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1.
Mar Drugs ; 16(11)2018 Oct 27.
Article in English | MEDLINE | ID: mdl-30373238

ABSTRACT

Worldwide, snakebites have serious implications for human health. The administration of antivenom is the official treatment used to reverse the toxic activities of envenomation. However, this therapy is not efficient to treat the local effects, leading to the amputation or deformity of affected limbs. As such, alternative treatments are needed. Here, we analyze the ability of a polysaccharide from the green marine alga Gayralia oxysperma (Go3) to inhibit the effects of venom from Bothrops jararaca and Lachesis muta. B. jararaca or L. muta venoms were incubated together with sulfated heterorhamnans from Go3, and the in vitro (coagulation, proteolytic, and hemolytic) and in vivo (hemorrhagic, myotoxic, edematogenic, and lethal) activities of venoms were assessed. Additionally, Go3 was injected before and after the injection of venoms, and the toxic activities were further tested. When incubated with the venoms, Go3 inhibited all activities, though results varied with different potencies. Moreover, Go3 neutralized hemorrhagic, myotoxic, and edematogenic activities when injected before or after injection with B. jararaca and L. muta venom. Go3 also blocked the coagulation of plasma in mice caused by the venoms in an ex vivo test. Therefore, Go3 has the potential to be used as antivenom for B. jararaca and L. muta bites, notably exhibiting higher efficacy on L. muta venom.


Subject(s)
Antivenins/pharmacology , Aquatic Organisms/chemistry , Chlorophyta/chemistry , Deoxy Sugars/pharmacology , Mannans/pharmacology , Snake Bites/drug therapy , Animals , Antivenins/isolation & purification , Antivenins/therapeutic use , Blood Coagulation/drug effects , Bothrops , Crotalid Venoms/antagonists & inhibitors , Crotalid Venoms/pharmacology , Deoxy Sugars/isolation & purification , Deoxy Sugars/therapeutic use , Disease Models, Animal , Hemolysis/drug effects , Humans , Mannans/isolation & purification , Mannans/therapeutic use , Mice , Mice, Inbred BALB C , Snake Bites/blood
2.
Mar Biotechnol (NY) ; 18(6): 619-629, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27888371

ABSTRACT

Snakebite is a serious occupational hazard affecting mainly rural populations of tropical and subtropical developing countries. Lachesis muta (Bushmaster) bites are extremely serious but are rarely reported in the literature. Bushmaster envenomings are characterized by intense local pain, edema, neurotoxicity, hypotension, local hemorrhage, and dramatic systemic alterations. Antivenom treatment has regularly been used for more than a century; however, it fails to neutralize local tissue damage and hemorrhage, leading to morbidity or disabilities in victims. Thus, the production and clinical use of antivenom must be improved. The present work characterizes, for the first time, a sulfated polysaccharide from the red seaweed, Laurencia aldingensis, including its neutralizing effect on some toxic activities of L. muta venom. Chemical and spectroscopic analyses showed that L. aldingensis produces sulfated agarans with the A-units partially C-2 sulfated or 6-O-methoxylated presetting the B-units in the cyclized (3,6-anhydro-α-L-galactose) or in the non-cyclized form (α-L-galactose). The latter is significantly substituted by sulfate groups on C-6. In vitro and in vivo assays showed that this sulfated agaran inhibited hemolysis, coagulation, proteolysis, edema, and hemorrhage of L. muta venom. Neutralization of hemorrhagic activity was also observed when the agaran was administered by different routes and after or before the venom injection. Furthermore, the agaran blocked the edema caused by a phospholipase A2 isolated from the L. muta venom. Experimental evidence therefore indicates that the sulfated agaran of L. aldingensis has potential to aid antivenom therapy of accidents caused by L. muta venom and may help to develop more effective antivenom treatments of snake bites in general.


Subject(s)
Antivenins/pharmacology , Edema/prevention & control , Laurencia/chemistry , Polysaccharides/pharmacology , Snake Bites/drug therapy , Viper Venoms/antagonists & inhibitors , Animals , Antivenins/chemistry , Antivenins/isolation & purification , Blood Coagulation/drug effects , Edema/chemically induced , Hemolysis/drug effects , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Humans , Mice , Phospholipases A2/administration & dosage , Plant Extracts/chemistry , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Proteolysis/drug effects , Seaweed , Snake Bites/physiopathology , Sulfates , Viper Venoms/toxicity , Viperidae
3.
Mar Drugs ; 13(6): 3761-75, 2015 Jun 11.
Article in English | MEDLINE | ID: mdl-26110897

ABSTRACT

In Brazil, snakebites are a public health problem and accidents caused by Lachesis muta have the highest mortality index. Envenomation by L. muta is characterized by systemic (hypotension, bleeding and renal failure) and local effects (necrosis, pain and edema). The treatment to reverse the evolution of all the toxic effects is performed by injection of antivenom. However, such therapy does not effectively neutralize tissue damage or any other local effect, since in most cases victims delay seeking appropriate medical care. In this way, alternative therapies are in demand, and molecules from natural sources have been exhaustively tested. In this paper, we analyzed the inhibitory effect of a sulfated galactan obtained from the red seaweed Palisada flagellifera against some toxic activities of L. muta venom. Incubation of sulfated galactan with venom resulted in inhibition of hemolysis, coagulation, proteolysis, edema and hemorrhage. Neutralization of hemorrhage was also observed when the galactan was administered after or before the venom injection; thus mimicking a real in vivo situation. Moreover, the galactan blocked the edema caused by a phospholipase A2 isolated from the same venom. Therefore, the galactan from P. flagellifera may represent a promising tool to treat envenomation by L. muta as a coadjuvant for the conventional antivenom.


Subject(s)
Antivenins/pharmacology , Galactans/pharmacology , Rhodophyta/chemistry , Viper Venoms/antagonists & inhibitors , Animals , Antivenins/isolation & purification , Brazil , Galactans/isolation & purification , Mice , Mice, Inbred BALB C , Phospholipases A2/metabolism , Snake Bites/drug therapy , Viper Venoms/toxicity , Viperidae
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