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3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis
Xun-Feng Zou1, Shao-Hua Wu2, Jian-Gong Ma3
1Department of General Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.
Background:
The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney.
Methods:
Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses.
Results:
OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells.
Conclusion:
Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.
Insights
3-O-methyl-D-glucose (OMG) protects kidneys during cold storage by inhibiting ferroptosis, reducing cellular damage, and improving transplant survival. This suggests OMG
Area of Science:
- Organ preservation
- Cryoprotective agents
- Renal transplantation
Background:
- 3-O-methyl-D-glucose (OMG) is a known cryoprotectant for cells.
- Its role in organ preservation during static cold storage (CS) is not understood.
- Investigating OMG's effect on kidney ischemia damage during cold preservation.
Purpose of the Study:
- To evaluate the protective effect of 3-O-methyl-D-glucose (OMG) on donor kidney cold preservation.
- To elucidate the mechanism of OMG's action in mitigating ischemia-reperfusion injury.
Main Methods:
- Rat kidney model with isolated cold storage and subsequent transplantation (KTx).
- Assessed cellular damage via lactate dehydrogenase (LDH) and apoptosis markers.
- Measured iron levels, malondialdehyde (MDA), mitochondrial damage, and inflammatory markers post-KTx.
Main Results:
- OMG pretreatment reduced LDH activity and tubular apoptosis in cold-stored kidneys.
- OMG partially inhibited ferroptosis, indicated by reduced iron and MDA levels.
- OMG improved renal function and prolonged 7-day survival post-KTx, decreasing inflammation.
Conclusions:
- 3-O-methyl-D-glucose (OMG) protects kidneys from prolonged cold ischemia by inhibiting ferroptosis.
- OMG demonstrates potential for clinical application in donor kidney preservation.
