A Novel Antioxidant, EPC-K1, Stimulates Endothelial Nitric Oxide Production and Scavenges Hydroxyl Radicals

Takayama, Hiroo; Hamner, Chad E.; Caccitolo, James A.; Hisamochi, Kunikazu; Pearson, Paul J.; Schaff, Hartzell V.

doi:10.1253/circj.67.1046

Cited by 11 publications

(10 citation statements)

References 32 publications

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“…EPC-K1 is a complex of vitamin E and vitamin C and has demonstrated powerful antioxidant actions. Its protective effects against I/R damage in various organs have also been reported [13,14,15,16,17,18,19,20]. Based on these studies and the present results, we anticipate further development of EPC-K1 as a renoprotective therapeutic agent.…”

Section: Discussionsupporting

confidence: 82%

“…EPC-K1 is soluble in both water and lipids, and has a half-life of 32.2 min in blood plasma [13]. Previous studies have reported that EPC-K1 is effective in suppressing I/R injury in various tissues including the brain, heart, muscle, lung, and liver [13,14,15,16,17,18,19,20]. However, to the best of our knowledge, there are no published reports that EPC-K1 can attenuate renal I/R injury.…”

Section: Introductionmentioning

confidence: 99%

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The Antioxidant EPC-K1 Attenuates Renal Ischemia-Reperfusion Injury in a Rat Model

Yamamoto¹,

Hagiwara²,

Hidaka³

et al. 2011

Am J Nephrol

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Background: Acute kidney injury (AKI) occurs frequently in the intensive care unit. A primary cause is renal ischemia/reperfusion (I/R) injury, during which excess reactive oxygen species (ROS) are produced. ROS subsequently damage renal cells, leading to the development of AKI. Here, we investigated whether renal I/R injury could be attenuated by the antioxidant EPC-K1. Methods: We divided male Wistar rats into the following three groups: (1) a renal I/R group, (2) an EPC-K1 + renal I/R group and (3) a control group. Rats were sacrificed 24 h after treatment (I/R or sham). To measure oxidative stress in renal tissue, histological examinations were performed and serum levels of blood urea nitrogen (BUN) and creatinine were measured. The antioxidant action of EPC-K1 was also evaluated in RAW264.7 cells stimulated with antimycin A. Results: Serum BUN and creatinine levels were elevated in the I/R group; however, this increase was significantly attenuated by EPC-K1 in the EPC-K1 + I/R group. Renal tissue injury was also significantly lower in the EPC-K1 + I/R group compared with the I/R group. In vitro experiments showed that EPC-K1 significantly attenuated the generation of ROS induced by antimycin A. Conclusion: In our study, EPC-K1 was able to attenuate AKI due to renal I/R by reducing oxidative stress. These results suggest that EPC-K1 may be effective against various types of I/R injury.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

The Antioxidant EPC-K1 Attenuates Renal Ischemia-Reperfusion Injury in a Rat Model

Yamamoto¹,

Hagiwara²,

Hidaka³

et al. 2011

Am J Nephrol

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“…Furthermore, EPC-K1 modulates NF-kB and the glucocorticoid receptor via redox regulation [152,153], inhibits phospholipase A2 activity, and stimulates endothelial nitric oxide production leading to endothelium-dependent relaxation [154]. EPC-K1 prevents 6-hydroxydopamine-induced dopamine depletion in mouse striatum by increasing the activity of superoxide dismutase and catalase [155].…”

Section: Synthetic Tocopherol Derivatives With Increased Pharmacologimentioning

confidence: 99%

α‐Tocopheryl phosphate – An active lipid mediator?

Zingg

Meydani

Azzi

2010

Molecular Nutrition Food Res

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The vitamin E (alpha-tocopherol, alphaT) derivative, alpha-tocopheryl phosphate (alphaTP), is detectable in small amounts in plasma, tissues, and cultured cells. Studies done in vitro and in vivo suggest that alphaT can become phosphorylated and alphaTP dephosphorylated, suggesting the existence of enzyme(s) with alphaT kinase or alphaTP phosphatase activity, respectively. As a supplement in animal studies, alphaTP can reach plasma concentrations similar to alphaT and only a part is dephosphorylated; thus, alphaTP may act both as pro-vitamin E, but also as phosphorylated form of vitamin E with possibly novel regulatory activities. Many effects of alphaTP have been described: in the test tube alphaTP modulates the activity of several enzymes; in cell culture alphaTP affects proliferation, apoptosis, signal transduction, and gene expression; in animal studies alphaTP prevents atherosclerosis, ischemia/reperfusion injury, and induces hippocampal long-term potentiation. At the molecular level, alphaTP may act as a cofactor for enzymes, as an active lipid mediator similar to other phosphorylated lipids, or indirectly by altering membrane characteristics such as lipid rafts, fluidity, and curvature. In this review, the molecular and cellular activities of alphaTP are examined and the possible functions of alphaTP as a natural compound, cofactor and active lipid mediator involved in signal transduction and gene expression discussed.

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“…NOinduced neurotoxicity is reduced by EPC-K1 by preventing apoptosis and mitochondrial dysfunction in cerebellar granule cells (Wei et al, 1999a). EPC-K1 furthermore modulates NF-jB and the glucocorticoid receptor via redox regulation (Hirano et al, 1998;Okamoto et al, 1998), inhibits phospholipase A2 activity and stimulates endothelial nitric oxide production leading to endothelium-dependent relaxation (Takayama et al, 2003).…”

Section: Molecular and Cellular Effects Of A-tocopheryl Phosphate Andmentioning

confidence: 99%

Cellular, molecular and clinical aspects of vitamin E on atherosclerosis prevention

Munteanu¹,

Zingg

2007

Molecular Aspects of Medicine

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A Novel Antioxidant, EPC-K1, Stimulates Endothelial Nitric Oxide Production and Scavenges Hydroxyl Radicals

Cited by 11 publications

References 32 publications

The Antioxidant EPC-K1 Attenuates Renal Ischemia-Reperfusion Injury in a Rat Model

The Antioxidant EPC-K1 Attenuates Renal Ischemia-Reperfusion Injury in a Rat Model

α‐Tocopheryl phosphate – An active lipid mediator?

Cellular, molecular and clinical aspects of vitamin E on atherosclerosis prevention

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