Ischemic postconditioning prevents renal ischemia reperfusion injury through the induction of heat shock proteins in rats

Abstract

Ischemic postconditioning (IPo) attenuates ischemia-reperfusion injuries (IRI) in various organs, of both animals and humans. This study tested the hypothesis that IPo attenuates renal IRI through the upregulation of heat shock protein (HSP)70, HSP27 and heme oxygenase-1 (HO-1, also known as HSP 32) expression. Adult Sprague Dawley rats were subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h. One group of rats received IPo prior to restoring full perfusion. Another group was administered 100 mg/kg HSP inhibitor quercetin, injected intraperitoneally 1 h prior to ischemia. Control rats received sham operations. Renal IR resulted in severe morphological and pathological changes, with increased serum creatinine and blood urea nitrogen concentrations. IR resulted in increased inflammation by inducing plasma tumor necrosis factor-α and renal nuclear factor kappa-light-chain-enhancer of activated B cells expression. IR also increased lipid peroxidation, as indicated by elevated malondialdehyde content, reduced superoxide dismutase activity and increased renal apoptosis. Renal HSP70, HSP27 and HO-1 mRNA and protein levels were increased by IR and further elevated by IPo. IPo attenuated these changes observed in pathology, lipid peroxidation, apoptosis and inflammation. Quercetin treatment abolished all the protective effects of IPo. In conclusion, this study showed that IPo can attenuate lipid peroxidation, apoptosis and inflammation as well as renal IRI by upregulating the expression of HSP70, HSP27 and HO-1.

Heme Oxygenase-1 in Kidney Health and Disease

“…Guo et al subjected rats to a bilateral 45-min IRI and showed that the beneficial effect of IPo was due to upregulation of heat shock proteins (HSPs), including HO-1 (49). As expected, IR rats demonstrated severe kidney damage and impaired renal function.…”

“…There was increased lipid peroxidation, inflammation, and tubular epithelial apoptosis in the kidneys of the IR rats and these were markedly reduced in the IPo group after IRI. Quercetin, a nonspecific HSP inhibitor, significantly repressed the renoprotective effects of IPo (49). In addition, remote ischemic preconditioning has demonstrated HO-1-mediated cardioprotection (160, 161) and improved outcomes in liver IRI (62,143).…”

Molecular Mechanisms of Renal Ischemic Conditioning Strategies

“…Nonetheless, increased levels of adenosine [103], phosphorylated Akt and ERK1/2 [57] and MAPK-activating protein kinase-2 were found [104]. The mediators and end effectors of IPoC include phosphorylated HSP27 [104,105], HSP70 [105], PKC and NO [15]. An IPoC-induced decreased level of phosphorylated JNK has also been reported [48].…”

“…Regarding anti-inflammatory effects, IPoC has been shown to significantly downregulate pro-inflammatory mediators after renal IR, such as TNF-α in renal tissue [71,113] and plasma [105,113], IL-6 [114], IL-1β [71,114] and ICAM-1 [71] as well as to inhibit NF-κB in renal tissue [105] (fig. 1).…”

“…IPoC ensures mitochondrial integrity and intact mitochondrial permeability, thereby avoiding cytochrome c release to the cytosol and activation of pro-apoptotic pathways. IPoC downregulates Bax, PARP, caspase-3 and caspase-12 [48,57,71,105,108]. An increase in the anti-apoptotic mediator, Bcl-2, has been detected as well following IPoC [57,108].…”