##SRS 16-86 downregulated the expression of ROS and
4-hydroxynonenal level in DN
Ferroptosis is caused by the
lipid peroxidation induced by ROS accumulation: ROS decomposition
produces malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which then
form covalent adjuncts with proteins, DNA, lipids, and other
macromolecules to cross-link and inactivate proteins that promote
ferroptosis, thus precipitating cell membrane rupture and ferroptosis.
In this study, we detected the ROS (Figure 3B) and 4HNE (Figure 4A,4D)
expressions. 4HNE and ROS levels were significantly upregulated post-DN
in the DN group compared to the control group. After treatment with SRS
16-86, 4HNE and ROS expression was upregulated, demonstrating that SRS
16-86 could inhibit lipid peroxidation.
##SRS 16-86 upregulated thelevel of xCT, GSH, and GPX4
in DN
The xCT-GSH-GPX4 axis contributed to the negative regulation of
ferroptoptic-related cell death. High extracellular glutamate levels can
inhibit systemic xCT activity and thus induce ferroptosis. We detected
the expression of xCT, GPX4, and GSH post-DN (Figure 4A,4B,4C,4E). xCT,
GPX4, and GSH levels were significantly reduced post-DN in the DN group
compared to the control group. These results indicated that the capacity
of peroxidation repair in the kidneys of diabetic rats was dramatically
reduced. We also found that the expression of xCT, GPX4, and GSH were
upregulated after treatment with SRS 16-86. The antioxidant capacity was
repaired in the SRS group.