Endotoxin, present on all Gram- negative bacteria, is consists of polysaccharides, lipids and proteins and is simply referred to as lipopolysaccharide( LPS), which already reflects its chemical structure.31,32 MOH Lipid A is the place of the endotoxin molecule responsible for its toxic outcome. When endotoxins are free, they do not cause cell or tissue pathosis, but instead induce competent cells to launch chemical mediators.33 MOH Macrophages are the primary goal of endotoxins.33 consequently Endotoxins are not intrinsically toxic. Throughout root canal treatment, LPS is released during proliferation or bacterial death, triggering a series of biological effects34 that lead to an inflammatory response32 and periapical bone resorption.35,36 MOH At present, one of the concerns of endodontics is the treatment of teeth with necrotic pulps and periapical disease, as treatment failures in such cases are greater than in cases without periapical disease37,38. MOH In teeth with chronic periapical lesions, there are more prominent predominance of Gram- negative anaerobic bacteria distributed throughout the root canal system( dentine tubules, apical resorptive defects and cement lacunae), including apical bacterial biofilm. 37- 40MOH Since these areas cannot be cleaned or managed by instrumentation, the use of a root canal medicaments is proposed to help reducce these bacteria and increase the likelihood of clinical success.37- 39 MOH
Teeth with and without radiographically noticeable periapical lesions can be categorized as different pathological conditions requiring different treatment plans. If bone destruction has occurred, some suggested the usage of a root canal medicaments between treatment sessions, 41 MOH since the achievement of a successful treatment for periapical pathosis is directly linked to the removal of bacteria from the root canal system. The procedures and medicaments utilized in root canal treatment should not only result in the death of bacteria, but should also lead to the inactivation of bacterial endotoxin.33 MOH

An in vitro study shows that Ca( OH) 2 hydrolyzed the highly toxic molecule of lipid A, directly responsible for the harmful effects of endotoxin42. Another study revealed that Ca(OH)2 converted lipid A into fatty acids and amino sugars that are non- toxic compounds.43 These results have been verified by other in vitro studies.34,44MOH

In two in vivo studies Nelson- Filho et al.39 and Silva et al.45 clearly showed that endotoxin triggers the development of periapical lesions and Ca( OH) 2 serve to inactivate bactrial LPS. In a study applied on dog teeth, Tanomaru et al.46 indicated that a biomechanical preparation containing only irrigating solutions did not inactivate the endotoxin, but the same protocol of treatment associated with the use of the Ca(OH)2 dressing was effective enogh to inactivate the harmful effects of this endotoxin. Another study showed that Ca(OH)2 significantly decreased osteoclast differentiation.47 It was exhibited that long- term application of Ca(OH)2 detoxified LPS molecules by hydrolysis of ester bonds in the fatty acid chains of the lipid A moiety( Table 2) .48MOH