Dextran

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Not to be confused with Dextrin.
Dextran
Identifiers
ChemSpider
  • none
ECHA InfoCard 100.029.694 Edit this at Wikidata
KEGG
Properties
H(C6H10O5)xOH
Molar mass Variable
Pharmacology
B05AA05 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Dextran is a complex branched glucan (polysaccharide made of many glucose molecules) composed of chains of varying lengths (from 3 to 2000 kilodaltons).

The straight chain consists of α-1,6 glycosidic linkages between glucose molecules, while branches begin from α-1,3 linkages.

Dextran was first discovered by Louis Pasteur as a microbial product in wine,[1] but mass production was only possible after the development by Allene Jeanes of a process using bacteria.[2] Dextran is now synthesized from sucrose by certain lactic acid bacteria, the best-known being Leuconostoc mesenteroides and Streptococcus mutans. Dental plaque is rich in dextrans.[3]

Medicinally it is used as an antithrombotic (antiplatelet), to reduce blood viscosity, and as a volume expander in hypovolaemia.[4] Dextran 70 is on the WHO Model List of Essential Medicines, the most important medications needed in a health system.[5]

Uses

Microsurgery

These agents are used commonly by microsurgeons to decrease vascular thrombosis. The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium, increasing their electronegativity and thus reducing erythrocyte aggregation and platelet adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor, thereby decreasing platelet function. Clots formed after administration of dextrans are more easily lysed due to an altered thrombus structure (more evenly distributed platelets with coarser fibrin[citation needed]). By inhibiting α-2 antiplasmin, dextran serves as a plasminogen activator, so possesses thrombolytic features.

Outside from these features, larger dextrans, which do not pass out of the vessels, are potent osmotic agents, thus have been used urgently to treat hypovolemia. The hemodilution caused by volume expansion with dextran use improves blood flow, thus further improving patency of microanastomoses and reducing thrombosis. Still, no difference has been detected in antithrombotic effectiveness in comparison of intra-arterial and intravenous administration of dextran.

Dextrans are available in multiple molecular weights ranging from 3,000 Da to 2,000,000 Da. The larger dextrans (>60,000 Da) are excreted poorly from the kidney, so remain in the blood for as long as weeks until they are metabolized. Consequently, they have prolonged antithrombotic and colloidal effects. In this family, dextran-40 (MW: 40,000 Da), has been the most popular member for anticoagulation therapy. Close to 70% of dextran-40 is excreted in urine within the first 24 hours after intravenous infusion, while the remaining 30% are retained for several more days.

Other medical uses

  • It is used in some eye drops as a lubricant.[6] and in certain intravenous fluids to solubilize other factors, such as iron (in a solution known as Iron Dextran).
  • Intravenous solutions with dextran function both as volume expanders and means of parenteral nutrition. Such a solution provides an osmotically neutral fluid that once in the body is digested by cells into glucose and free water. It is occasionally used to replace lost blood in emergency situations, when replacement blood is not available,[2][7] but must be used with caution as it does not provide necessary electrolytes and can cause hyponatremia or other electrolyte disturbances.
  • It also increases blood sugar levels.

Laboratory uses

  • Dextran is used in the osmotic stress technique for applying osmotic pressure to biological molecules.
  • It is also used in some size-exclusion chromatography matrices; an example is Sephadex.
  • Dextran has also been used in bead form to aid in bioreactor applications.
  • Dextran has been used in immobilization in biosensors.
  • Dextran preferentially binds to early endosomes; fluorescent-labelled dextran can be used to visualize these endosomes under a fluorescent microscope.
  • Dextran can be used as a stabilizing coating to protect metal nanoparticles from oxidation and improve biocompatibility.
  • Dextran coupled with a fluorescent molecule such as fluorescein isothiocyanate can be used to create concentration gradients of diffusible molecules for imaging and allow subsequent characterization of gradient slope.
  • Solutions of fluorescently-labelled dextran can be perfused through engineered vessels to analyze vascular permeability [8]
  • Dextran is used to make microcarriers for industrial cell culture

Side effects

Although relatively few side effects are associated with dextran use, these side effects can be very serious. These include anaphylaxis,[9] volume overload, pulmonary edema, cerebral edema, or platelet dysfunction.

An uncommon but significant complication of dextran osmotic effect is acute renal failure.[10] The pathogenesis of this renal failure is the subject of many debates with direct toxic effect on tubules and glomerulus versus intraluminal hyperviscosity being some of the proposed mechanisms.[citation needed] Patients with history of diabetes mellitus, renal insufficiency, or vascular disorders are most at risk. Brooks and others recommend the avoidance of dextran therapy in patients with chronic renal insufficiency.

See also

References

  1. ^ Pasteur, L. (1861). "On the viscous fermentation and the butyrous fermentation". Bull. Soc. Chim. Paris (in French). 11: 30–31. ISSN 0037-8968.
  2. ^ a b "Allene Rosalind Jeanes". Human Touch of Chemistry. Retrieved 13 May 2014.
  3. ^ Staat RH, Gawronski TH, Schachtele CF (1973). "Detection and preliminary studies on dextranase-producing microorganisms from human dental plaque". Infect. Immun. 8: 1009–16. PMC 422963. PMID 4594114.
  4. ^ Lewis, Sharon L. (2010). Medical Surgical Nursing (8th ed.). ISBN 978-0323079150.
  5. ^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
  6. ^ http://www.medicines.org.uk/EMC/medicine/74/SPC/Tears+Naturale/#CLINICAL_PARTS
  7. ^ Ogilvie, Marilyn; Harvey, Joy (2000). The biographical dictionary of women in science. New York: Routledge. p. 654. ISBN 0-415-92038-8.
  8. ^ Wang et al. "Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels", Lab on a Chip (journal), 2016, 16, 282
  9. ^ http://www.medicines.org.uk/emc/medicine/14139#UNDESIRABLE_EFFECTS
  10. ^ Feest, TG (1976). "Low molecular weight dextran: A continuing cause of acute renal failure". British Medical Journal. 2 (6047): 1300. doi:10.1136/bmj.2.6047.1300. PMC 1689992. PMID 1000202.

External links

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