Carbon Monoxide Rescues the Developmental Lethality of Experimental Rat Models of Rhabdomyolysis-Induced Acute Kidney Injury.

Many victims, after being extricated from a collapsed building as the result of a disaster, suffer from disaster nephrology, a term that is referred to as the crush syndrome (CS). Recommended treatments, which include dialysis or the continuous administration of massive amounts of fluid are not usually easy in cases of such mass natural disasters. In the present study, we examined the therapeutic performance of a biomimetic carbon monoxide (CO) delivery system, CO-enriched red blood cells (CO-RBCs), on experimental animal models of an acute kidney injury (AKI) induced by traumatic and nontraumatic rhabdomyolysis, including CS and rhabdomyolysis with massive hemorrhage shock.

Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury.

Rhabdomyolysis-associated acute kidney injury (AKI) is a serious life-threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood.

Pharmacokinetic Properties of Single and Repeated Injection of Liposomal Platelet Substitute in a Rat Model of Red Blood Cell Transfusion-Induced Dilutional Thrombocytopenia.

A preclinical study of dodecapeptide ((400)HHLGGAKQAGDV(411)) (H12)-(adenosine diphosphate, ADP)-liposomes for use as a synthetic platelet (PLT) substitute under conditions of red blood cell (RBC) transfusion-induced dilutional thrombocytopenia is limited to pharmacological effect. In this study, the pharmacokinetics of H12-(ADP)-liposomes in RBC transfusion-induced dilutional thrombocytopenic rats were evaluated. As evidenced by the use of (14) C, (3) H double-radiolabeled H12-(ADP)-liposomes in which the encapsulated ADP and liposomal membrane were labeled with (14) C and (3) H, respectively, the H12-(ADP)-liposomes remained intact in the blood circulation for up to 3 h after injection, and were mainly distributed to the liver and spleen.

Kupffer cell inactivation by carbon monoxide bound to red blood cells preserves hepatic cytochrome P450 via anti-oxidant and anti-inflammatory effects exerted through the HMGB1/TLR-4 pathway during resuscitation from hemorrhagic shock.

Red blood cell (RBC) transfusions for controlling hemorrhaging induce systemic ischemia reperfusion, resulting in a decrease in hepatic cytochrome P450 (CYP) levels. Carbon monoxide (CO), when bound to red blood cells (CO-RBC) has the potential to protect the hepatic CYP protein to produce a resuscitative effect in a hemorrhagic shock rat model. The aim of this study was to investigate the mechanism by which CO-RBC resuscitation from a massive hemorrhage protects against a decrease in hepatic CYP.

Effect of Repeated Injections of Adenosine Diphosphate-Encapsulated Liposomes Coated with a Fibrinogen γ-Chain Dodecapeptide Developed as a Synthetic Platelet Substitute on Accelerated Blood Clearance in a Healthy and an Anticancer Drug-Induced Thrombocytopenia Rat Model.

Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen γ-chain dodecapeptide [H12 (dodecapeptide ((400) HHLGGAKQAGDV(411) ))-(ADP)-liposome] is a synthetic platelet substitute, in which the surface is covered with polyethylene glycol (PEG). It has been reported that repeated injections of PEGylated liposomes induce an accelerated blood clearance (ABC) phenomenon, which involves a loss in the long-circulation half-life of the material when administered repeatedly to the same animals. The objective of this study was to determine whether the ABC phenomenon was induced by repeated injections of H12-(ADP)-liposome in healthy and anticancer drug-induced thrombocytopenia model rats.

Carbon monoxide-bound red blood cell resuscitation ameliorates hepatic injury induced by massive hemorrhage and red blood cell resuscitation via hepatic cytochrome P450 protection in hemorrhagic shock rats.

Red blood cell (RBC) transfusions are the gold standard in cases of massive hemorrhage, but induce hepatic ischemia-reperfusion injury, a serious complication associated with hemorrhage and RBC resuscitation. Thus, the development of a novel resuscitable fluid that is not associated with hepatic ischemia-reperfusion injury would be desirable. It was reported that exogenous carbon monoxide (CO) treatment ameliorated hepatic ischemia-reperfusion injury accompanying liver transplantation.

Pharmacokinetic study of the structural components of adenosine diphosphate-encapsulated liposomes coated with fibrinogen γ-chain dodecapeptide as a synthetic platelet substitute.

Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, ADP-encapsulated liposomes [H12-(ADP)-liposomes] were developed as a synthetic platelet alternative that specifically accumulates at bleeding sites as the result of interactions with activated platelets via glycoprotein IIb/IIIa and augments platelet aggregation by releasing ADP. The aim of this study is to characterize the pharmacokinetic properties of H12-(ADP)-liposomes and structural components in rats, and to predict the blood retention of H12-(ADP)-liposomes in humans. With use of H12-(ADP)-liposomes in which the encapsulated ADP and liposomal membrane cholesterol were radiolabeled with (14)C and (3)H, respectively, it was found that the time courses for the plasma concentration curves of (14)C and (3)H radioactivity showed that the H12-(ADP)-liposomes remained intact in the blood circulation for up to 24 hours after injection, and were mainly distributed to the liver and spleen.

Carbon monoxide-bound red blood cells protect red blood cell transfusion-induced hepatic cytochrome P450 impairment in hemorrhagic-shock rats.

Red blood cell (RBC) transfusions for massive hemorrhage induce systemic ischemic-reperfusion and influence the disposition and pharmacological activity of drugs as a result of a reduction in the level of expression and activity of cytochrome P450s (P450). It was reported that, when organ-preserving solutions are exposed to carbon monoxide (CO), the treatment was effective in suppressing the postreperfusion reduction in renal P450 levels in cases of kidney transplantation. Therefore, we hypothesized that transfusions with RBC that contain bound CO (CO-RBC) would protect the hepatic level of rat P450 during a massive hemorrhage, compared with plasma expanders and RBC resuscitation.

Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model.

Aims: Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy.

Fluid resuscitation with hemoglobin vesicles prevents Escherichia coli growth via complement activation in a hemorrhagic shock rat model.

Hemoglobin vesicles (HbVs) could serve as a substitute for red blood cells (RBCs) in resuscitation from massive hemorrhage. A massive transfusion of RBCs can increase the risk of infection, which is not caused by contaminating micro-organisms in the transfused RBCs but by a breakdown of the host defense system. We previously found that complement activity was increased after resuscitation with HbVs at a putative dose in a rat model of hemorrhagic shock.