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Journal of Applied Oral Science

Print version ISSN 1678-7757On-line version ISSN 1678-7765

J. Appl. Oral Sci. vol.12 no.2 Bauru Apr./June 2004 



Importance of bacterial endotoxin (LPS) in endodontics


A importância da endotoxina bacteriana (LPS) na endodontia atual



Mario Roberto LeonardoI; Raquel Assed Bezerra da SilvaII; Sada AssedIII; Paulo Nelson-FilhoIV

IChairman, Department of Endodontics, School of Dentistry of Araraquara, UNESP, Araraquara, São Paulo, Brazil
IIGraduate Student in Pediatric Dentistry, Department of Pediatric, Preventive and Social Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
IIIChairman, Discipline of Pediatric Dentistry, Department of Pediatric, Preventive and Social Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
IVAssociate Professor, Discipline of Pediatric Dentistry, Department of Pediatric, Preventive and Social Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil





New knowledge of the structure and biological activity of endotoxins (LPS) has revolutionized concepts concerning their mechanisms of action and forms of inactivation. Since the 1980's, technological advances in microbiological culture and identification have shown that anaerobic microorganisms, especially Gram-negative, predominate in root canals of teeth with pulp necrosis and radiographically visible chronic periapical lesions. Gram-negative bacteria not only have different factors of virulence and generate sub-products that are toxic to apical and periapical tissues, as also contain endotoxin (LPS) on their cell wall. This is especially important because endotoxin is released during multiplication or bacterial death, causing a series of biological effects that lead to an inflammatory reaction and resorption of mineralized tissues. Thus, due to the role of endotoxin in the pathogenesis of periapical lesions, we reviewed the literature concerning the biological activity of endotoxin and the relevance of its inactivation during treatment of teeth with pulp necrosis and chronic periapical lesion.

Uniterms: Bacterial endotoxin (LPS); Gram-negative bacteria, Calcium hydroxide.


O conhecimento mais aprofundado sobre a estrutura e atividade biológica das endotoxinas (LPS) revolucionou os conceitos sobre seu mecanismo de ação e formas de inativação. A partir da década de 80, os avanços tecnológicos na cultura e identificação microbiológica demonstraram que, em canais radiculares de dentes portadores de necrose pulpar e lesão periapical crônica, visível radiograficamente, predominam microrganismos anaeróbios, particularmente os gram-negativos. Como se sabe, os microrganismos gram-negativos, além de possuírem diferentes fatores de virulência e gerarem produtos e sub-produtos tóxicos aos tecidos apicais e periapicais, contêm endotoxina em sua parede celular. Esse conhecimento é particularmente importante, uma vez que a endotoxina é liberada durante a multiplicação ou morte bacteriana, exercendo uma série de efeitos biológicos relevantes, que conduzem a uma reação inflamatória e à reabsorção dos tecidos mineralizados. Tendo em vista o papel da endotoxina na patogênese das lesões periapicais, os autores realizaram uma revisão da literatura específica, abordando suas atividades biológicas e a importância de sua inativação durante o tratamento de dentes portadores de necrose pulpar e lesão periapical.

Unitermos: Endotoxina bacteriana; Gram-negativos; Hidróxido de cálcio.




Bacterial endotoxin (LPS) has been amply studied. In fact, interest in knowledge concerning the structure of bacterial endotoxin, its mechanism of action, and forms of inactivation in both the clinical and laboratory studies is obvious by the fact that in the past 10 years, a total of 28.100 articles have been reported on Medline ( In Dentistry, much research using different in vivo and in vitro methodologies has emphasized the importance of anaerobic bacteria and endotoxin in the etiology of chronic periapical lesions3,9,13,19,21,25,36,42,52,57,63. However, only few articles have evaluated the effect of the presence of LPS in root canals on apical and periapical tissues8,10,32,37,43,55 and some articles have reported the inactivation of LPS toxic properties after endodontic procedures both in vivo and in vitro1,4,6,23,37,42,48,49,55,61,68.



When dental pulp is exposed to the oral cavity due to caries or trauma, it is initially contaminated by predominantly aerobic and facultative microorganisms. Due mainly to the existing nutritional relationships between microorganisms together with the slow decrease of oxygen tension in root canals, a microbial shift takes place leading to a predominance of anaerobic microogranisms60. Since the 1980's, technical advances in microbiological culture and identification have shown that anaerobic microorganisms predominate in root canals of teeth with pulp necrosis and radiographically visible chronic periapical lesion29,30,51,60, especially Gram-negative4. This polymicrobial infection is located not only in the lumen of the root canal and dentinal tubules, but also in apical craters and the entire root canal system29,30,58.

Gram-negative microorganisms have different virulence factors26 and form products and sub-products that are toxic to apical and periapical tissues. They also contain endotoxin in their cell wall33.

Endotoxin, present on all Gram-negative bacteria, is composed of polysaccharides (polymerized sugars), lipids (complexes containing fatty acids) and proteins. Endotoxin can be named lipopolysaccharide (LPS), emphasizing its chemical structure46,65. Lipid A is the region of the endotoxin molecule responsible for its toxic effects11,27,33,34,65. In 1993, Raetz45 published a short review about the synthesis of lipid A and classified the endotoxins as extraordinary lipids.

Besides the chemical structure, much has been studied about the mechanism of action of endotoxins. When free to act, endotoxins do not cause cell or tissue lesions directly, but they stimulate competent cells to release chemical mediators. Researches showed that macrophages are the main target of endotoxins. Thus, endotoxins are not intrinsically venoms. Their effects depend on the host's response, as reported by Lewis Thomas, in The Lives of a Cell: "This oppressive uncontrolled and autodestructive behavior of the host is what makes endotoxin a venom." Furthermore, the same autor wrote: "Endotoxins are read by our tissues as the worst of news. When in contact with an endotoxin, our organism places all of its defenses at disposal with the idea to bombard, block and destroy all the tissue in the area. This appears to generate panic"46.

During endodontic treatment this is particularly significant because endotoxin (LPS) is released during multiplication or bacterial death causing a series of biological effects4,33, which lead to an inflammatory reaction46 and periapical bone resorption59,67.

Even though the bacterial etiology of periapical lesions has already been proven since the classic study of Kakehashi, et al.24, few investigations have evaluated the isolated effect of LPS in contact with apical and periapical tissues8,10,32,37,43,55.

Among all animals, humans are the most sensitive to the effects of endotoxins66, which makes the knowledge of their biological effects on tissues fundamentally important. Endotoxins from vital or nonvital, whole or fragmented bacteria act on macrophages46, neutrophils35 and fibroblasts9, leading to the release of a large number of bioactive or cytokine chemical inflammatory mediators33, such as tumor necrosis factor (TNF)5,33,68, interleukin-1 (IL-1)31,33,68, IL-531, IL-831, alpha-interferon33 and prostaglandins7. Furthermore, LPS is cytotoxic20 and acts as a potent stimulator of nitric oxide production5,68.

LPS also activates Hageman factor (factor XII of coagulation), has a lethal effect on animals33, induces fever21, activates the complement system7,21,34, thus acting in inflammatory response reactions by increasing vascular permeability, neutrophil and macrophage chemotaxis, lysozyme and lymphokine release34, activation of the metabolic cycle of arachidonic acid7,33 being mitogenic for B lymphocytes33 and causing mastocyte degranulation18. In infected root canals, endotoxin can contribute to an increased release of vasoactive neurotransmitter substances in the region of the nerve endings in periapical tissues, causing pain51.

According to Torabinejad, et al.62, the products of arachidonic acid metabolism and the activation of the complement system play an important role in bone resorption that is associated with periapical lesions in human teeth.

Besides causing an inflammatory reaction, LPS adheres irreversibly to mineralized tissues acting as a potent stimulator of bone resorption52,67, acting on the synthesis and release of cytokines that activate osteoclasts22,23, such as IL-1 and TNF, and stimulates the release of prostaglandin-E2 that also influences osteoclasts48,64. In tissue culture, Nair, et al.36 observed stimulation of bone resorption by endotoxin, confirming the role of LPS in the pathogenesis of periapical lesions seen by others4,10,32,52,59,67.

Considering the discussed above, the major objective of the dental professional during treatment of root canals of permanent teeth with pulp necrosis and chronic periapical lesion should not be only bacterial death, but also the inactivation of lipid A, which is the toxic portion of endotoxin. This objective is not reached by using root canal antibacterial dressings, which only kill the bacteria remaining in the root canal system after biomechanical preparation.

Medical and dental literature have published studies that have attempted to obtain a medication or substance that inactivates bacterial endotoxin, eliminating its biologically toxic potential. Caustic soda10,39, polymyxin B44, neutrophilic enzymes35, lysozyme41, formocresol50, 1.25% chlorhexidine1, and sodium hypochlorite6 have been tested, with no significant results. Many of these products present inherent limitations due to their high toxicity causing damaging effects when in contact with vital tissues. Thus, their routine clinical use is limited. The action of laser on periapical bacterial biofilm has also been tested2, however, its use is limited by the fact that there is no free access to the sites where the endotoxin is present, the root canal system of infected teeth, except when apical surgery is performed.



The first reference40 to the introduction of calcium hydroxide in dentistry was in 1838. However, its clinical use progressed only after the studies by Hermann16 in 1920. Calcium hydroxide, which has a highly alkaline pH, has been used in numerous different clinical situations, i.e., direct pulp protection, pulpotomy in permanent or deciduous teeth, root canal dressing in the treatment of permanent teeth with incomplete rhizogenesis, filling sealer in root canals, root perforations, dental resorptions, and antiseptic intracanal dressing56. This ample use has been attributed to its antibacterial activity12,29,30, biocompatibility15,17,38,54, hygroscopic property, ability to reduce periapical exudate16, and its capacity to induce mineralization28,54 and to dissolve necrotic tissue remnants after biomechanical preparation that can act as bacterial substrate14 leading to the stimulation of apical and periapical repair of teeth with chronic lesions.

Currently, one of the concerns of Endodontics is the treatment of teeth with pulp necrosis and periapical lesion because treatment failure is higher than in cases without periapical lesion. In teeth with chronic periapical lesion, there is a greater prevalence of Gram-negative anaerobic bacteria disseminated throughout the root canal system (dentinal tubules, apical craters and cementum lacunae), including apical bacterial biofilm. Because these areas are not reached by instrumentation, the use of an rootcanal dressing is recommended to aid in the elimination of these bacteria and increase the possibility of clinical success25,28,38,63.

According to Leonardo, et al.30, teeth with and without radiographically visible periapical lesion are different pathological entities requiring different treatment. In the first case, they recommend the use of an root canal dressing between treatment sessions, because the success of treatment in cases with a periapical lesion is directly related to the elimination of bacteria, products and subproducts from the root canal system. The procedures and medicaments used in root canal treatment should not only lead to bacterial death, but also to the inactivation of bacterial endotoxin.

Because of the lack of information concerning the effect of intracanal dressings on residual LPS that may adhere to mineralized tissues8, Safavi and Nichols48 evaluated in vitro the effect of calcium hydroxide on bacterial LPS. They concluded that calcium hydroxide hydrolyzes the highly toxic lipid A molecule that is responsible for the damaging effects of endotoxin. In a later study, Safavi and Nichols49 concluded that calcium hydroxide transforms lipid A into fatty acids and amino sugars which are atoxic components. These results were confirmed in recent studies by Barthel, et al.4 and Olsen, et al.42 who reported that calcium hydroxide detoxifies bacterial LPS in vitro.

In 2002, Nelson-Filho, et al.37 carried out an in vivo study to evaluate radiographically the effect of endotoxin plus calcium hydroxide on apical and periapical tissues of dog's teeth. They observed that the endotoxin caused the formation of periapical lesions after 30 days and that calcium hydroxide inactivated bacterial LPS. Silva, et al.55 analyzed histopathologically apical and periapical tissues of dog teeth in which the root canals were filled with bacterial LPS and calcium hydroxide. They reported that LPS caused the formation of periapical lesions and that calcium hydroxide detoxified this endotoxin in vivo.

More recently, Tanomaru, et al.61 evaluated the effect of biomechanical preparation using different irrigating solutions and a calcium hydroxide-based root canal dressing in dog teeth containing endotoxin. Biomechanical preparation with only irrigating solutions did not inactivate the endotoxin, however, the same treatment associated with the use of the calcium hydroxide root canal dressing (Calen®, SS White Artigos Dentários Ltda – RJ - Brasil) was effective in the inactivation of the toxic effects of this endotoxin. With the objective of evaluating the production of TNF-a, IL-1 and nitrite in cultures of human monocytes incubated with different concentrations of LPS and associated with the calcium hydroxide-based paste (Calen®) or pure calcium hydroxide, Zuccolotto68 showed that calcium hydroxide was capable of inactivating LPS.

Jiang, et al.23 also evaluated the direct effects of LPS on osteoclastogenesis and the capacity of calcium hydroxide to inhibit the formation of osteoclasts stimulated by endotoxin. They reported that calcium hydroxide significantly reduced osteoclast differentiation.

This new knowledge has revolutionized concepts about root canal dressings, indicating calcium hydroxide as not only the medicament most indicated, but fundamentally the only one currently capable of inactivating the endotoxin present in the root canal system of teeth with pulp necrosis and chronic periapical lesion.



- Bacterial endotoxin (LPS), which is a component of Gram-negative cell wall, is present in all teeth with pulp necrosis and radiographically visible chronic periapical lesion. It plays fundamental role in the genesis and maintenance of periapical lesions due to the induction of inflammation and bone resorption;

- Calcium hydroxide inactivates the toxic effects of bacterial endotoxin, in vitro and in vivo, and is currently the only clinically effective medicament for inactivation of endotoxin.



1- Aibel K, Stevens R. Effect of chlorhexidine on IL-6 induction by LPS. J Endod 1999; 25:282.        [ Links ]

2- Araki AT, Lage-Marques JL, Ibaraki Y, Kawakami K. Ação do laser de Er:YAG no biofilme bacteriano periapical. RPG 1998; 5: 319.        [ Links ]

3- Assed S, Ito IY, Leonardo MR, Silva LAB, Lopatin D. Anaerobic microorganisms in root canals of human teeth with chronic apical periodontitis detected by immunofluorescence. Endod Dent Traumatol 1996; 12:66-9.        [ Links ]

4- Barthel CR, Levin LG, Reisner HM, Trope M. TNF-alpha in monocytes after exposure to calcium hydroxide treated Escherichia coli LPS. Int Endod J 1997; 30: 155-9.        [ Links ]

5- Blix IJS, Helgeland K. LPS from Actinobacillus actinomycetemcomitans and production of nitric oxide in murine macrophages J774. Eur J Oral Sci 1998; 106: 576-81.        [ Links ]

6- Buttler TK, Crawford JJ. The detoxifying effect of varying concentrations of sodium hypochlorite on endotoxins. J Endod 1982; 8: 59-66.        [ Links ]

7- Cotran RS, Kumar V, Robbins SL. Robbins - patologia estrutural e funcional. Rio de Janeiro: Guanabara Koogan, 1991.        [ Links ]

8- Dahlén G, Magnusson BC, Moller A. Histological and histochemical study of the influence of lipopolysaccharide extracted from Fusobacterium nucleatum on the periapical tissues in the monkey Macaca fascicularis. Archs Oral Biol 1981; 26:591-8.        [ Links ]

9- Day AE, Langkamp HH, Bowen LL, Ascencio F, Agarwal S, Piesco NP. Signal transduction during LPS-mediated activation of pulp fibroblasts. J Dent Res 1998; 77:673.        [ Links ]

10- Dwyer TG, Torabinejad M. Radiographic and histologic evaluation of the effect of endotoxin on the periapical tissues of the cat. J Endod 1981; 7:31-5.        [ Links ]

11- Galanos C. Physical state and biological activity of lipopolysaccharides. Toxicity and immunogenicity of the lipid A component. Z Immun - Forsch Bd 1975; 149:214-29.        [ Links ]

12- Georgopoulou M, Kontakiotis E, Nakou M. In vitro evaluation of the effectiveness of calcium hydroxide and paramonochlorophenol on aerobic bacteria from the root canal. Endod Dent Traumatol 1993; 9:249-53.        [ Links ]

13- Hashioka K, Yamasaki M, Nakane A, Horiba N, Nakamura H. The relationship between clinical symptoms and anaerobic bacteria from infected root canals. J Endod 1992; 18:558-61.        [ Links ]

14- Hasselgren G, Olsson B, Cvek M. Effects of calcium hydroxide and sodium hypoclorite on the dissolution of necrotic porcine muscle. J Endod 1998; 14:125-7.        [ Links ]

15- Heithersay GS. Stimulation of root formation in incompletely developed pulpless teeth. Oral Surg 1970; 29:620-30.        [ Links ]

16- Hermann BW. Calcium hydroxide as mitted zin behandeen und fullen von wurzel. Diss. Wurzbrug., 1920 apud Leonardo MR, Leal JM. Endodontia: tratamento de canais radiculares. São Paulo: Panamericana, 1991:1-18.        [ Links ]

17- Holland R, Souza V. Tratamento conservador da polpa dental. In: Leonardo MR, Leal JM. Endodontia: tratamento de canais radiculares. São Paulo: Ed Médica Panamericana, 1998:63-75.        [ Links ]

18- Hook WA, Snyderman R, Mergenhagem SE. Histamine releasing factor generated by the interation of endotoxin with hamster serum. Infect Immun 1970; 2:462-7.        [ Links ]

19- Horiba N, Maekawa Y, Abe Y, Ito M, Matsumoto T, Nakamura H. Correlations between endotoxin and clinical symptoms or radiolucent areas in infected root canals. Oral Surg 1991; 71:492-5.        [ Links ]

20- Horiba N, Maekawa Y, Abe Y, Ito M, Matsumoto T, Nakamura H, Ozeki M. Cytotoxity against various cell lines of lipopolysaccharides purified from bacteroides, fusobacterium, and veillonella isolated from infected root canals. J Endod 1989; 15:530-4.        [ Links ]

21- Horiba N, Maekawa Y, Yamauchi Y, Ito M, Matsumoto T, Nakamura H. Complement activation by lipopolysaccharides purified from gram-negative bacteria isolated from infected root canals. Oral Surg 1992; 74:648-51.        [ Links ]

22- Ito HO, Shuto T, Takada H, Koga T, Aida Y, Hirata M, Koga T. Lipopolysaccharides from Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans promote osteoclastic differentiation in vitro. Archs Oral Biol 1996; 41:439-44.        [ Links ]

23- Jiang J, Zuo J, Chen SH, Holiday LS. Calcium hydroxide reduces lipopolysaccaride-stimulated osteoclast formation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003; 95:348-54.        [ Links ]

24- Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol 1965; 20:340-9.        [ Links ]

25- Katebzadeh N, Hupp J, Trope M. Histological periapical repair after obturation of infected root canals in dogs. J Endod 1999; 25:364-8.        [ Links ]

26- Könönen E, Kanervo A, Takala A, Asikainen S, Jousimies-Somer H. Establishment of oral anaerobes during first year of life. J Dent Res 1999; 78:1634-9.        [ Links ]

27- Kumada H, Haishima Y, Umemoto T, Tanamoto KI. Structural study on the free lipid A isolated from lipopolysaccharide of Porphyromonas gingivalis. J Bacteriol 1995; 177:2098-106.        [ Links ]

28- Leonardo MR, Silva LAB, Leonardo RT, Utrilla LS, Assed S. Histological evaluation of therapy using a calcium hydroxide dressing for teeth with incompletely formed apices and periapical lesions. J Endod 1993; 19:348-52.        [ Links ]

29- Leonardo MR, Silva LAB, Leonardo RT. Devemos usar medicação intracanal no tratamento de dentes com necrose pulpar? In: Odontologia Integrada – atualização multidisciplinar para o clínico e o especialista. Rio de Janeiro: Editora Pedro Primeiro Ltda, 1999. p.179-95.        [ Links ]

30- Leonardo MR, Silva LAB, Leonardo RT. Tratamento de canal radicular em sessão única: crença vs. ciência. In: Feller C, Gorab R. Atualização na Clínica Odontológica. São Paulo: Artes Médicas, 2000. p.29-57.        [ Links ]

31- Matsushita K, Tajima T, Tomita K, Takada H, Nagaoka S, Torii M. Inflammatory cytokine production and specific antibody responses to lipopolysaccharide from endodontopathic black-pigmented bacteria in patients with multilesional periapical periodontitis. J Endod 1999; 25:795-9.        [ Links ]

32- Mattison GD, Haddix JE, Kehoe JC, Progulske-Fox A. The effect of Eikenella corrodens endotoxin on periapical bone. J Endod 1987; 13:559-65.        [ Links ]

33- McGee JOD, Isaacson PG, Wright NA. Oxford textbook of pathology. Principles of pathology. Oxford: University Press, 1992.        [ Links ]

34- Morrison B, Kline L. Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J Immunol 1977; 118:362-8.        [ Links ]

35- Munford RS, Hall CL. Detoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme. Science 1986; 234:203-5.        [ Links ]

36- Nair BC, Mayberry WR, Dziak R, Chen PB, Levine MJ, Hausmann E. Biological effects of a purified lipopolysaccharides from Bacteroides gingivalis. J. Periodont Res 1983; 18:40-9.        [ Links ]

37- Nelson-Filho P, Leonardo ML, Silva LAB., Assed S. Radiografic evaluation of the effect of endotoxin (LPS) plus calcium hydroxide on apical and periapical tissues of dogs. J Endod 2002; 28:694-6.        [ Links ]

38- Nelson-Filho P, Silva LAB, Leonardo MR, Utrilla LS, Figueiredo F. Connective tissue response to calcium hydroxide – based root canal medicaments. Int Endodon J 1999; 32:303-11.        [ Links ]

39- Niwa M, Milner KC, Ribi E, Rudbach JA. Alteration of physical, chemical, and biological properties of endotoxin by treatment with mild alkali. J Bacteriol 1969; 97:1069-77.        [ Links ]

40- Nygreen JA Radgivare angaende basta sattet att varda och levara tandernas friskhet apud Martin DM, Crabb HSM. Calcium hydroxide in root canal therapy. A review. Br Dent J 1977; 142:277-83.        [ Links ]

41- Ohno N, Takada K, Kurasawa T, Liang A, Yadomae T. Detoxification of lipopolysaccharide by lysozyme. Endotoxin and sepsis: molecular mechanism of pathogenesis, host resistance, and therapy. Proceedings of the 4th Conference of the International Endotoxin Society, 1988: p. 170-90.        [ Links ]

42- Olsen MH, Difiore PM, Dixit SN, Veis A. The effects of calcium hydroxide inhibition on LPS induced release of IL-1b from human monocytes in whole blood. J Endod 1999; 25: 289.        [ Links ]

43- Pitts DL, Williams BL, Morton Jr TH. Investigation of role of endotoxin in periapical inflammation. J Endod 1982; 8: 10-8.        [ Links ]

44- Porro M, Rustici A, Velucchi M, Agnello D, Villa P, Guezzi P. Natural and synthetic polypeptides that recognize the conserved lipid A binding sites of lipopolysaccharides. Endotoxin and sepsis: molecular mechanism of pathogenesis, host resistance, and therapy. Proceedings of the 4th Conference of the International Endotoxin Society, 1998:316-25.        [ Links ]

45- Raetz CRH. Bacterial endotoxins: extraordinary lipids that activate eucaryotic signal transduction. J Bacteriol 1993; 75:5745-53.        [ Links ]

46- Rietschel ET, Brade H. Bacterial endotoxins. Scientific American 1992; 267:26-33.        [ Links ]

47- Rietschel ET, Kirikae T, Schade FU, Ulmer AJ, Holst O, Brade H, Schmidt G, Mamat U, Grimmecke HD, Kusumoto S, Zahringer U. The chemical structure of bacterial endotoxin in relation to bioactivity. Immunobiol 1993; 187:169-90.        [ Links ]

48- Safavi KE, Nichols FC. Effect of calcium hydroxide on bacterial lipopolysaccharide. J Endod 1993; 19:76-8.        [ Links ]

49- Safavi KE, Nichols FC. Alteration of biological properties of bacterial lipopolysaccharide by calcium hydroxide treatment. J Endod 1994; 20:127-9.        [ Links ]

50- Sant'anna AT, Ramalho LTO, Spolidório DMP. Efeito do formocresol sobre o LPS bacteriano em tecido subcutâneo de camundongos. [In: Anais da 16a Reunião Anual da Sociedade Brasileira de Pesquisa Odontológica, - SBPqO; 1999 set 8-11; Águas de São Pedro (SP). São Paulo: SBPqO; 1999. p.36        [ Links ]

51- Seltzer S, Farber PA. Microbiologic factors in endodontology. Oral Surg 1994; 78:634-45.        [ Links ]

52- Schein B, Schilder H. Endotoxin content in endodontically involved teeth. J Endod 1975; 1:19-21.        [ Links ]

53- Shonfeld SE, Greening AB, Glick DD, Frank AL, Simon JH, Herles SM. Endotoxin activity in periapical lesions. Oral Surg Oral Med Oral Pathol 1982; 53:82-7.        [ Links ]

54- Silva LAB. Rizogênese Incompleta - Efeitos de diferentes pastas à base de hidróxido de cálcio na complementação radicular e na reparação periapical em dentes de cães - estudo histológico. Araraquara; 1988 [Dissertação de Mestrado. Faculdade de Odontologia da Universidade Estadual Paulista]        [ Links ]

55- Silva LAB, Nelson-Filho P, Leonardo MR, Rossi MA, Pansani C.A. Effect of calcium hydroxide on bacterial endotoxin in vivo. J Endod 2002; 28:94-8.        [ Links ]

56- Silva LAB, Assed S, Nelson-Filho P. Proteção Direta da Polpa: como fazer e o que utilizar. In: Atualização na Clínica Odontológica, São Paulo: Artes Médicas; 2002 v.2, p. 267-88.        [ Links ]

57- Siqueira-Júnior JF, Rôças IN. PCR methodology as a valuable tool for identification of endodontic pathogens. J Dent 2003; 31:333-9.        [ Links ]

58- Soares JA. Avaliação microbiológica, histopatológica e histomicrobiológica de dentes de cães com reação periapical crônica induzida, após preparo biomecânico automizado e aplicação de curativos de demora à base de hidróxido de cálcio. Araraquara; 2003. [Tese de Doutorado - Faculdade de Odontologia da Universidade Estadual Paulista]        [ Links ]

59- Stashenko P. The role of immune cytokines in the pathogenesis of periapical lesions. Endod Dent Traumatol 1990; 6:89-96.        [ Links ]

60- Sundqvist G. Ecology of the root canal flora. J Endod 1992; 18: 427-30.        [ Links ]

61- Tanomaru JMG, Leonardo MR, Tanomaru-Filho M, Bonetti-Filho I, Silva LAB. Effect of different irrigation solutions and calcium hidroxide on bacterial LPS. Int Endod J 2003; 36:733-9.        [ Links ]

62- Torabinejad M, Eby WC, Naidorf IJ. Inflammatory and immunological aspects of the pathogenesis of human periapical lesions. J Endod 1985; 11:479-88.        [ Links ]

63- Trope M, Delano EO, Orstavik D. Endodontic treatment of teeth with apical periodontitis: single vs. multivisit treatment. J Endod 1999; 25:345-50.        [ Links ]

64- Wang CY, Stashenko P. Characterization of bone-resorbing activity in human periapical lesions. J Endod 1993; 19:107-11.        [ Links ]

65- Westphal O. Bacterial endotoxins. Int Archs Allergy Appl Immun 1975; 49: 1-43.        [ Links ]

66- Wolff S. Biological effects of bacterial endotoxins in man. J Infect Dis 1973; 128: S259-S269.        [ Links ]

67- Yamasaki M, Nakane A, Kumazawa M, Hashioka K, Horiba N, Nakamura H. Endotoxin and gram-negative bacteria in the rat periapical lesions. J Endod 1992: 501-4.        [ Links ]

68- Zuccolotto CEBG. Detecção de TNF-a, IL-1 e Nitrito produzidos em cultura de monócitos expostos à endotoxina (LPS), associada ou não ao hidróxido de cálcio. Ribeirão Preto; 2003. [Dissertação de Mestrado da Faculdade de Odontologia da Universidade de São Paulo.        [ Links ]



Correspondence to
Mário Roberto Leonardo
Rua Humaitá, 1680 - Araraquara - SP - Brasil
CEP – 14801-903 - Fone:16-9782-6855

Received: March 01, 2004 - Returned for modification: April 22, 2004 - Accepted: May 12, 2004

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