Novel astaxanthin prodrug (CDX-085) attenuates thrombosis in a mouse model

Khan, Sanjoy K.; Maliński, Tadeusz; Mason, R. Preston; Kubant, Ruslan; Jacob, Robert F.; Fujioka, Kazutoshi; Denstaedt, Scott J.; King, Timothy J.; Jackson, Henry L.; Hieber, A. David; Lockwood, Samuel F.; Goodin, Thomas; Pashkow, Fredric J.; Bodary, Peter F.

doi:10.1016/j.thromres.2010.07.003

Cited by 50 publications

(32 citation statements)

References 31 publications

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“…Recently, developing therapeutic agents that improve NO bioavailability appears to be a hot research project both preclinically and clinically [45,46]. Published reports on the pleiotropic effects of statins have demonstrated improvements in eNOS activity [47,48] and endothelial function [49].…”

Section: Discussionmentioning

confidence: 99%

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

Liu¹,

Luo²,

Yang³

et al. 2015

Thrombosis Research

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Section: Discussionmentioning

confidence: 99%

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

Liu¹,

Luo²,

Yang³

et al. 2015

Thrombosis Research

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“…Also, our findings regarding the improved neurological outcome could be explained partly by beneficial effects of ATX through reducing oxidative stress. For example, ATX inhibits glutamate release, 18,25 reduces nuclear factor-kappa B translocation to the nucleus, 17 and inhibits platelet aggregation, 15 which has also been implicated in the pathophysiology of cerebral ischemia after SAH. 20 Last, the underlying molecular mechanisms of the antioxidant properties of ATX remain elusive.…”

mentioning

confidence: 99%

Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage

Zhang

Zhou

et al. 2014

JNS

102

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Object Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property. Methods Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation. Results It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH. Conclusions These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.

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“…The authors showed how ATX (by intracerebroventricular injection or oral administration) could significantly alleviate EBI in rat models by reducing brain oedema, BBB disruption, neural cells apoptosis, and neurological dysfunction. ATX may have pleiotropic effects through inhibition of glutamate release [133] by blocking inflammatory pathways (NF- κ B) [134], by limiting apoptosis and by platelets aggregation [135]. No side effects were reported following ATX use [136] and it may represent a new promising therapeutic option.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

To Look Beyond Vasospasm in Aneurysmal Subarachnoid Haemorrhage

Cossu

Messerer

Oddo

et al. 2014

BioMed Research International

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Delayed cerebral vasospasm has classically been considered the most important and treatable cause of mortality and morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Secondary ischemia (or delayed ischemic neurological deficit, DIND) has been shown to be the leading determinant of poor clinical outcome in patients with aSAH surviving the early phase and cerebral vasospasm has been attributed to being primarily responsible. Recently, various clinical trials aimed at treating vasospasm have produced disappointing results. DIND seems to have a multifactorial etiology and vasospasm may simply represent one contributing factor and not the major determinant. Increasing evidence shows that a series of early secondary cerebral insults may occur following aneurysm rupture (the so-called early brain injury). This further aggravates the initial insult and actually determines the functional outcome. A better understanding of these mechanisms and their prevention in the very early phase is needed to improve the prognosis. The aim of this review is to summarize the existing literature on this topic and so to illustrate how the presence of cerebral vasospasm may not necessarily be a prerequisite for DIND development. The various factors determining DIND that worsen functional outcome and prognosis are then discussed.

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Novel astaxanthin prodrug (CDX-085) attenuates thrombosis in a mouse model

Cited by 50 publications

References 31 publications

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage

To Look Beyond Vasospasm in Aneurysmal Subarachnoid Haemorrhage

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