Effects of Remote Ischemic Postconditioning Treatment on Ferroptosis and Hexokinase II Levels in a Rat Model of Cerebral Ischemia-Reperfusion Injury

Annals of Medical Research, cilt.33, sa.7, ss.312-317, 2026 (TRDizin)

Aim: Cerebral ischemia-reperfusion (I/R) injury is an unavoidable outcome of reperfusion ther-

apy following a stroke, initiating intricate death mechanisms at both cellular and molecular lev-

els. Comprehending the molecular pathways that result in neuronal death post-stroke is crucial

for the development of effective neuroprotective strategies. Ferroptosis is a mechanism of cell

death characterized by iron-dependent lipid peroxidation and is believed to contribute to the

damage associated with cerebral I/R injury.

Materials and Methods: Thirty male Sprague-Dawley rats were randomly assigned to three ex-

perimental groups: Control, IR, and IR+REPOSTC (n=10). Cerebral ischemia was induced using

the intraluminal filament technique for 60 minutes, and the animals were euthanized after a

24-hour reperfusion period. The femoral artery of the right hind limb of the rat underwent Re-

PostC consisting of three cycles of 5 minutes of ischemia followed by 5 minutes of reperfusion.

Triphenyl tetrazolium chloride (TTC) staining was used to measure infarct size.

Results: Compared to the control group, the I/R group showed a significant increase in glu-

tathione peroxidase 4 (GPX4) levels, while RePostC treatment significantly decreased GPX4 lev-

els. Compared to the control group, the I/R group showed a significant decrease in hexokinase II

(HKII) levels. The RePostC group, however, exhibited a substantial increase in these levels com-

pared with the I/R group. Levels of arachidonic acid 12-lipoxygenase (ALOX12) and lipocalin 2

(LCN2) were significantly increased in the I/R group compared with the control group. No sta-

tistically significant difference was observed between the RePostC treatment group and the I/R

group.

Conclusion: Ferroptotic cell death plays a role in the damage that occurs after cerebral I/R.

GPX4, ALOX12, LCN2, and HKII levels may serve as potential targets for the management of

cerebral ischemia-reperfusion injury. The RePostC application may help protect against I/R in-

jury by activating the body's own tolerance mechanisms.