Correlation between REDOX enzymes and NET markers expression during the development of periapical lesions in mice

To evaluate and correlate the expression of REDOX enzymes and NET markers during the development of periapical lesions (PLs) in mice.

PLs were experimentally induced by pulpal exposure of first molars. In all, 42 mice were involved in a negative control and five periods (after 2, 5, 7, 21 and 42 days) (n = 7 in each period). Microscopic analysis of the specimens was carried out, considering inflammatory response and the PL area (mm²). In addition, qRT-PCR (genes) and immunohistochemistry assay (proteins) were performed for REDOX enzymes (NOS2, SOD1, CAT, and GSR) and NET markers (MPO, H3CIT, and ELANE). The significance level was set at 5%.

Pulpal exposure led to the formation of PLs, especially after 21 and 42 days, when there was significantly increased bone resorption compared to previous periods (P < 0.001). There was an increased expression of all REDOX enzymes, as well as MPO and H3CIT markers after pulpal exposure in at least one time point in relation to the negative control, especially after 5 days (P = 0.002 or less). NOS2, SOD1, ELANE and H3CIT were significantly correlated with the PL area (P < 0.05). In addition, there was also a correlation between REDOX enzymes and NET markers (P < 0.05), such as all REDOX enzymes with H3CIT, CAT and GSR with MPO, and CAT and GSR with ELANE (P < 0.05).

Pulpal exposure modified the expression of REDOX enzymes and NET markers throughout the development of PLs, as well as some of these enzymes and markers were correlated, which may suggest the association of different molecular pathways.

The association between REDOX activity and NETs, including their molecular signaling, may modify the development of PLs after pulpal exposure and should be investigated as a possible therapeutic target in periapical bone repair.