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This randomized controlled clinical trial evaluates the effect of conventional metronidazole and nano-formulated metronidazole as root canal irrigants, with and without ultrasonic activation, in patients with necrotic single-rooted teeth associated with apical periodontitis. A total of 60 participants will be randomly allocated into six equal groups according to the irrigant used and whether ultrasonic activation is performed. Sodium hypochlorite will be used as the conventional control irrigant. The study will compare the groups regarding post-operative pain and reduction in root canal endotoxin levels. Post-operative pain will be assessed using a Visual Analogue Scale, while endotoxin levels will be measured before and after treatment using an ELISA assay
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