Mechanism of Dimethyl Sulfoxide-Induced Hemolysis

Norred, William P.; Ansel, Howard C.; Roth, Ivan L.; Peifer, James J.

doi:10.1002/jps.2600590509

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Further, DMSO also caused a significant decrease in the RBC count (P < 0.05) as compared to the control group (Table 2). The decrease in RBC count could be explained by the ability of DMSO to cause intravascular hemolysis, as previously described[29, 30]. However, DMSO did not cause any detectable hepatic or renal toxicity at the concentration used (Table 3).…”

Section: Resultssupporting

confidence: 63%

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PF-04886847 (an Inhibitor of Plasma Kallikrein) Attenuates Inflammatory Mediators and Activation of Blood Coagulation in Rat Model of Lipopolysaccharide (LPS) - Induced Sepsis

Kolte

Bryant²,

Gibson³

et al. 2012

CHAMC

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The plasma kallikrein-mediated proteolysis regulates both thrombosis and inflammation. Previous study has shown that PF-04886847 is a potent and competitive inhibitor of kallikrein, suggesting that it might be useful for the treatment of kallikrein-kinin mediated inflammatory and thrombotic disorders. In the rat model of lipopolysaccharide (LPS) -induced sepsis used in this study, pretreatment of rats with PF-04886847 (1 mg/kg) prior to LPS (10 mg/kg) prevented endotoxin-induced increase in granulocyte count in the systemic circulation. PF-04886847 significantly reduced the elevated plasma 6-keto PGF1α levels in LPS treated rats, suggesting that PF-04886847 could be useful in preventing hypotensive shock during sepsis. PF-04886847 did not inhibit LPS-induced increase in plasma TNF-α level. Pretreatment of rats with PF-04886847 prior to LPS did not attenuate endotoxin-induced decrease in platelet count and plasma fibrinogen levels as well as increase in plasma D-dimer levels. PF-04886847 did not protect the animals against LPS-mediated acute hepatic and renal injury and disseminated intravascular coagulation (DIC). Since prekallikrein (the zymogen form of plasma kallikrein) deficient patients have prolonged aPPT without having any bleeding disorder, the anti-thrombotic property and mechanism of action of PF-04886847 was assessed. In a rabbit balloon injury model designed to mimic clinical conditions of acute thrombotic events, PF-04886847 reduced thrombus mass dose-dependently. PF-04886847 (1 mg/kg) prolonged both activated partial thromboplastin time (aPTT) and prothrombin time (PT) in a dose-dependent manner. Although the findings of this study indicate that PF-04886847 possesses limited anti-thrombotic and anti-inflammatory effects, PF-04886847 may have therapeutic potential in other kallikrein-kinin mediated diseases.

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Section: Resultssupporting

confidence: 63%

“…The optimal concentration of DMSO to reconstitute PF-04886847 was empirically determined. The toxicity of DMSO is well established in the literature for decades[29, 30]. Thus, very few rats were used for the DMSO studies so that pointless test and suffering could be reduced.…”

Section: Methodsmentioning

confidence: 99%

PF-04886847 (an Inhibitor of Plasma Kallikrein) Attenuates Inflammatory Mediators and Activation of Blood Coagulation in Rat Model of Lipopolysaccharide (LPS) - Induced Sepsis

Kolte

Bryant²,

Gibson³

et al. 2012

CHAMC

View full text Add to dashboard Cite

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“…The blood was obtained from healthy male adult humans and immediately collected and defibrinated as described by Norred et al [40] before use in the hemolysis assay. The blood was defibrinated by swirling gently with five to seven glass beads for about 5 minutes, then the defibrinated blood was decanted in a clean container without touching the beads to be employed in the hemolysis assay.…”

Section: Blood Samples Used In Hemolysis Assaymentioning

confidence: 99%

Chemical Investigation and Cytotoxic Activity of Bee Venoms Collected by Dissection and Electric-Shocked Methods.

Badria¹,

Fathy²,

Fetehe³

et al. 2018

J Apither

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Introduction:Cancer is a large group of disorders characterized by uncontrolled cellular proliferation. It is one of the most devastating diseases all over the world. Recently, there is an increased interest in the clinical use of natural products as a safe, efficient, and economic therapeutic alternative. Honeybee products therapy, apitherapy, was used to control various diseases including cancer. Objectives: The primary objective of this study was to screen the potential cytotoxic effects of bee venoms (BVs) against different cancer types and also to evaluate the reported bee venoms-caused hemolysis on human red blood cells. Materials and Methods: Samples of venom were collected from different Egyptian localities with different techniques and tested by 3-(4,5-dimethyl-thiazolyl)-2,5-diphenyltetrazolium bromide cell-based assay against liver (Hep-G2), colorectal (Caco-2), and breast (MCF-7) cancer cell lines. Also, different concentrations of BVs were used to evaluate the hemolysis percentage caused by BVs if injected into the circulation. Results:The results showed that Italian dissected method-BV was the most active among all the tested samples against Hep-G2 (93.92%), Caco-2 (93.92%), and MCF-7 (90.17%). In addition, all BVs at all concentrations caused high hemolysis percentage. Conclusion:The results showed that BV is an interesting agent that has valuable activities against Hep-G2, Caco-2, and MCF-7. Being the most effective agent against cancer cell lines, BV might be incorporated in cancer remedy regimens after further studies but the inherent limitation that BVs cause severe hemolysis to blood cells at low concentrations would require more research to avoid the risk of using BV in vivo.

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“…Studies from the 1960s [30] showed that when administered intravenously, DMSO is a potent hemolytic agent. A more recent study has reported on the toxic effects of DMSO on endothelial and red blood cells and platelets [31,32], all three key players in the chain of cellular events in SCD that ultimately lead to vaso-occlusion and multiple organ damage Given its effects on RBCs [24][25][26][27], [29][30][31][32], DMSO could be viewed as a "sickle cell disease-mimetic" (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Dimethyl Sulfoxide Induces Hemolysis and Pulmonary Hypertension

Tofovic

Bilan

Rafikova

et al. 2022

Prilozi

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Vascular and lung injury are well established complications associated with hemolytic disorders, and hemolysis associated pulmonary hypertension (PH) has emerged as the most serious complication of sickle cell disease. The causal relationship between intravascular hemolysis and the development of PH is still under investigation. Previously we have shown that repetitive administration of hemolyzed autologous blood causes PH in rats. Dimethyl sulfoxide (DMSO), a widely used solvent and anti-inflammatory agent, induces hemolysis in vivo. We hypothesized that repetitive administration of DMSO would induce PH in rats. We also examined hemolysis-induced release of adenosine deaminase (ADA) and arginase from red blood cells, which may amplify hemolysis-mediated vascular injury. Acute administration of DMSO (1.5ml/30 min into the right atrium) induced intravascular hemolysis and pulmonary vasoconstriction. DMSO-induced increase in right ventricular peak systolic pressure (RVPSP) was associated with increased release of ADA. Notably, the acute increase in RVPSP was attenuated by administration of an adenosine A2A receptor agonist or by pretreatment of animals with ADA inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). Repetitive administration of DMSO for 10 days produced anemia, hemoglobinuria, hemoglobinemia, splenomegaly, and development of PH. Histopathological analysis revealed pulmonary vascular remodeling. The presented data describe a new model of hemolysis induced PH, suggesting that hemolysis is mechanistically related to pulmonary hypertension, and pointing to a potential pathogenic role that adenosine deaminase and accelerated adenosine metabolism may play in hemolysis associated pulmonary hypertension.

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Mechanism of Dimethyl Sulfoxide-Induced Hemolysis

Cited by 7 publications

References 34 publications

PF-04886847 (an Inhibitor of Plasma Kallikrein) Attenuates Inflammatory Mediators and Activation of Blood Coagulation in Rat Model of Lipopolysaccharide (LPS) - Induced Sepsis

PF-04886847 (an Inhibitor of Plasma Kallikrein) Attenuates Inflammatory Mediators and Activation of Blood Coagulation in Rat Model of Lipopolysaccharide (LPS) - Induced Sepsis

Chemical Investigation and Cytotoxic Activity of Bee Venoms Collected by Dissection and Electric-Shocked Methods.

Dimethyl Sulfoxide Induces Hemolysis and Pulmonary Hypertension

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