Physcion Induces Hemolysis and Premature Phosphatidylserine Externalization in Human Erythrocytes

Akiel, Maaged; Alsughayyir, Jawaher; Basudan, Ahmed; Alamri, Hassan S.; Dera, Ayed A.; Barhoumi, Tlili; Subayyil, A. M. Al; Basmaeil, Yasser; Aldakheel, Fahad M.; Alakeel, Raid; Ghneim, Hazem K.; Al‐Sheikh, Yazeed A.; Alraey, Yasser; Asiri, Saeed Ahmed; Alfhili, Mohammad A.

doi:10.1248/bpb.b20-00744

Cited by 14 publications

(7 citation statements)

References 32 publications

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“…Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were measured using colorimetric kits (Solarbio Life Science) as previously described [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

Alfhili

Aljuraiban

2021

Cells

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Cardiovascular diseases (CVD) are a leading cause of mortality worldwide, and dietary habits represent a major risk factor for dyslipidemia; a hallmark of CVD. Saturated fatty acids contribute to CVD by aggravating dyslipidemia, and, in particular, lauric acid (LA) raises circulating cholesterol levels. The role of red blood cells (RBCs) in CVD is increasingly being appreciated, and eryptosis has recently been identified as a novel mechanism in CVD. However, the effect of LA on RBC physiology has not been thoroughly investigated. RBCs were isolated from heparin-anticoagulated whole blood (WB) and exposed to 50–250 μM of LA for 24 h at 37 °C. Hemoglobin was photometrically examined as an indicator of hemolysis, whereas eryptosis was assessed by Annexin V-FITC for phosphatidylserine (PS) exposure, Fluo4/AM for Ca2+, light scatter for cellular morphology, H2DCFDA for oxidative stress, and BODIPY 581/591 C11 for lipid peroxidation. WB was also examined for RBC, leukocyte, and platelet viability and indices. LA caused dose-responsive hemolysis, and Ca2+-dependent PS exposure, elevated erythrocyte sedimentation rate (ESR), cytosolic Ca2+ overload, cell shrinkage and granularity, oxidative stress, accumulation of lipid peroxides, and stimulation of casein kinase 1α (CK1α). In WB, LA disrupted leukocyte distribution with elevated neutrophil-lymphocyte ratio (NLR) due to selective toxicity to lymphocytes. In conclusion, this report provides the first evidence of the pro-eryptotic potential of LA and associated mechanisms, which informs dietary interventions aimed at CVD prevention and management.

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“…Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were measured using colorimetric kits (Solarbio Life Science) as previously described [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

Alfhili

Aljuraiban

2021

Cells

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“…The process of eryptosis regulation is complex, implicating a multitude of cellular machinery, and there are various triggers and inhibitors. Several kinases, including cyclin-dependent kinase 4, p38 mitogen-activated kinase, casein kinase 1α (CK1α), mitogen- and stress-activated kinase MSK1/2, and Janus-activated kinase JAK3, have been shown to participate in the stimulation or inhibition of eryptosis [ 10 , 19 ]. Many food-derived phytochemicals and natural compounds, including phenolic compounds and alkaloids, with antioxidant and anti-inflammatory properties have been reported to prevent eryptosis-driven cell death and associated clinical conditions [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms and Pathophysiological Significance of Eryptosis

Alghareeb

Alfhili

Fatima

2023

IJMS

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Despite lacking the central apoptotic machinery, senescent or damaged RBCs can undergo an unusual apoptosis-like cell death, termed eryptosis. This premature death can be caused by, or a symptom of, a wide range of diseases. However, various adverse conditions, xenobiotics, and endogenous mediators have also been recognized as triggers and inhibitors of eryptosis. Eukaryotic RBCs are unique among their cell membrane distribution of phospholipids. The change in the RBC membrane composition of the outer leaflet occurs in a variety of diseases, including sickle cell disease, renal diseases, leukemia, Parkinson’s disease, and diabetes. Eryptotic erythrocytes exhibit various morphological alterations such as shrinkage, swelling, and increased granulation. Biochemical changes include cytosolic Ca2+ increase, oxidative stress, stimulation of caspases, metabolic exhaustion, and ceramide accumulation. Eryptosis is an effective mechanism for the elimination of dysfunctional erythrocytes due to senescence, infection, or injury to prevent hemolysis. Nevertheless, excessive eryptosis is associated with multiple pathologies, most notably anemia, abnormal microcirculation, and prothrombotic risk; all of which contribute to the pathogenesis of several diseases. In this review, we provide an overview of the molecular mechanisms, physiological and pathophysiological relevance of eryptosis, as well as the potential role of natural and synthetic compounds in modulating RBC survival and death.

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“…McGill reviewed the mechanisms and interpretation of the plasma levels of ALT and AST elevation in liver injury and stated that ALT and AST have poor prognostic utility in acute liver injury and liver failure ( McGill, 2016 ). In addition, physcion was reported to be cytotoxic to red blood cells by triggering hemolysis and programmed cell death ( Akiel et al, 2021 ). As a result, unpredictable response to the different degree of hemolysis might also affect the accurate measures of such biochemical testing ( Lippi et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of the Major Anthraquinones Derived From Polygoni Multiflori Radix Based on Bile Acid Homeostasis

Jiang

et al. 2022

Front. Pharmacol.

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Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.

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Physcion Induces Hemolysis and Premature Phosphatidylserine Externalization in Human Erythrocytes

Cited by 14 publications

References 32 publications

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

Molecular Mechanisms and Pathophysiological Significance of Eryptosis

Hepatotoxicity of the Major Anthraquinones Derived From Polygoni Multiflori Radix Based on Bile Acid Homeostasis

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