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Another point that emerged in this work was the involvement of the peripheral macrophages in the inflammatory process of the CDDP-induced oral mucosa alterations.

One possible mechanism is that the characteristic genomic damage associated with this drug can lead to the expression of macrophage activation markers \[[@B17]\]. Additionally, the systemic inflammatory response observed in these animals was related to macrophages, and they were also observed in the granulation tissue of the gingiva mucosa \[[@B18]\].

Systemic exposure to CDDP induced a significant increase of mRNA expression of TNF-*α*, and IL-6 in animals of the NC group. These levels were reduced in the CDDP group, and the presence of paw edema was not related to the reduction of the expression of these cytokines in this experimental model. *Il-6* is a cytokine with a key role in inflammation, and it is highly expressed in gingival mucosa after the chronic administration of CDDP \[[@B11]\]. Besides, the activation of macrophages and neutrophils was also observed in the gingival mucosa after the systemic treatment with the drug \[[@B11], [@B19]\].

One limitation of the study was the study design. Other experimental protocols were not evaluated, which could have provided more information about the process of CDDP-induced oral mucosa alterations and its immunological alterations.

5. Conclusions {#sec5}
==============

The chronic subcutaneous administration of CDDP causes the appearance of gingivitis in BALB/c mice. There was also a reduction of the expression of mRNA of *Il-1*β, *Tgf-α,* and *Il-6* in the gingival tissue of animals submitted to CDDP. There was no influence of the local and systemic inflammatory response in the presence of gingivitis.

The authors would like to thank all the technical staff at the Animal
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