Impact of endogenous hydrogen sulfide on toll-like receptor pathway in renal ischemia/reperfusion injury in rats.

In this study, we investigated the impact of endogenous hydrogen sulfide (H2S) on toll-like receptors (TLRs)-mediated inflammatory response and apoptosis in renal ischemia-reperfusion injury (IRI). Twenty-four male Wistar rats were randomly divided into four groups: sham, IR, IR + propargylglycine (PAG) and IR + hydroxylamine (HA). After right nephrectomy, rats were given saline for the sham and IR group, PAG for the IR + PAG group and HA for the IR + HA group, through the left renal artery for 20 min. Five minutes after drug administration, all rats except sham underwent 45 min of left renal ischemia followed by 24 h of reperfusion. Kidneys were harvested for histological and biochemical evaluation. Levels of TLRs, downstream signaling molecules and pro-inflammatory cytokines were determined by Western blot or immunohistochemistry. Hematoxylin and eosin (H&E) stained renal sections were used for histological grading of renal injury. Apoptotic cells were detected by TUNEL assay. Compared to the sham group, rats in the IR group showed higher renal levels of TLR-2, TLR-4, nuclear NF-κB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1β, IL-6, IL-18 and TNF-α (p < 0.05), and exhibited acute kidney injury (p < 0.05) and apoptosis (p < 0.05). Compared to the IR group, rats receiving PAG or HA showed significantly higher levels of TLR-2, TLR-4, nuclear NF-κB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1β, IL-6, IL-18 and TNF-α (p < 0.01), more severe acute kidney injury (p < 0.05) and increased apoptosis (p < 0.01). Thus, inflammatory response and apoptosis mediated by TLRs are involved in renal IRI. Inhibition of endogenous H2S significantly activated inflammatory response and apoptosis, and thus promoted renal IRI.