Cytotoxicity and Genotoxicity of a New Intracanal Medicament, 2-hydroxyisocaproic Acid-An In Vitro Study.

A successful outcome of root canal therapy relies on effective disinfection of the root canal system, including the use of intracanal medicaments, which vary in their bactericidal and cytotoxic properties. Assessing the benefits and risks associated with the use of these medicaments is of extreme importance, especially in regenerative endodontic procedures, because residual stem cells may be harmed. In this study, we tested the cytotoxicity and genotoxicity of a novel agent, 2-hydroxyisocaproic acid (HICA), and compared its properties with those of a well-established medicament, calcium hydroxide. Human periodontal ligament fibroblasts were exposed to varying concentrations of HICA (1, 2.5, 5, 10, 20, and 40 mg/mL) for 24 hours, and a dose-response curve was generated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Immunofluorescence for 2 markers of DNA double-strand breaks, phosphorylated γH2AX and 53BP1, was used to establish the genotoxicity of HICA at various half maximal effective concentration (EC50) fractions. Cytotoxicity and genotoxicity of HICA and calcium hydroxide at 1 mg/mL were compared at 24 and 48 hours using the same methods. At 10 mg/mL and higher, HICA was significantly more cytotoxic and genotoxic than the control (P < .05 and P < .0001, respectively). Calcium hydroxide at 1 mg/mL was more cytotoxic than HICA at 1 mg/mL at 24 and 48 hours (P < .05 for both), whereas no difference in the accumulated DNA damage was observed. HICA is not cytotoxic and genotoxic at concentrations <10 mg/mL. At the concentration of 1 mg/mL, HICA is significantly less cytotoxic than calcium hydroxide.

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