Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

Abstract

Background: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO 2 ) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO 2 nanoparticles on hepatic ischemia reperfusion injury. Methods: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO 2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO 2 nanoparticle group (IR+ CeO 2 ). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Results: Prophylactic treatment with CeO 2 nanoparticles (0.5mg/kg i.v (IR+CeO 2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Conclusion: Taken together, these data suggest that CeO 2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.Room 315,

Effects of cerium oxide nanoparticles on hemostasis: Coagulation, platelets, and vascular endothelial cells

“…Our results showed that NC modulate the inflammatory response, decreasing VCAM‐1 surface exposure, involved in the leukocyte recruitment, and the release of cytokines, IL‐6 and IL‐8. These findings are consistent with those of previous studies that have shown a protective effect of NC on oxidative and inflammatory response …”

“…These findings are consistent with those of previous studies that have shown a protective effect of NC on oxidative and inflammatory response. [57][58][59][60][61] Previous studies demonstrated that a disturbance of the oxidative balance may lead to premature senescence associated with telomere shortening. 62,63 There is little information on the effects of nanomaterials on oxidative stress-induced senescence in human cells.…”

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

“…These studies mainly address the impact of hypothermic vs. cold storage machine perfusion, whereas alternative approaches for organ conditioning are tested solely in pre-clinical models (35–37) or have been proven insufficient (38). In this context, targeting IRI by applying various treatment schemes has been illustrated in an extensive number of experimental trials (37, 39, 40). For instance, ATLG was seen to be effective in preventing IRI-associated renal function impairment, tissue damage and tubular apoptosis when applying ATLG to the recipient (41).…”

Unintended effects of drug carriers: Big issues of small particles

“…There are instances where biodegradable nanoparticles are non-biocompatible and where non-biodegradable nanoparticles are biocompatible. These can occur when the nanoparticle degradation byproducts induce inflammatory or toxic effects [1,15,27], or when a non-biodegradable nanoparticles induces anti-oxidant or cytoprotective effects [28–30]. …”