Antiviral activity of a carrageenan from Gigartina skottsbergii against intraperitoneal murine herpes simplex virus infection.
The partially cyclized mu/nu-carrageenan 1C3, isolated from the red seaweed Gigartina skottsbergii, was previously shown to be a potent inhibitor of the in vitro replication of Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Here the protective effect of 1C3 in a murine model of intraperitoneal ( i. p.) HSV-1 infection was evaluated. OF1 mice were i. p. infected with 5 x 10 (5) PFU of HSV-1 KOS strain, and the effects of different treatments with 1C3 were studied. When 30 mg/kg of body weight of 1C3 was administered by the i. p. route immediately after HSV-1 infection, 87.5 % survival of the animals was achieved (p < 0.005), associated with a delay in the mean day of death in 1C3-treated non-surviving mice. Animal survival was not improved when multiple doses of 1C3 were also given in the period 1 - 48 h post-infection, and no protection was afforded when treatment was started after 24 h of infection. When virus and compound were injected by different routes, i. p. and intravenous ( i. v.), respectively, a still significant protection was achieved (40 % survival, p < 0.05). No toxicity of 1C3 for the animals was recorded. The pharmacokinetic properties were analyzed after injection of 1C3 into the tail vein by monitoring of [ (3)H]-1C3 in plasma and organs and by a bioassay of the anti-HSV-1 activity remaining in serum after non-radioactive 1C3 inoculation. A very rapid disappearance of the compound from the blood was observed since only 5.9 - 0.9 % of the radioactivity of the initially administered [ (3)H]-1C3 appeared in the plasma between 5-300 minutes after administration. A transient peak of radioactivity was detected in the kidney 15 minutes after inoculation. The bioassay confirms the presence of the compound circulating in a biologically active form up to 1 hour after injection.
Pujol
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Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Piso 4, Ciudad Universitaria C1428BGA Buenos Aires, Argentina. capujol@qb.fcen.uba.ar
Scolaro
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Ciancia
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Matulewicz
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Cerezo
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Damonte
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D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D002351:Carrageenan / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use; D000461:Rhodophyta / Q000737:chemistry*; D014018:Tissue Distribution
D000998:Antiviral Agents; D028321:Plant Preparations; D002351:Carrageenan