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. 2021 Feb 18;13(2):160.
doi: 10.3390/toxins13020160.

Attempt to Develop Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom Injection

Akihiko Yamamoto  1 , Takashi Ito  2 , Toru Hifumi  3
Affiliations

Attempt to Develop Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom Injection

Akihiko Yamamoto et al. Toxins (Basel). .

Abstract

Disseminated intravascular coagulation, a severe clinical condition caused by an underlying disease, involves a markedly continuous and widespread activation of coagulation in the circulating blood and the formation of numerous microvascular thrombi. A snakebite, including that of the Yamakagashi (Rhabdophis tigrinus), demonstrates this clinical condition. Thus, an animal model using Yamakagashi venom was constructed. Yamakagashi venom was administered to rats, and its lethality and the changes in blood coagulation factors were detected after venom injection. When 300 μg venom was intramuscularly administered to 12-week-old rats, (1) they exhibited hematuria with plasma hemolysis and died within 48 h; (2) Thrombocytopenia in the blood was observed in the rats; (3) irreversible prolongation of prothrombin time in the plasma to the measurement limit occurred; (4) fibrinogen concentration in the plasma irreversibly decreased below the measurement limit; and (5) A transient increase in the plasma concentration of D-dimer was observed. In this model, a fixed amount of Rhabdophis tigrinus venom injection resulted in the clinical symptom similar to the human pathology with snakebite. The use of the rat model is very effective in validating the therapeutic effect of human disseminated intravascular coagulation condition due to snakebite.

Keywords: D-dimer; Yamakagashi (Rhabdophis tigrinus) venom; anti-Yamakagashi equine antibody; lethality; rat disseminated intravascular coagulation model; thrombocytopenia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lethal dose of Yamakagashi venom. Survival time after intravenous (IV) injection of 150 μg venom (◆). Survival time after IM administration of 150, 200, and 250 μg venom (■). Survival time after intramuscular (IM) administration of 300 μg venom (●). Survival time of rt intramuscularly administered 300 μg venom and antivenom 2 h after venom administration (▲). Each group consists of 3 rats.
Figure 2
Figure 2
Time course of platelet count after IM administration of Yamakagashi venom. (a) 300 μg venom was intramuscularly administered to rats. Closed circle indicates the mean platelet counts. (b) Platelet counts of blood from rat intramuscularly administered 150 μg venom (●), 200 μg venom (◆), and 250 μg venom (▲). (c) Platelet counts of blood from rat intramuscularly administered 300 μg venom and antivenom 2 h after venom administration (◆). Each group consists of 3 rats. Values were mean ± SD.
Figure 3
Figure 3
Time course of PT after IM administration of Yamakagashi venom. (a) 300 μg venom was intramuscularly administered to rats. Closed circle indicates the PT; (b) PT of plasma from rat intramuscularly administered 150 μg venom (●), 200 μg venom (◆), and 250 μg venom (▲); (c) PT of plasma from rat intramuscularly administered 300 μg venom and antivenom 2 h after venom administration (●). Each group consists of 3 rats. Values were mean ± SD.
Figure 4
Figure 4
Time course of fibrinogen (FIB) concentration after IM administration of Yamakagashi venom. (a) 300 μg venom was intramuscularly administered to rats. Closed circle indicates the mean FIB concentration; (b) FIB concentration of plasma from rat intramuscularly administered 150 μg venom (●), 200 μg venom (◆), and 250 μg venom (▲); (c) FIB concentration of plasma from rat intramuscularly administered 300 μg venom and antivenom 2 h after venom administration (◆). Each group consists of 3 rats. Values were mean ± SD.
Figure 5
Figure 5
Time course of D-dimer in plasma after IM administration of Yamakagashi venom (a) 300 μg venom was intramuscularly administered to rats. Closed circle indicates the mean D-dimer concentration; (b) D-dimer concentration of plasma from rat intramuscularly administered 300 μg venom and antivenom 2 h after venom administration (●). Each group consists of 3 rats. Values were mean ± SD.
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