse into the pulp in
borne cells enter inflamed tissue. In most organs in- sufficient concentrations to inhibit compound 48/80-
flammation serves a useful function, limiting the induced INA. INA recorded in human teeth corre-
extent of damage and initiating healing. In the dental lates with the sensation of pain.27 It may be argued
pulp inflammation may lead to a less favorable that sedation of the pulp is undesirable because it
outcome. The pulp -is enclosed in the rigid confines of merely masks the symptoms of pulpal inflammation.
the dental hard tissues and lacks collateral circula- According to our contemporary view of inflamma-
tion. This low-compliance environment does not allow tion, sensory nerve fibers and their function are known
the pulp to swell during the inflammatory response.20 to play an important role in the generation of the in-
Instead, the pulpal tissue pressure increases to an ex- flammatory response. Sensory nerves in the dental
tent that may I.ower pulpal blood flow. Because of this pulp contain vasoactive peptides such as substance P,
unique functional property, irreversible damage and calcitonin gene-related peptide, and others.28, 29These
even pulp death are frequent consequences of deep vasoactive peptides are capable of causing vasodila-
932 Markowitz et al. OR~L§rxci ORAL M-ED ORAL PATH~L
June 1992

Fig. 2. Eugenol release from a ZOE cement filling can lessen an inflammatory responseby suppressing
prostaglandin formation and possibly through its depressanteffect on sensory nerves.

tion and an increase in tissue pressure in the dental tion has been described in many tissues3* The obser-
pul~.~O-~~Stimulation of the inferior alveolar nerve vation that eugenol inhibits nerve activity may be
causes a similar increase in pulpal blood flow (PBF).33 critical in understanding its possible anti-inflamma-
Wakasaki et al. 34,35 found that neuropeptide-con- tory effects, because nerve activity and the vascular
taining sensory nerves surround pulpal blood vessels components of the inflammatory response appear to
and send processes to the odontoblast and deep den- be related.
tinal areas. We demonstrated thai ionic agents that
stimulate intradental nerve activity such as hyper- UGENQL INFLUENCES OTHER
INFLAMMATORY PATHWAYS
tonic sodium chloride and potassium chloride also
cause an increase in PBF. 36 Recent work shows that Injury such as traumatic cavity preparation trig-
blocking intradental nerve activity with 1% lidocaine gers a number of cellular and biochemical processes.
solution attenuates the PBF response to KC1 After injury leukocytes emigrate from blood vessels
(Markowitz et al., in preparation). In addition, re- and enter the pulpal connective tissue.39 At high con-
peated applications of the C fiber stimulant and de- centrations eugenol stimulates release of superoxide
sensitizing agent capsaicin also causes attenuation of from neutrophils. This increases tissue damage at the
the PBF response to KC1 (Pert1 et al., in preparation). site of inflammation. At these same concentrations
These experimental results indicate that the pulpal C eugenol was toxic to these cells.40 Eugenol inhibits
fibers are important in the generation of the inflam- neutrophil chemotaxis and superoxide anion genera-
matory response in the dental pulp. This involvement tion at low (noncytotoxic) concentrations4” In this
of sensory nerves in inflammation is due to the dual study eugenol had a more potent effect than other
role played by these fibers. Not only do they relay in- phenolic compounds tested. At low concentrations
formation to the central nervous system, but they also eugenol may protect tissue from damage by inhibit-
release vasoactive agents into the peripheral tissue at ing neutrophil function and by removing harmful free
the site of injury and through the axon reflex into ad- radicals. In the pulp histologically observed inflam-
jacent areas.37 This process of neurogenic inflamma- matory reactions were induced in monkey teeth by the
Volume 73 Properties of eugenol 733
Number 6

. Induces cell death. l Inhibits prostaglandins

. Unknown vascular effect. synthesis.
. Inhibits cell growth l Inhibits nerve activity.
and respiration. l Inhibits white cell chemotaxis.

Fig. 3. Effects of eugenol on tissue appears to be highly dependenton tissue concentration of eugenol. High
concentrations appear to exert cytotoxic effects. Low concentrations are capable of anti-inflammatory activ-
ity.

placement of leaky temporary fillings or human car- chemotaxis and the production of lipoxygenase prod-
ious dentin in deep cavities. These treatments expose ucts.48 Traumatic cavity preparation caused leuko-
the pulp to bacterial irritants. Both ZOE and calcium cyte migration into the area of the pulp adjacent to the
hydroxide paste allowed resolution of the inflamma- deep cavity. The numbers of polymorphonuclear leu-
tory response and the formation of reactive dentin. kocytes and lymphocytes reached its peak 3 to 4 hours
However, removal of bacterial irritants is the most after cavity preparation. In teeth with the deep cav-
important factor in pulpal healing. The effect of eu- ities filled with ZOE paste, a delay of 2 hours was re-
genol on leukocyte function may also contribute to the quired to reach peak numbers of these inflammatory
resolution of the inflammatory response.42 Eugenol, cells. There was also a rise in the production of leu-
like other phenolic compounds, removes free radicals kotrienes after cavity preparation. As was the case
from tissue and inhibits cyclooxygenase.43, 44 Eugenol with polymorphonuclear neutrophils and lympho-
has been found to act as a competitive inhibitor of cytes, ZOE caused a delay in the time to peak
prostaglandin H synthase, preventing binding of concentrations of leukotrienes compared with unfilled
arachidonic acid to ,the enzyme.45 Oil of clove has teeth. The effect of ZOE on leukotrienes and inflam-
been found to be a potent inhibitor of thromboxane matory cell migrat,ion was not as marked as the effect
formation and platelet aggregation in human blood in on cyclooxygenase products observed with the same
vitr6.46 In this stu d y oil of clove inhibited platelet ag- methods.
gregation evokeld by epinephrine and collagen. Plate- The results of this group of studies are significant
let aggregation and hemostasis are an important part since prostaglandins and leukotrienes are important
of the response to injlury and the initiation of the in- mediators of the inflammatory process. PGE2 and
flammatory prolcess. Platelets release vasoactive sub- some leukotrienes increase blood flow and vascular
stances when they aggregate at the site of injury. ZOE permeability, and at physiologic concentrations sen-
fillings have been found to reduce markedly pros- sitize nerve endings, resulting in a lowered pain
taglandin E2 (PGEz), thromboxane, and the PGEl threshold. Ahlberg49 induced prolonged INA re-
metabolite DHK-prastaglandin formation in rat teeth sponses to heat application by repeated application of
subjected to traumatic cavity preparation.47 In the heat to cat teeth. Treatment of the cats with the cy-
case of PGE2 and its metabolite, ZOE filling caused clooxygenase-inhibiting drug indomethacin abolished
the levels to fall to those below that found in normal this prolonged response to heat. The results were ex-
pulps. Measurement of tritium-labeled eugenol levels plained in terms of prostaglandins sensitizing the in-
in the pulp in this study yielded a level of 1W5 mol/L tradental nerves to become hyperresponsive to heat. It
that is sufficient to cause metabolic impairment.” It is likely that heat and traumatic drilling initiates sev-
should be noted that the cavity prepared in this study eral pathways of the inflammatory process, some of
involved placing ZOE paste directly in contact with which may be sensitive to eugenol. Fig. 2 shows some
tissue at the tip of the pulp chamber. These same in- of the possible anti-inflammatory effects of eugenol.
vestigators studied the effect of ZOE on leukocyte Aspirin and the nonsteroidal anti-inflammatory drugs
734 Markowitz et al. ORAL %JRC~ ORAL MED OR~PATHOL
June 1992

such as ibuprofen have pharmacologic effects simiiar eugenol-induced vasodilation may cause irreversible
to eugenol. These drugs also inhibit prostaglandin vascular changes, leading to pulp necrosis2’, 55
synthesis and alter leukocyte function.50 These phar- Clearly, direct studies of the vascular effects of
macologic properties of eugenol may modify the tis- eugenol and ZOE paste are needed to determine
sue response to injury, allowing a less intense inflam- whether these events occur. The results of these
matory response to occur. studies should determine whether eugenol and ZOE
have undesirable pharmacologic properties or can
~RCUL~T~RY EFFECTS OF EUGENOL help preserve pulp vitality by shielding the pulp from
To date there are few detailed studies of the effects hemodynamic perturbations caused by traumatic
of eugenol or ZOE on pulpal vasculature and blood stimulus. These studies would also provide a physio-
Bow. Humejr studied the effects of eugenol on circu- logic methodology that could be used to test new base-
lation in the rabbit ear. Eugenol caused vasodilation and pulp-capping materials.
and inhibited the response of these vessels to norepi-
nephrine and histamine. Hume hypothesized that va- CLINICAL IMPLICATIONS OF EUGENOL’S
PROPERTIES
sodilation caused by eugenol would result in preven-
tion of toxic accumulations of materials and rapid re- The pharmacologic effects of eugenol are likely to
moval of irritants. Hashimoto et a1.47 found that be complex and to depend on the free eugenol
tritium-labeled eugenol released into the pulp rapidly concentration to which the tissue is exposed. Fig. 3
reached the 1Oe5mol/L levels within 30 minutes after shows that beneficial pharmacologic responses are
the filling of a deep cavity with ZOE paste. This level most probable when the pulp is exposed to low eugeno!
of eugenol in the pulp tissue rapidly declined to basal concentrations. These low concentrations can be ob-
levels within the subsequent 4 hours. This type of de- tained by eugenol diffusion from a ZOE filling
cline in concentration is consistent with rapid micro- through a layer of intact dentin. Placement of a ZOE
circulatory removal of eugenol from the pulp tissue, filling after excavation of deep caries should exert a
because eugenol release from ZOE paste is known to sedative and anti-inflammatory effect. Clinically this
occur during a long time period when studied in ex- should be manifested by a decrease in sensitivity of the
tracted teeth.5 Kim (unpublished observations) ob- tooth to cold, hot, and sweets. Alternatively, high
served that eugenol liquid increased PBF and vessel concentrations capable of cytotoxic effects can be de-
diameter when applied to very deep dentinal cavities. livered to tissues by placing eugenol or ZOE in direct
These effects were measured by intravital microscopy. contact with vital tissue. The evidence strongly sug-
The special anatomic environment of the dental gests that direct pulp capping with eugenol-contain-
pulp make an understanding of the vascular effects of ing materials should be avoided if long-term mainte-
eugenol important. Because the pulp is contained in nance of pulp vitality is to be achieved. Direct place-
the low-compliance environment of the tooth, many ment of a eugenol-soaked pellet over a vital exposure
vasodilators produce a biphasic blood flow response should be done when an endodontic procedure can be
(an increase followed by a decrease).20, 52 Neuropep- performed within a few days.
tides, prostaglandins, bradykinins, and other inflam- Like other drugs, eugenol is not a panacea. The ef-
matory mediators cause vasodilation and leakage of fectiveness of eugenol is limited in the face of severe
fluid from the vasculature. Because the pulp can not tissue injury. In some instances deep caries or trau-
increase in volume like other tissues, inflammatory matic tooth preparation may induce irreversible ef-
substances induce a rise in pulp tissue pressure.53 This fects not amenable to pharmacologic intervention.
increase in tissue pressure causes compression of the Although eugenol may reduce the response to mild
vasculature, especially the thin-walled pulpal trauma, the nature of the pulp’s reaction depends on
venules.20 Eventually this leads to a drop in PBF. the severity of the damage. No pharmacologic treat-
Traumatic procedures, such as full crown preparation ment can mitigate the effect of poor technique. To
without water spray, caused an increase in PBF fol- preserve tooth vitality, there is no substitute for early,
lowed by a later decrease. 54 The eventual decrease in conservative, and atraumatic tooth preparation.
PBF in response to inflammatory mediators is hy-
pothesized to be an important factor leading to pulp USE OF EUGENOL IN ENDODONTIC
QBTURATION
necrosis in response to inflammation caused by caries
and operative procedures. 55 Our hypothesis is that a Sealers used in endodontic obturation often include
large increase in PBF caused by eugenol or ZOE ZOE in combination with a wide variety of other in-
would be undesirable to -the damaged pulp because gredients. Unlike the dental pulp, the periapical tis-
these changes wou.ld be superimposed on preexisting sues are difficult to study directly in vivo. Despite this,
vascular derrangements. By further increasing PBF, various experimental approaches can help us under-
Volume 73 Properties of eugenol 735
Number 6

stand the effects of eu.genol on periapical tissues. As genol to be highly toxic to human cell lines. If this cy-
described in the preceding section, eugenol diffusion totoxicity were to occur in the periapical tissue, heal-
into the dental pulp from a ZOE filling is limited by ing may be delayed or inhibited. Studies with gingi-
an intact dentin barrier. In this relatively dry cavity, val fibroblasts found that periodontal dressings with
free eugenol is released slowly as the eugenolate is ZOE were more cytotoxic than noneugenol dress-
hydrolyzed. In contrast, when used as an endodontic ings. 61 As a result of such studies, periodontal dress-
sealer, ZOE may be placed into direct contact with ings no longer contain eugenol, because it is thought
inflamed or healthy periapical tissue. This type of to delay healing. In another study, also with the use
“wet” interface between ZOE paste and tissue allows of gingival fibroblasts, Briseiio and Willershausen62
the release of large amounts of eugenol into the api- demonstrated cytotoxicity in all the ZOE-based root
cal tissue during a short period of time. At this higher canal sealers tested. These results are in agreement
concentration eugenol has been demonstrated to ex- with studies involving implantation of endodontic
hibit its cytotoxic effects. sealers into subcutaneous tissue of experimental an-
The difficulty in assessing the effect of eugenol on imals. Such studies demonstrate a severe to moderate
periapical tissues is due to the greater importance of inflammatory reaction to eugenol in ZOE-based seal-
cleaning and shaping the canal system. Clinical suc- ers.63In another study an experimental sealer without
cess in endodontics is due to the elimination of micro- eugenol was compared with a similar eugenol-con-
organisms and other antigenic material from the pulp taining material. The sealer without eugenol showed
space and their continued exclusion by the endodon- a higher degree of biocompatibility.64
tic filling. 56 The pharmacologic properties of the Although eugenol is believed to be capable of caus-
sealer are of secondary importance.57 Whether eu- ing persistent inflammation when used in endodontic
genol contributes to the healing process or actually sealers,65 these products have a most impressive clin-
delays healing by causing tissue damage and main- ical record. Studies on animals have shown that
taining the inflammatory reaction remains to be de- eugenol-based sealers provide adequate sealing char-
termined. Many stuldies have been conducted to acteristics yet still display an inflammatory reaction
determine the effects of eugenol, and the discrepancy expected from both the tissue culture and implanta-
between laboratory studies and clinical results ap- tion studies. ZOE-based sealers were found on histo-
pears to be great. Eugenol, in addition to being anti- logic examination to cause a greater degree of in-
bacterial, may have other beneficial effects.8 Eugenol flammation than Ca(OH)z when used as dressings for
may inhibit periapical nerve activity, as has been experimentally produced root perforations in dogs.
shown in the dental pulp. 22 At greater concentrations The teeth treated with Ca(OH)2 exhibited a greater
eugenol may also be toxic to these apical nerves. Both degree of healing, whereas the ZOE group displayed
effects can lessen the perception of pain. Through the a progressive inflammatory reaction that was essen-
inhibition of prostaglandin and leukotriene synthesis, tially equal to the untreated control group.@j In
eugenol may assist in the resolution of periapical in- another study Ca(OH)2 was compared with ZOE as
flammation. Of great relevance to periapical disease a filling material for the root canal systems of primary
is the contribution of prostaglandins, especially PGE2 teeth in dogs. The results showed that the teeth
in bone resorption. Fibroblasts in apical cysts are be- treated with Ca(OH)2 exhibited a lesser inflamma-
lieved to synthesize PGE2 under stimulation by lym- tory reaction at the apex. This was determined by
phocytes. This PGE2 then stimulates osteoclasts to histologic examination and correlated with both clin-
resorb bone.58 These Ieffects of eugenol on neutrophil ical and radiographic evaluation, which confirmed an
chemotaxis and free radical removal can also help to increased amount of bone apposition and a decreased
promote resolutison of apical inflammation.41 Neutro- degree of resorption and abscess formation for Ca-
phils and the free radicals they release damage tissue (OH)2 treated teeth. It should be noted that in the
as well as kill bacteria. 59 Eugenol has been reported cleaning and shaping of the canal systems of these
to affect the cell-me.diated immune response. The teeth, saline solution was used as the irritant. As a re-
feeding of eugenol to Iyoung mice had dose-dependent sult the differences between ZOE and Ca(OH)2 may
effects on cell-mediated immunity. At low doses sup- be due to the greater antibacterial activity of the Ca-
pressor T cells were activated. With higher doses (OH)2, because infection in these teeth may have in-
helper T cells ‘were activated to the point where fluenced the apical response.67 One interesting point
eugenol became toxic to these cells.60 Although the noted by the authors was the type of inflammation
relevance of these re;sults to apical pathology is not caused by each of these agents. Ca(OH)2 caused a
clear, the pharmacologic modulation of cell immunity more acute inflammatory reaction with a faster res-
is likely to be an area of active investigation. olution, whereas the ZOE displayed a more chronic
Experiments with tissues in culture have shown eu- inflammatory response. Recently ,the long-term his-
736 Markowitz et al. QRAL SURG ORAL MED ORAL PATHOL
June 1992

tologic response to a variety of endodontic sealers was inflammatory effects to predominate over its toxic
reported by Pascon et al. Endodontic treatment with potential.
aseptic technique was performed on primate teeth. A
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Even though our knowledge of these materials is far 107.
from complete, it is obvious that the amount of root 17. Cox C, Keall C, Keall H, Ostro E, Bergenholtz G. Biocompat-
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This review of the pulpal and possible apical effects SURGORALMEDORALPATHOL 1977:44:799-805.
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Volume 73 Properties of eugenol 737
Number 6

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