SRS 16-86 attenuation of ferroptosis and promotion of recovery in
diabetic nephropathy
Abstract
Diabetic nephropathy (DN) is a common complication of diabetes mellitus
and cell death is a key issue in DN. Ferroptosis is a recently
discovered type of iron-dependent cell death and different from other
kinds of cell death including apoptosis and necrosis. However,
ferroptosis has not been described in the context of DN. This study was
to explore the role of ferroptosis in the DN pathophysiology and to
explore the efficacy of ferroptosis inhibitor SRS 16-86 on DN. The STZ
injection was used to establish the DM and DN animal models. We detected
the levels of iron, reactive oxygen species, and ferroptosis-specific
markers in a rat DN model to investigate whether there was ferroptosis
in the process of DN. The hematoxylin-eosin staining, blood
biochemistry, urine biochemistry and the of function kidney were used to
evaluate the efficacy of ferroptosis inhibitor-SRS 16-86 in repairing
DN. We found that SRS 16-86 could improve the recovery of renal function
after DN by improving the antiferroptosis factors glutathione peroxidase
4, glutathione, and system Xc-light chain and could lower the lipid
peroxidation marker and 4-hydroxynonenal. SRS 16-86 treatment may
improve the structure of renal organization after DN. Inflammatory
cytokines-interleukin 1β and tumor necrosis factor α, and intercellular
adhesion molecule 1 were decreased significantly following SRS 16-86
treatment after DN. Results indicate that there is a strong connection
between ferroptosis and the pathological mechanism of DN. The validity
of SRS 16-86, a ferroptosis inhibitor in DN repair, supports its
potential as a new therapeutic target for DN.