Date of Publication: 14-Jun-2022
Effects of pre-ischemic prolyl-hydroxylase inhibitor on long-term renal functions in rats
Author: Gaaminepreet Singh, Rimpi Arora, Pawan Krishan
Background: Ischemia leads to acute kidney injury (AKI) and associated with adverse hospital outcomes. It is known that AKI resolves in few days, but the progressive kidney disease does not halt. Induction of ischemia-reperfusion (I/R) injury results in oxygen metabolism defects resulting in hypoxia, which activates fibrogenic responses. The hypoxia inducible factors (HIFs) system comprising of HIF-1__ampersandsignalpha; and HIF-1__ampersandsignbeta; subunits is degraded by prolyl-hydroxylase (PHD) enzyme. Several evidences have suggested that inhibition of HIFs degradation prevents renal I/R induced AKI in rodents. However, the effects of HIF pre-induction on renal I/R induced chronic kidney disease (CKD) in rodents has not been investigated. Materials and Methods: Bilateral renal I/R injury was performed by clamping both renal pedicels for 45 min. Modulation of HIFs was done by administering PHD inhibitor cobaltous chloride prior to I/R. CKD was evaluated by proteinuria, oxidative stress, HIF-1__ampersandsignalpha; protein levels and histological studies. Results: Renal I/R injury induced AKI as indicated by elevated serum creatinine levels post 1 day. Various CKD features such as proteinuria, reduced catalase activity, glomerular hypertrophy, glomerulosclerosis, fibrosis were evidenced 90 days post I/R injury. Pre-treatment with PHD inhibitor reduced the incidence of AKI in I/R rats. Besides up-regulation of renal HIF-1__ampersandsignalpha; protein levels after 90 days, development of CKD was not retarded in pre-treated I/R rats. Conclusion: Thus, we conclude that early HIF modulation is insufficient in attenuating I/R induced CKD in rats.
Keywords: Gaaminepreet Singh, Rimpi Arora, Pawan Krishan
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