Prevention Of Ischemia-reperfusion Injury Research Articles

Human concentrations of uric acid scavenges adaptive and maladaptive reactive oxygen species in isolated rat hearts subjected to ischemic stress.

Uric acid is a purine degradation product but also an important antioxidant and reactive oxygen species (ROS) scavenger. Experimental settings that mimic myocardial ischemia-reperfusion have not included uric acid despite that it is always present in human extracellular fluid and plasma. We hypothesized that uric acid has an important role in myocardial ROS scavenging. Here, we tested the cardiac response to uric acid on infarct size following ischemia-reperfusion with and without exacerbated oxidative stress due to acute pressure overload and during preconditioning. We also examined mitochondrial respiration and ROS-induced mitochondrial permeability transition pore opening. Under exacerbated ROS stress induced by high-pressure perfusion, uric acid lowered oxidative stress and reduced infarct size. In contrast, uric acid blocked cardioprotection induced by ischemic preconditioning. However, this effect was reversed by probenecid, an inhibitor of cellular uptake of uric acid. In accordance, in intact cardiomyocytes, extracellular uric acid reduced the susceptibility of mitochondria towards opening of the permeability transition pore, suggesting that uric acid may prevent ischemia-reperfusion injury due to scavenging of maladaptive ROS. Moreover, as uric acid also scavenges adaptive ROS, this may interfere with preconditioning. Altogether, uric acid might be a confounder when translating preclinical experimental results into clinical treatment.

Supplementing preservation solution with mitochondria-targeted H2 S donor AP39 protects cardiac grafts from prolonged cold ischemia-reperfusion injury in heart transplantation.

Heart transplant has been accepted as the standard treatment for end-stage heart failure. Because of its susceptibility to ischemia-reperfusion injury, the heart can be preserved for only 4 to 6hours in cold static preservation solutions. Prolonged ischemia time is adversely associated with primary graft function and long-term survival. New strategies to preserve donor hearts are urgently needed. We demonstrate that AP39, a mitochondria-targeting hydrogen sulfide donor, significantly increases cardiomyocyte viability and reduces cell apoptosis/death after cold hypoxia/reoxygenation in vitro. It also decreases gene expression of proinflammatory cytokines and preserves mitochondria function. Using an in vivo murine heart transplant model, we show that preserving donor hearts with AP39-supplemented University of Wisconsin solution (n=7) significantly protects heart graft function, measured by quantitative ultrasound scan, against prolonged cold ischemia-reperfusion injury (24hours at 4°C), along with reducing tissue injury and fibrosis. Our study demonstrates that supplementing preservation solution with AP39 protects cardiac grafts from prolonged ischemia, highlighting its therapeutic potential in preventing ischemia-reperfusion injury in heart transplant.

Abstract 875: Cardiomyocyte Derived DDT Protects Against Myocardial Infarction Induced Heart Failure

Background: D-dopachrome tautomerase (DDT), the only homolog of macrophage migration inhibitory factor (MIF), is a cytokine highly expressed in cardiomyocytes and has autocrine-paracrine effects, signaling through the CD74 receptor. Endogenous DDT and MIF prevent ischemia-reperfusion injury in mice. In this study, we investigated whether endogenous cardiomyocyte DDT protects against myocardial remodeling and heart failure after myocardial infarction. Methods: Cardiomyocyte-specific DDT knockout (cKO) and littermate control (CON) mice underwent myocardial infarction (MI) or sham surgery. Serial echocardiography was performed at baseline, 1 day before permanent coronary ligation and 1 day, 1 week, and 4 weeks after MI or sham surgery. Hearts were analyzed at 3 days after MI or sham surgery for histology and molecular studies. Results: No baseline differences in left ventricular (LV) function were observed in cKO and CON mice at baseline or after sham surgery. The initial infarction sizes were comparable at 1 day after coronary ligation in cKO and CON. Compared to CON, cKO mice developed more rapid LV dilatation, and decreased LV ejection fraction (EF) and stroke volume (SV) as early as 1 week after MI. At 4 weeks after MI, LVEF was 33% lower and SV lower by 43% in cKO vs. CON (n=4-5/group, all P<0.01). Hemodynamic analysis showed that LV end diastolic pressure in the cKO mice was 38% higher in cKO vs. CON after 4 weeks MI (p=0.052). Immunoblots showed diminished phosphorylation of AMPK and downstream ACC in the cKO mice 3 days after MI. Immunohistochemistry staining with CD3 and F4/80 staining showed increased T cells and macrophage cells in the cKO mice 3 days after MI (p<0.05). We further assessed the regulation of cardiac DDT expression in chronic human heart failure. In hearts explanted from patients with advanced heart failure during transplantation for ischemic cardiomyopathy (n=8), DDT mRNA and protein expression were also reduced by 40% and 58% compared to controls (P<0.01). Conclusion: Cardiomyocyte-derived DDT prevents adverse cardiac remodeling after MI, potentially through AMPK signaling and anti-inflammatory effects. Down-regulation of cardiac DDT may contribute to pathogenesis of advanced heart failure.

Research advancement on the electric stimulation in the ischemia and reperfusion injury

Ischemia and reperfusion injury has a serious effect on the organs’function. How to protect organs from injury and reduce organ damage during ischemia-reperfusion period is the main concerns of many researches. It is reported that electrical stimulation can alleviate ischemia and reperfusion injury of some organs. In this paper, we will review the effect of electric stimulation on organ ischemia-reperfusion injury and analyze the mechanism of electric stimulation and provide new ideas for the prevention and treatment of clinical organ ischemia-reperfusion injury. Key words: Electric stimulation; Reperfusion injury; Organ protection

Remote ischemic conditioning in septic shock (RECO-Sepsis): study protocol for a randomized controlled trial

BackgroundSeptic shock is a major public health problem that is associated with up to 50% mortality. Unfavorable outcomes are mainly attributed to multiple organ failure (MOF) resulting from an uncontrolled inflammatory response and ischemia-reperfusion processes. REmote ischemic COnditioning (RECO) is a promising intervention to prevent ischemia-reperfusion injury. We hypothesize that RECO would reduce the severity of septic shock-induced MOF.Methods/designRECO in septic shock patients (RECO-Sepsis study) is an ongoing, prospective, multicenter, randomized, open-label trial, testing whether RECO, as an adjuvant therapy to conventional treatment in septic shock, decreases the severity of MOF as assessed by the Sequential Organ Failure Assessment (SOFA) score. Adult patients admitted to an intensive care unit with documented or suspected infection, lactatemia > 2 mmol/l, and treated with norepinephrine for less than 12 h are potentially eligible for the study. Non-inclusion criteria are: having expressed the wish not to be resuscitated, contraindication for the use of a brachial cuff on both arms, intercurrent disease with an expected life expectancy of less than 24 h, cardiac arrest, and pregnant or breastfeeding women. After enrollment, patients are randomized (n = 180) 1:1 to receive RECO or no adjunctive intervention. RECO consists of four cycles of cuff inflation to 200 mmHg for 5 min and then deflation to 0 mmHg for another 5 min. RECO is performed at inclusion and repeated 12 and 24 h later. The primary endpoint is the mean daily SOFA score up to day 4 after inclusion. Secondary outcomes include the need for organ support, hospital length of stay, and 90-day mortality.DiscussionResults of this proof-of-concept trial should provide information on the efficacy of RECO in patients with septic shock.Trial registrationClinicalTrials.gov, ID: identifier: NCT03201575. Registered on 28 June 2017.

Research progress on prevention and treatment of ischemia-reperfusion injury in intestinal transplantation

Intestinal transplantation is the only treatment option for irreversible intestinal failure and parenteral nutrition failure. Although the progress of immunosuppressive therapy and the improvement of surgical techniques have improved the prognosis of intestinal transplantation, it is still unsatisfactory compared with other solid organ transplantation, mainly due to the fact that the intestinal mucosa is susceptible to damage due to ischemia. The basic pathophysiological process of ischemia-reperfusion injury(IRI) is that ischemia/reperfusion induces the production of reactive oxygen species (ROS), inflammation and cell apoptosis, leading to tissue damage. In recent years, the pathophysiology of ischemia-reperfusion injury in intestinal transplantation has made some new progress, providing more possibilities for the prevention and treatment of intestinal transplantation IRI.Although most of them are animal experimental results, they have important reference value for clinical application. Key words: Intestine, small; Organ transplantation; Reperfusion injury; Ischemic preconditioning; Review

Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus.

The role of hormones in renal disease and ischemia-reperfusion injury.

The patients with renal diseases, especially end-stage renal disease (ESRD), are at high risk of developing cardiovascular disturbances. Some hormones such as brain natriuretic peptide appear to be important serum biomarkers in predicting cardiac death in ESRD patients. Renal diseases cause inflammation, anemia, uremic toxins, fluid overload, and electrolyte disturbance. Kidney transplantation is considered the choice treatment for patients with ESRD. Ischemia-reperfusion (IR), which occurs during renal transplantation is one of the factors that affect the outcome of renal transplantation. Renal graft rejection is the result of IR injury and there is no effective treatment to prevent IR injury. Reperfusion after ischemia may cause injury through generation of reactive oxygen and nitrogen species, inflammatory responses by increased levels of tumor necrosis factor-α (TNF-α) and interleukins (IL), and apoptotic processes, and leads to acute kidney injury (AKI). Thus, antioxidant, anti-apoptotic and anti-inflammatory hormones, which inhibit these pathways, can protect against IR injury and improve transplanted renal function in patients with ESRD.

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles.

Protein kinase C-delta inhibitor (PKCδi) is a promising drug to prevent ischemia-reperfusion-induced organ injury. It is usually conjugated to a cell-penetrating peptide, TAT, for intracellular delivery. However, TAT has shown non-specific biological activities. Gold nanoparticles (GNPs) can be used as drug delivery carriers without recognized toxicity. Therefore, we have used a GNP/peptide hybrid to deliver PKCδi. Two short peptides (P2: CAAAAE and P4: CAAAAW), at a 95:5 ratio, were used to modify the surface properties of GNP. GNPs conjugated with PKCδi (GNP/PKCi) are stable in distilled water, 0.9% NaCl, and phosphate-buffered saline (PBS) containing bovine serum albumin or fetal bovine serum. Intravenous injection of GNP-PKCi was previously shown to prevent ischemia-reperfusion injury of the lung. This article outlines a protocol to formulate GNP/PKCi and assess the physiochemical properties of GNP/PKCi. We have used similar methods to formulate other peptide-based drugs with GNP. This article will hopefully draw more attention to this novel intracellular drug delivery technology and its applications in vivo.

Early Protection by Resveratrol in Rat Lung Transplantation.

BackgroundResveratrol is a multifunctional bioactive substance that has effects in anti-inflammation and prevention of ischemia-reperfusion injury. This study compared the inflammation and expression of related proteins during the early stages after transplantation to explore the effects and mechanisms of resveratrol on transplanted lung.Material/MethodsSprague-Dawley rats were randomized to receive pretreatment of resveratrol suspension (60 mg/kg; RES group), dexamethasone (1 mg/kg; DEM group), or normal saline solution (2 mL/kg; control group) 1 h before lung transplantation. The cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) of the recipients was determined 24 h after transplantation. Histopathologic evaluation, including lung injury score, and the expression of necroptosis-associated proteins was assessed.ResultsHistopathologic evaluation showed pneumocyte damage and endothelialitis associated with hemorrhage in the alveoli in the control group, the severity of which was greater than that in the other 2 groups. The levels of interleukin-6 and tumor necrosis factor-α in the serum and BALF of the RES and DEM groups were lower than those in the control group. The expression of necroptosis-associated proteins in the RES group was lower than that in the control group, and was inversely proportional to lung injury.ConclusionsPretreatment with resveratrol protected rat lung in the early stages after transplantation. We determined a relationship between necroptosis-associated proteins and transplanted lung injury, which suggests that the mechanism of lung transplantation-associated ischemia-reperfusion injury may be related to necroptosis.

Comparison of effects of melatonin, pentoxifylline and dimethyl sulfoxide in experimental liver ischemia-reperfusion injury by three different methods

Objectives: Liver transplantation is increasingly being used in the treatment of end-stage liver disease. Ischemia-reperfusion injury is one of the major problems encountered in transplantation. In this study, we aimed to compare the effects of melatonin, pentoxifylline, and dimethyl sulfoxide (DMSO), in hepatic ischemia-reperfusion injury with different methods such as biochemical/ultrastructural changes and hepatobiliary scintigraphy. Methods: Thirty rabbits were used in the Laboratory of Experimental Animals of Trakya University under appropriate conditions. Sham laparotomy and only ischemia reperfusion group were planned. They were used melatonin, pentoxifylline, and DMSO after ischemia-reperfusion in the other three groups. 6 rabbits were randomly selected for each group. Rabbits in all groups were subjected to liver scintigraphy. Following scintigraphy, 2 cm2 of liver tissue was removed to examining for liver antioxidant enzyme levels (superoxide dismutase [SOD] and glutathione peroxidase [GPx]) and for liver electron microscopy. Results: Pentoxifylline and melatonin protected significantly uptake and excretion functions in liver scintigraphy. When the effects of all three substances were examined by electron microscopy, it was found that the three substances protected the liver from the effects of ischemia-reperfusion damage at varying rates. All three agents were found to protect SOD and GPx from falling in various amounts. Conclusions: Studies to prevent ischemia-reperfusion injury, which may develop as a result of the Pringle maneuver applied to liver transplantations as well as to liver resections or liver injuries, still maintain their popularity. In our study, the effects of agents were identified in three different ways. Ischemia-reperfusion injury-reducing effect of pentoxifylline gave parallel results with three methods.

The Zingiber officinale Roscoe Reduces Chest Pain on Patients Undergoing Coronary Angioplasty: A Clinical Trial

Introduction: Evidence from animal studies suggests that Zingiber officinale (ginger) may help prevent ischemia–reperfusion injury (IRI) in heart. The aim of the present study was to investigate the effect of ginger on inducing preconditioning on patients undergoing angioplasty. Methods: Thirty-four patients, referred for elective angioplasty, were randomly divided into the control (17 patients) and ginger groups (17 patients). Subjects in the experimental group were provided 250 mg ginger powder in Zintoma capsules per day for 10 days, whereas those in the control group received placebo. The patients underwent percutaneous transluminal coronary angioplasty (PTCA) (One 45-second balloon inflation and 2 minutes reperfusion). Chest pain scores were assessed immediately after angioplasty and cardiac injury biomarkers were assessed 12 hours later. Results: The average pain score during the balloon inflation in the ginger group was significantly lower than the control group (2.1±1 versus 3.8±1.5, P = 0.04). Troponin I was elevated in both groups after angioplasty, but there was not any significant difference between groups in this regard (P = 0.12 and 0.10, respectively). Conclusion: The use of ginger reduces chest pain during coronary angioplasty but its effect on the release of biochemical markers of myocardial damage is obscure.

Study of Different Therapeutic Agents for the Prevention of Ischemia Reperfusion Injury in Free Skin Flap

Background: In clinical practice a certain fraction of skinflap transfers fail invariably because of ischemia-reperfusioninjury. This study was designed to develop experimental modelof ischemia-reperfusion injury in rat skin flap to investigatethe effect of certain pharmacological agents on prevention orreducing ischemia-reperfusion injury.Methods: A “4x6” cm hemi epigastric skin flap of adultalbino rat was raised and subjected to 8 hours of ischemiathen reperfusion for 48 hours. A total of 40 flaps were studiedand divided randomly into 5 groups. 15 minutes prior toreperfusion, all flaps (except group I) were infused by saline,Vitamin C, Heparin, and Monoclonal antibody LY-6G togroups II, III, IV and V respectively. After 2 days, macroscopicevaluation of flap survival, histological study of neutrophilinfiltration, and biochemical tissue enzymes assay wereperformed.Results: All flaps survived completely in sham group Iwith minimal neutrophilia while the mean percentage of flapnecrosis in control group II was 90.5% with massive neutrophilia.The mean percentage of flap survival were 71, 80,and 84 percent in groups III, IV, and V respectively. Neutrophilcount of flap tissue showed significant reduction as comparedwith control flaps. Tissue enzymes assay showed stable levelof superoxide dismutase activity in flaps pretreated by drugscompared to control group. Caspase-3 enzyme activity showedvariable decrements in flaps pretreated with the differentdrugs when compared with control flaps.Conclusion: The use of certain pharmacological agentscould significantly reduce the effect of ischemia-reperfusioninjury on skin flaps.

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice.

Background and objective: Renal ischaemia reperfusion injury (IRI), characterized by excessive cell apoptosis and inflammation, remains a clinical challenge. Mitochondrial membrane potential is related to apoptosis and inflammation of IRI. Previous studies have indicated that uncoupling protein 2 (UCP2) and its receptors play an important role in inflammation, apoptosis and injuries, especially in oxidative stress injury. However, the underlying mechanisms of UCP2 in IRI are still not fully understood.Methods and results: In the present study, male C57 mice were randomly divided into three groups:sham, IR, and UCP2-/-+IR. The IRI model was established by removing the right kidney and clamping the left kidney for 45 min followed by reperfusion. Blood urea nitrogen (BUN) and creatinine were higher in UCP2-/-+IR mouse serum than in IR mouse serum. In addition, relative to the IR group, UCP2-/-+IR mouse renal cells had increased reactive oxygen species (ROS) production, aggravating tissue damage. We examined changes in the NFκB pathway and found that after UCP2 knockdown, IκB and IKK phosphorylation increased, and nuclear NFκB increased, which stimulated inflammation. Moreover, there was an increase in apoptosis in the UCP2-/-+IR group.Conclusion: UCP2 can prevent IRI in C57 mice. Mechanistically, UCP2 may decrease ROS expression, NFκB activation and caspase-3 cleavage, rendering UCP2 a potential therapeutic target against IRI.

Targeting HIF-1α to Prevent Renal Ischemia-Reperfusion Injury: Does It Work?

Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.

EPURE Transplant (Eplerenone in Patients Undergoing Renal Transplant) study: study protocol for a randomized controlled trial

BackgroundDespite advances in immunosuppressive therapy, kidney graft survival has failed to improve during the last decades. Ischemia/reperfusion injury (IRI) is one of the main pathophysiological mechanisms underlying delayed graft function, which is associated with poor long-term graft survival. Due to organ shortage, the proportion of grafts from expanded criteria donors (ECDs) is ever growing. These grafts may particularly benefit from IRI prevention. In preclinical models, mineralocorticoid receptor antagonists (MRAs) have been shown to efficiently prevent IRI. This study aims to assess the effect of MRA administration in the early phase of kidney transplantation (KT) among recipients of ECD grafts on mid-term graft function.Methods/designThis is a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients on hemodialysis and undergoing a single or a dual KT from an ECD will be eligible for inclusion. We plan to randomize 132 patients. Included patients will be randomized (1:1) to receive either eplerenone 25 mg every 12 h during 4 days (the first dose being administered just prior to KT) or placebo. The primary outcome is graft function at 3 months, assessed by glomerular filtration rate (GFR, in mL/min/1.73m2) measured using iohexol clearance. Secondary outcomes include (1) proportion of patients with either dialysis dependency or a GFR < 30 mL/min/1.73m2 at 3 months, (2) proportion of patients with immediate, slow, or delayed graft function, (3) proteinuria at 3 months, (4) occurrence of hyperkalemia during the first week following KT, (5) length of hospital stay for the KT, and (6) occurrence of biopsy-proven acute rejection in the first 3 months following KT. Estimated GFR, graft, and patient survival will also be collected at 1, 3, and 10 years via the national database of organ recipients.DiscussionImprovement of ECD grafts is a public health priority, since better ECD outcomes could eventually limit organ shortage. MRA administration in the early phase of KT may prevent IRI and subsequently improve mid-term graft function. The trial will also assess the safety of MRA administration in this population, primarily the absence of threatening hyperkalemia.Trial registrationClinicalTrials.gov, NCT02490904. Registered on 1 July 2015.

Prevention of Ischemia-Reperfusion Injury and Chronic Rejection in a Porcine Vascularized Composite Allotransplantation Model

Prevention of Ischemia-Reperfusion Injury and Chronic Rejection in a Porcine Vascularized Composite Allotransplantation Model

Astaxanthin Prevents Ischemia-Reperfusion Injury of the Steatotic Liver in Mice.

Astaxanthin Prevents Ischemia-Reperfusion Injury of the Steatotic Liver in Mice.

Electroacupuncture Inhibits Apoptosis of Peri-Ischemic Regions via Modulating p38, Extracellular Signal-Regulated Kinase (ERK1/2), and c-Jun N Terminal Kinases (JNK) in Cerebral Ischemia-Reperfusion-Injured Rats.

BackgroundPrevious studies suggested that inhibition of apoptosis prevents the dysfunction of ischemia-reperfusion injury. In the pathogenesis of ischemia-reperfusion injury, JNK/ERK1/2 and p38 play an essential role in regulation of cell apoptosis. Electroacupuncture (EA), a form of acupuncture, has demonstrated superiority in preventing ischemia-reperfusion injury, but the underlying mechanism is unclear. In the present study, we explored the effects of electroacupuncture at Shenting (GV24) and Baihui (GV20) acupoints on focal cerebral ischemia-reperfusion (MCAO) rats, and explored whether JNK/ERK1/2- and p38-mediated cell apoptosis are involved.Material/MethodsThe rats were divided into a sham operation control group, an ischemia group, and an electroacupuncture group with acupuncture applied for 10 days (30 min per day). TTC staining was used to calculate the ischemic brain volume. TUNEL staining and transmission electron microscopy were used to detect cell apoptosis. Western blot analysis and Bio-Plex were used to detect JNK, p38, ERK1/2, Bcl-2, and Bax protein expression.ResultsWe found that electroacupuncture at day 10 significantly reduced cerebral infarction. In addition, electroacupuncture suppressed activation of JNK and p38, while enhancing the activation of ERK1/2 in the peri-ischemic regions. Consequently, the effect of electroacupuncture on these pathways resulted in the inhibition of apoptosis, which was demonstrated by TUNEL and transmission electron microscopy. We found that electroacupuncture upregulated the anti-apoptotic Bcl-2/Bax ratio in peri-ischemic regions.ConclusionsOur findings suggest that inhibition of cell apoptosis via regulating multiple signaling pathways might be a mechanism whereby electroacupuncture has a positive therapeutic effect on post-stroke impairment.

Late night salivary cortisol, stress-resilience and Type 2 diabetes mellitus. Findings from population-based KORA Age study

The main limitation to successful transplantation is the antigraft response developed by the recipient immune system, and the adverse side effects of immunosuppressive agents which are associated with significant toxicity and counter indications such as infection and cancer. Furthermore, immunosuppressants do little to prevent ischemia-reperfusion injury during the transplantation procedure itself hence there is a growing need to develop novel immunosuppressive drugs specifically aimed at prolonging graft survival. Linear tetrapyrroles derived from the breakdown of mammalian heme have been shown in numerous studies to play a protective role in allograft transplantation and ischemia-reperfusion injury; however, commercial sources of these products have not been approved for use in humans. Plants and algae produce equivalent linear tetrapyrroles called bilins that serve as chromophores in light-sensing. One such marine-derived tetrapyrrole, phycocyanobilin (PCB), shows significant structural similarity to mammalian biliverdin (BV) and may prove to be a safer alternative for use in the clinic if it can exert direct effects on human immune cells. Using a mixed lymphocyte reaction, we quantified the allogeneic responses of recipient cells to donor cells and found that PCB, like BV, effectively suppressed proliferation and proinflammatory cytokine production. In addition, we found that BV and PCB can directly downregulate the proinflammatory responses of both innate dendritic cells and adaptive T cells. We therefore propose that PCB may be an effective therapeutic drug in the clinical setting of transplantation and may also have wider applications in regulating inappropriate inflammation.