Abstract
BackgroundHyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI.MethodsTwenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed.ResultsOur results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis.ConclusionOur results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.
Highlights
Acute kidney injury (AKI) is a multiphasic clinical syndrome characterized by a rapid decline in renal function
Our results demonstrated that HHcy could exacerbate ischemia-reperfusion injury (IRI)-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, Jun N-terminal kinase (JNK) pathway activation, and consequent apoptosis
Our results suggest that preexisted HHcy condition can promote the activation of the JNK pathway caused by IRI
Summary
Acute kidney injury (AKI) is a multiphasic clinical syndrome characterized by a rapid decline in renal function. Many factors such as ischemia/reperfusion [1], sepsis [2], trauma [3], and contrast [4] can induce the development of AKI. Hyperhomocysteinemia (HHcy), defined as blood Hcy concentration >15 μmol/L, is mainly developed by dysfunction of enzymes and cofactors associated with the biosynthesis and metabolism of Hcy. Hyperhomocysteinemia (HHcy), defined as blood Hcy concentration >15 μmol/L, is mainly developed by dysfunction of enzymes and cofactors associated with the biosynthesis and metabolism of Hcy Other factors such as excessive methionine intake and certain diseases can induce the development of HHcy [7].
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