Determination of time-dependent changes in the levels of selected mİRNAs associated with cell death induced by renal ischemia-reperfusion injury

It has been determined that more than one cell death mechanism works due to the severe damage to the tissues during the ischemia/reperfusion (I/R) process. One of these types of cell death is ferroptosis. Today, studies show that various microRNAs play a role in regulating the ferroptosis process, the mechanism of which is still being studied. In our study, using Sprague Dawley male albino rats, 30, 45, and 60 minutes of ischemia followed by 24 hours of reperfusion were applied to the left kidney. In the sham group, only surgical stress was applied. At the end of 24 hours, kidney tissue and blood samples were collected from the experimental groups who were euthanized under anesthesia. Serum and tissue iron levels, total oxidative and antioxidative species in serum were examined spectrophotometrically. The mRNA expression levels of SLC40A1, NCOA4, SLC39A8, and GPX4 genes that play a role in the development of ferroptosis and five different miRNAs (rno-miR-1839-5p, rno-miR-105, rno-miR-879-5p, rno- miRNAs) associated with these selected genes. miR-6332 and rno-miR-409b) expression levels were investigated by the RT-qPCR method. In the I/R groups, an increase in total oxidative species and a decrease in total oxidative and antioxidative species were observed in serum levels compared to sham groups. In addition, a significant increase in iron levels was observed in both tissue and serum samples. GPX4 and SLC40A1 mRNA expression in all I/R groups; SLC39A8 mRNA expression decreased significantly in the 45 and 60-minute I/R groups. It was observed that NCOA4 mRNA expression level was significantly increased in all groups. While a significant increase was observed in the expression levels of rno-miR-105, rno-miR-6332 and rno-miR-409b, a significant decrease was observed in the expression of rno-miR-879- 5p compared to the sham group. A significant decrease in rno-miR-1839-5p was detected only in the 45-minute ischemia group compared to the sham group. In this study, timedependent changes in the expression levels of 5 selected miRNAs associated with ferroptosis cell death induced by renal I/R injury were investigated for the first time.