A novel Si-based antioxidant agent attenuates antibody-mediated rejection in allogeneic rat kidney transplantation

Abstract

Antibody-mediated rejection remains a leading cause of graft loss during kidney transplantation. Ischemia reperfusion injury (IRI) has been reported to promote T cell proliferation, leading to B cell activation and subsequent production of donor-specific antibodies, which target antigens on the vascular endothelium. We hypothesize that a novel therapeutic strategy targeting highly toxic reactive oxygen species could mitigate oxidative stress and immune responses associated with IRI. Our previous study demonstrated that oral administration of a silicon (Si)-based agent consistently generates substantial amounts of hydrogen, effectively suppressing IRI-induced oxidative stress and acute kidney injury in a rat renal clamp model. Here, we investigated the effect of the Si-based agent on immune responses in an allogeneic kidney transplant setting. Using both short-term and long-term evaluation models, we found that the Si-based agent suppressed oxidative stress and acquired immunity activation. Furthermore, early suppression of donor-specific antibody production and amelioration of chronic antibody-mediated rejection were observed. These findings indicate that the Si-based agent offers protective effects on graft function and survival, highlighting its potential clinical application to improve outcomes for kidney transplant recipients.

Keywords: donor-specific antibody; kidney transplantation; oxidative stress; rat; rejection; silicon.