Hepatic cytoprotection by nitric oxide and the cGMP pathway after ischaemia–reperfusion in the rat

Poly-ADP-Ribose-Polymerase Inhibition Ameliorates Hind Limb Ischemia Reperfusion Injury in a Murine Model of Type 2 Diabetes

“…IL-6 has also been shown to be upregulated in patients with PAD, claudication 44–46 , and in those undergoing vascular bypass procedures 47 . There is literature to suggest that IL-6 can provide cytoprotection against various forms of acute tissue injury 48–50 , thus the finding that PJ34 did not reduce skeletal muscle levels of this cytokine might not be a sign of a failed therapeutic intervention.…”

Role of nitric oxide in hepatic ischemia-reperfusion injury

“…The authors postulated that iNOSinduced hepatic damage was via significant production of ROS [33] . We summarize some key studies investigating endogenous NO and NOS in hepatic IRI in Table 1 [3,21,25,[31][32][33][34][35][36][37] .…”

“…Aminoguanidine, 5 min before ischemia 120 NO derived from iNOS, antioxidant [25] Dogs FK 409, 30 min before ischemia and15 min before and 45 min after reperfusion 60 NO, improves hepatic microcirculation [34] Rats L-arginine, 7 d before IRI 60 NO, antioxidant [35] Rats L-NAME 60 min before ischemia 30 NO, antioxidant [3] Mouse Gadolinium chloride 24 h before ischemia 45 NO derived from eNOS, antioxidant, suppresses Kupffer cell function, regulated basal hepatic blood flow, but did not affect blood flow after reperfusion, attenuated neutrophils infiltration [21] L-NAME methyl ester 15 min prior to ischemia Rats L-arginine or Sodium nitroprusside or L-Name prior to ischemia 60 NO, improves peripheral liver blood flow after reperfusion, cytoprotective [36] Male rats Arginine or L-NAME or 8-bromo guanosine 3′ 5′-cyclic monophosphate or rat atrial natriuretic peptide (ANP 1-28) 30 min before ischemia 45 NO, antioxidant, antiproinflammatory cytokines, improves microcirculation by the cGMP pathway, inhibits neutrophil infiltration and platelet aggregation [37] Male rats IRI group: had partial clamping of portal vein and hepatic artery 90 iNOS expression peaked at 3 h and diminished at 24 h post reperfusion in IRI and ONO-1714 groups [31] ONO-1714 group: as above plus ONO-1714 just prior to reperfusion and 6 h thereafter ONO-1714 significantly inhibited plasma nitrates at 24 h post reperfusion Control group: sham operation ONO-1714 significantly inhibited plasma ALT at 12 h post reperfusion, together with inhibiting histological damage and peroxynitrate expression in liver Male rats Microvessel clamping of portal vein and left hepatic artery L-NAME and AE-ITU given to each of 6 rats exposed to microvessel clamping (time unknown) 60 L-NAME worsened, elevated levels of ALT/AST in IRI groups [32] AE-ITU mildly and significantly decreased levels of AST…”

Hepatic dysfunction after shock: Clinical parameters and biological pathways for therapeutic intervention

“…Nitrite formed by oxidation of NO may be cytoprotective in hypoxia as it can be reduced to NO. NO donors or 8-Brcyclic guanosine monophosphate can prevent cell death by activating guanyl cyclase without blocking IL-6 (77,78). Therefore it may be the level of NO present or the immediate cellular milieu that determines whether NO has pro-apoptotic or pro-survival results overall.…”