Cystathionine γ-Lyase Is Involved in the Renoprotective Effect of Brief and Repeated Ischemic Postconditioning After Renal Ischemia/Reperfusion Injury in Diabetes Mellitus.

BACKGROUND:The aim of this study was to determine whether the protective effects of brief and repeated ischemic postconditioning (IPoC) are associated with the modulation of cystathionine γ-lyase (CSE) expression after renal ischemia/reperfusion (I/R) injury in diabetes mellitus (DM). METHODS:We subjected diabetic rats to 45 minutes of ischemia followed by reperfusion at 24 hours. Before reperfusion, diabetic rats were treated with 3 cycles of 6 seconds of reperfusion, followed by 6 seconds of ischemia. DL-Propargylglycine (PAG, a CSE inhibitor) was administered to the diabetic rats to investigate its effects on the severity of renal I/R injury in diabetes mellitus (DM). Blood samples and left kidneys were collected for the measurement of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and renal pathologic changes. Western blot and immunochemistry techniques were also performed for the localization of CSE. Levels of superoxidase dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis-alpha (TNF-α), and hydrogen sulfide (H₂S) were quantified using commercially available kits. RESULTS:The results showed that BUN and SCr levels increased on renal ischemia/reperfusion injury (RI/RI) in the DM group. Diabetic rats treated with IPoC exhibited significantly less renal damage on I/R. Kit measurements showed that IPoC could markedly inhibit the levels of MDA and TNF-α and also improve SOD and H₂S levels. Western blot and immunochemistry showed that expression of CSE was downregulated on I/R in the DM group and IPoC upregulated CSE expression, whereas PAG treatment resulted in opposite effects. CONCLUSION:Our findings show that brief and repeated IPoC increased the expression of CSE after I/R in DM, and the modulation of CSE may underlie the renoprotective effect of IPoC.

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