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

Abstract

In this study, we investigated the impact of endogenous hydrogen sulfide (H 2 S) 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-kB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1b, IL-6, IL-18 and TNF-a (p50.05), and exhibited acute kidney injury (p50.05) and apoptosis (p50.05). Compared to the IR group, rats receiving PAG or HA showed significantly higher levels of TLR-2, TLR-4, nuclear NF-kB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1b, IL-6, IL-18 and TNF-a (p50.01), more severe acute kidney injury (p50.05) and increased apoptosis (p50.01). Thus, inflammatory response and apoptosis mediated by TLRs are involved in renal IRI. Inhibition of endogenous H 2 S significantly activated inflammatory response and apoptosis, and thus promoted renal IRI.

Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats

“…5 . This finding is in line with previous studies 32 33 34 35 36 37 which showed that upregulation of expression of cytokines or activation of NF-κB in glomeruli, renal tubules, and the peritubular interstitium were detected during the acute kidney injury induced by ischemia reperfusion injury. These suggest that interstitial cells (such as morphologies, resident leukocytes/monocytes) may also play an important role in the acute kidney injury, which deserved further study.…”

Hydrogen Sulfide Attenuates LPS‐Induced Acute Kidney Injury by Inhibiting Inflammation and Oxidative Stress

“…Shibuya et al [ 15 ] demonstrated that H 2 S suppressed high glucose-induced cardiomyocyte inflammation by inhibiting the TLR4/NF- κ B pathway and NLRP3 activation. Moreover, Tan et al [ 35 ] also identified the protective effect of endogenous H 2 S on renal IRI by suppressing inflammatory response through the inhibition of the TLR pathway. Zhang et al [ 19 ] demonstrated that H 2 S could attenuate LPS-induced acute lung injury by reducing oxidative stress and inhibiting inflammation.…”

Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the hepatobiliary tract disease

“…DNA fragmentation, an apoptotic marker, within cells fixed in the thin sections of liver was detected in situ (TACS•XL DAB In Situ Apoptosis Detection Kit, Trevigen Inc., Gaithersburg, MD). Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)-positive cells were counted under high power microscopy on 10 non-overlapping areas in each case and are presented as percent positive cells per total number of cells counted in the field [ 70 ].…”