A nickel implant induces cell death through autophagy in the connective tissue capsule in an experimental model

Abstract

Aim: To identify cellular autophagy markers around nickel-containing implant as evidence of metal hypersensitivity reactions in an animal model. Materials and Methods: Rats were sensitized to nickel using a modified model involving the administration of NiSO4 with adjuvants. Subsequently, nickel plate implants (Ni content at 98.9%) were placed subfascially in the rats. Five months after implantation, the capsule morphology and autophagy were examined through the immunohistochemical detection of Beclin1 and GRP78. Implants tissue capsules without previous NiSO4 exposition were considered as control. Results: A high immunoreactions to GRP78 were observed in the implant capsule wall, with Beclin1-positive cells primarily noted at the interface with the implant. GRP78 and Beclin1 were significantly higher (p=0.01) expressed in cases with adjuvants, serving as a model for provoking an acute tissue response to implant. Conclusions: In addition to inflammation and necrosis, cell death in the connective tissue capsule wall occurs through autophagy. Autophagy, mediated by Beclin1, is prominent at the implant interface and is closely associated with GRP78, which is strongly expressed throughout the capsule thickness, indicating significant oxidative stress in the cells surrounding the nickel plate implant.