Hepatic ischemia-reperfusion injury is a major complication of liver transplantation, trauma, and shock. This pathological condition can lead to graft dysfunction and rejection in the field of liver transplantation and clinical hepatic dysfunction with increased mortality. Although the pathological mechanisms of hepatic ischemia-reperfusion injury are very complex, and several intermediators and cells are involved in this phenomenon, oxidative stress and inflammatory responses are the key processes that aggravate hepatic injury. This review summarizes the current understanding of oxidative stress and inflammatory responses and, in that respect, addresses the therapeutic approaches to attenuate hepatic ischemia-reperfusion injury.

The contributions of superoxide and nitric oxide to ischemia/reperfusion (I/R)‑induced neuropathic pain have previously been demonstrated in an animal model that mimics the symptoms of complex regional pain syndrome type I (CRPS I). Targeting peroxynitrite, which is the product of their interaction, may provide effective treatments for I/R‑induced neuropathic pain. In this study, the effect of the peroxynitrite decomposition catalyst FeTMPyP [5,10,15,20‑tetrakis (N‑methyl‑4'‑pyridyl)porphyrinato iron (III)], administered at doses of 1, 3 and 10 mg/kg via intraperitoneal injection 30 min prior to reperfusion, was evaluated in rats with chronic post‑ischemic pain. The pain behavior of the rats was tested with a von Frey filament. Phosphorylation of N‑methyl‑D‑aspartate (NMDA) receptors in the L4/6 section of the spinal cord was measured on the third day following reperfusion by western blotting. The rats treated with 3 or 10 mg/kg FeTMPyP demonstrated significant increases in their paw withdrawal thresholds and decreased levels of phosphorylated NMDA receptor subunit 1 compared with those of the vehicle group (all P<0.001). These findings suggest that nitrosative stress, specifically that associated with peroxynitrite, may be involved in the mechanical allodynia and central sensitization that are associated with CRPS I and may provide a rationale for CRPS I treatment strategies using peroxynitrite decomposition catalysts.

Although remote ischemic preconditioning (RIPC) is an organ-protective maneuver from subsequent ischemia reperfusion injury (IRI) by application of brief ischemia and reperfusion to other organs, its mechanism remains unclear. However, it is known that RIPC reduces the heart, brain, and liver IRI, and that nitric oxide (NO) is involved in the mechanism of this effect. To identify the role of NO in the protective effect of RIPC in renal IRI, this study examined renal function, oxidative status, and histopathological changes using N-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor. Remote ischemic preconditioning was produced by 3 cycles of 5 minutes ischemia and 5 minutes reperfusion. Blood urea nitrogen, creatinine (Cr), and renal tissue malondialdehyde levels were lower, histopathological damage was less severe, and superoxide dismutase level was higher in the RIPC + IRI group than in the IRI group. The renoprotective effect was reversed by L-NAME. Obtained results suggest that RIPC before renal IRI contributes to improvement of renal function, increases antioxidative marker levels, and decreases oxidative stress marker levels and histopathological damage. Moreover, NO is likely to play an important role in this protective effect of RIPC on renal IRI.

Ryu TH, et al. Korean J Pain. 2010 Mar;23(1):1-10. https://doi.org/10.3344/kjp.2010.23.1.1