Transcrocetinate sodium

Crocetin is difficult to solubilize. Sodium crocetinate, formed by reacting crocetin with sodium hydroxide, appears in several isomeric forms.
We can achieve Trans sodium crocetinate by reacting Crocus sativus (Saffron) with Sodium hydroxide and the extraction of salt of Crocetin isomer.
The sodium salt of crocetin called, transcrocetinate sodium (also known as trans sodium crocetinate or TSC) has shown that it will cause to increase the rate of movement of oxygen from red blood cells into hypoxic (oxygen-starved) tissues. Tran sodium crocetinate belongs to a group of substances which are known as bipolar trans carotenoid salts, they are the subclass of oxygen diffusion-enhancing compounds. TSC is the first one which got discovered.

Transcrocetinate sodium

In below you can find some summary of various studies on TSC:

Trans sodium crocetinate (TSC) is a bipolar synthetic carotenoid and has been designed to increase the oxygenation of hypoxic tissues. TSC will increase the diffusivity of oxygen (the ability of oxygen to move from a higher to a lower concentration).  which is the primary mechanism by that TSC can exerts its pharma codynamic effects, it’s also been shown in models of ischemic injury where TSC cause the increase the concenteration of oxygen tissue.

John L. Gainer and colleagues have been studied the effects of transcrocetinate sodium in animal. They found out that the drug could reverse the potentially fatal decrease in blood pressure in case of severe loss of blood which cause hemorrhage, and thereby cause survival. [11]
Early investigations of transcrocetinate sodium suggested that it did have a  potential applications in battlefield medicine, specifically in treatment of the many combat casualties with hemorrhagic shock.[8][11] Additional studies, on animal models and in clinical trials in humans, have been shown that transcrocetinate sodium might prove beneficial in the treatment of a variety of conditions associated with hypoxia and ischemia (a lack of oxygen reaching the tissues, usually due to a disruption in the circulatory system), including cancer, myocardial infarction (heart attack), and stroke.
Transcrocetinate sodium has shown promise of effectiveness in restoring tissue oxygen levels and improving the ability to walk in a clinical trial of patients with peripheral artery disease (PAD) [13] in which reduced delivery of oxygen-rich blood to tissues can cause severe leg pain and impair mobility. The drug has also been under investigation in a clinical trial for potential use as a radiosensitizer, increasing the susceptibility of hypoxic cancer cells to radiation therapy, in some patients with a form of brain cancer known as glioblastoma. [14]

Similar to other oxygen diffusion-enhancing compounds, transcrocetinate sodium appears to improve oxygenation in hypoxic tissues by exerting hydrophobic effects on water molecules in blood plasma and thereby increasing the hydrogen bonding between the water molecules. [15] This in turn causes the overall organization of water molecules in plasma to become more structured, which facilitates the diffusion of oxygen through plasma and promotes the movement of oxygen into tissues.
Trans-crocetin has been found to act as an NMDA receptor antagonist with high affinity, and has been implicated in the psycho activity of Saffron.

In other study of Trans Sodium Crocetinate A high-fat diet used to induce obesity in mice. This model should be very similar to human obesity because of excessive high-fat diet is a major cause for obesity and hyperlipidemia in humans (Kopelman, 2000) The result clearly shown that 0.14 mg/kg TSC given under a bolus– infusion–bolus regimen improved neurological outcomes after transient focal brain ischemia. TSC been shown to improve neurological outcomes after ischemic brain injury in young adult rats and rabbits (Lapchak, 2010; Manabe et al., 2010). This study provides initial evidence that TSC provides neuroprotection in animals with pathological conditions, such as obesity and hyperlipidemia, which often exist in patients suffering from ischemic stroke (Iso et al., 1989; Balci et al., 2011).

Some other studies show TSC increased mean arterial blood pressure from a value (immediately after hemorrhage) of 35 mm Hg to a value of 75 mm Hg, and all treated animals survived. In contrast, blood pressure in control animals decreased, with most dying soon after the hemorrhage. TSC also lessened the tachycardia which resulted from the hemorrhage. Blood pH did not decrease as much when TSC was given, and plasma lactate levels were greatly reduced.
 It would appear that TSC is a promising initial treatment for hemorrhagic shock.
 Other Studies suggest TSC is a promising drug candidate to treat ischemic stroke (AIS), we tested the hypothesis that TSC may be neuroprotective following cerebral ischemia using a rabbit small clot embolic stroke model (RSCEM) using clinical rating scores as the endpoint.  This study suggests that TSC may be used for the treatment of AIS either alone or when administered before or concomitant with tPA to improve clinical rating scores with a therapeutic window for TSC therapy up to 3 h in rabbits. Moreover, it appears that TSC can be administered with tPA, since the combination did not result in any significant change in intracerebral hemorrhage.

Also Trans?sodium crocetinate (TSC), the isomer of the carotenoid compound crocetin, is found markedly to increase survival in hemorrhagic shock subsequent to 50–60% blood loss, mainly via restored resting oxygen consumption (VO2), blood pressure and heart rate. The proposed mechanism is that TSC increases oxygen diffusivity, and thus availability, in plasma. If this were found to be a prominent feature in the oxygen transfer from blood to skeletal muscle fiber mitochondria, increased VO2 during exercise would be expected because of reduced partial pressure of venous oxygen (increased utilization), which we aimed to elucidate in this study. Male Sprague?Dawley rats were intravenously injected with 0.3 mL kg−1 TSC (40 µg mL−1) or placebo and immediately thereafter tested on a ramped treadmill test protocol. Rats were introduced to the experimental protocols beforehand. Administration of TSC had a neutral effect on submaximal and maximal VO2(VO2max) as well as running performance measured as maximal running time and maximal aerobic running velocity. Thus, in this study we cannot report any effects of TSC on steady?state submaximal VO2 or VO2max at exhaustive exercise.



All these studies shown that TSC can be very effective on curing so many cancer types also have a very large effect on Ischemia.

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  • Sheehan, J., Cifarelli, C.P., Dassoulas, K., Olson, C., Rainey, J., etal., 2010. Trans-sodium crocetinate enhancing survivaland glioma response on magnetic resonance imaging to radiation and temozolomide.J. Neurosurg. 113,234–239

  • Sheehan, J., Ionescu, A., Pouratian, N., Hamilton,D.K., Schlesinger, D., etal., 2008.Use of trans sodium crocetinate for sensitizing glioblastoma multi formetoradiation: laboratoryinvestigation.J.Neurosurg.108,972–978.

  • Sheehan, J., Sherman, J., Cifarelli, C., Jagannathan, J., Dassoulas,K., et al.,2009.Effec to trans sodium crocetinate on brain tumor oxygenation. Laboratory investigation.J. Neurosurg.111, 226–229.

  •  Singhal, A.B., 2007.Are view of oxygen therapy ini schemic stroke.Neurol.Res.29,173–183.

  •  Stennett, A.K., Dempsey, G.L., Gainer, J.L., 2006.Trans-sodium crocetinate and diffusion enhancement. Phys.Chem. B110, 18078–18080.

  • Stennett, A.K., Murray, R.J., Roy, J.W., Gainer, J.L., 2007.Trans- sodium crocetinate and hemorrhagic shock. Shock28, 339–344.

  • Wang, Y., Bontempi, B., Hong, S.M., Mehta, K., Weinstein, P.R., etal., 2008. A comprehensive analysis of gait impairment after experimental stroke and the therapeutic effect of environmental enrichment in rats.J. Cereb. Blood Flow Metab.28,1936–1950.

  • Yamaguchi, K., Nguyen-Phu, D., Scheid, P., Piiper, J.,1985. Kinetics of O2 uptake and release by humanery throcytes studied bya stopped-flow technique.J.Appl.Physiol.58,1215–1224.

  • Huxley, V.H., Kutchai, H., 1981.Theeffectoftheredcell membrane and adiffusion boundary layer on the rate of oxygen up take by humanery throcytes. J. Physiol. 316,75–83.

  • Huxley, V.H., Kutchai, H., 1983.Effect of diffusion boundary layers on the initial up take of O2 by red cells. The or versus experiment. Microvasc. Res. 26,89–107.

  • Laidig, K.E., Gainer, J.L., Daggett, V., 1998.Altering diffusivity in biological solutions through modification of solution structure and dynamics. J. Am.Chem.Soc.120,9394–9395.

  • Lapchack, P.A., 2012. A clinically relevant rabbit embolic stroke model for acute ischemic stroke therapy development: mechanisms and targets. In: Lapchack, P.A., Zhang,J.H.(Eds.), Translational Stroke Research: From Target Selection to Clinical Trials.Springer,pp.541–584.

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