Rats are unsuited model animals for Dextran

Rats are unsuited model animals for Dextran investigations due to adverse reactions to dextran not seen in higher mammals.

Delayed hypersensitivity of most strains of rat to dextrans, mannan, ovomucoid and some other polysaccharides has been well documented since the early 1950s.  The reaction is characterized by direct histamine release from mast cells and , in the case of neutral clinical dextrans, such direct histamine release only occurs in rats, not in other rodents or other mammals, including man.  Almost all strains of rat exhibit this form of hypersensitivity to dextran with the exception of some inbred strains of Whistar rats expressing the recessive Non-Reacting (NR) genetic trait, usually denoted as  Whistar–NR or NELP rats.

Since direct histamine release will induce local edema, and an increase in tissue wet/dry ratio, it is evident that  any study comparing effects of fluids containing dextran  and other non-dextran solutions in the rat model will be invalidated by edema formation in the dextran group unless the animals used are certified inbred Non-Reactor strains. Some flexibility may be acceptable in comparative studies on other drugs in which both or all comparative groups of rats receive the same low dose of dextran and wet/dry ratios (or other parameters of edema) are not used as end-points in the study, although the indirect effects of edema formation on other parameters and end-points should always be borne in mind. Note also that some drugs, such as insulin, tend to enhance this specific hypersensitivity, whereas others, including glucose have the opposite effect. In regards to dextran, the molecular configuration/branching and molecular weight also influence the degree of hypersensitivity induced. A linear dextran with less than 5% 1-3, or 1-4 glucosidic branching (as produced by fermentation from Leuconostoc mesenteroides strain B512, as used clinically, is four times less likely to induce histamine release in susceptible rats than the branched forms of natural dextrans produced by wild strains of Leuconostoc. One should also note that very low mol wt dextrans ( < 2500 Da) do not normally seem to induce this type of hypersensitivity reaction in rats.

A selection of abstracts which illustrates some of these typical problems in using rats for research on dextrans can be found below.

Please note that the above remarks primarily apply to neutral dextrans (not to charged substituted dextrans), with and an average weight molecular within the “clinical” range (< 100 kDa)

Reference List

Enhancement of the anaphylactoid reaction in rats by phenylalanine enamine.
West GB.
Int Arch Allergy Appl Immunol. 1983;71(3):282-4.

Susceptibility of two colonies of Wistar rats to inflammation, with particular reference to delayed hypersensitivity.
de Brito FB, Hanahoe TH.
Int Arch Allergy Appl Immunol. 1983;72(2):164-9.

Delayed hypersensitivity reactions in rats and their response to clinical dextran.
de Brito FB, Hanahoe TH, Shah P, West GB.
Int Arch Allergy Appl Immunol. 1982;69(2):109-12.          

Enhancement of the anaphylactoid reaction in rats by salicylates.
West GB.
Int Arch Allergy Appl Immunol. 1982;68(2):185-7.

Dextran anaphylactoid reaction in Sprague-Dawley CFY rats.
Blazso G, Koltai M, Ottlecz A, Minker E.
Acta Physiol Acad Sci Hung. 1979;54(3):281-6.  

Anaphylactoid responses in rats.
West GB.
Int Arch Allergy Appl Immunol. 1977;55(1-6):542-5.         

A comparison of the anaphylactoid actions of a synthetic linear dextran and a natural branched dextran.
Delitheos AK, Hanahoe TH, West GB.
Int Arch Allergy Appl Immunol. 1976;50(4):436-45.          

Differences in responses between  rat strains and colonies
J.M. Harris
Food and cosmetics Toxicology Volume 3, 1965, Pages 199-202

Toxicity of Dextran in Rats
T. EDLUND, B. LÖFGREN & L. VÄLI
Nature 170, 125 (19 July 1952); doi:10.1038/170125a0