Preclinical antitoxic properties of Spirulina (Arthrospira).

CONTEXT: Spirulina (Arthrospira) exerts a wide spectrum of pharmacological activities which are mainly attributed to its antioxidant effect. However, Spirulina has also been reported (both in preclinical and in clinical scenarios) to exhibit other bioactive effects, including an antitoxic potential. OBJECTIVE: We performed a systematic review of the literature, conducted in TOXNET, PubMed/MEDLINE, and Science Direct-Scopus; all available years were included. Searching criteria included the effects of Spirulina on experimental poisonings from arsenic, cadmium, carbon tetrachloride, deltamethrin, fluoride, hexachlorocyclohexane, iron, lead, lindane, and mercury. RESULTS: In all cases, it was established that the blue-green alga, and its isolated compounds, effectively counteracted these pollutants toxic effects on the exposed organisms. Some molecular mechanisms are proposed, although they have not been fully elucidated yet. CONCLUSION: Spirulina could be a useful coadjuvant agent within clinical practice for treatment of these or other pollutants poisonings.

Prevention of Aflatoxin B1-Induced DNA Breaks by ß-D-Glucan.

Aflatoxins are a group of naturally-occurring carcinogens that are known to contaminate different human and animal foodstuffs. Aflatoxin B1 (AFB1) is the most genotoxic hepatocarcinogenic compound of all of the aflatoxins. In this report, we explore the capacity of ß-D-glucan (Glu) to reduce the DNA damage induced by AFB1 in mouse hepatocytes. For this purpose, we applied the comet assay to groups of animals that were first administered Glu in three doses (100, 400 and 700 mg/kg bw, respectively) and, 20 min later, 1.0 mg/kg of AFB1. Liver cells were obtained at 4, 10 and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB1 with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The data suggested the formation of a supramolecular complex between AFB1 and ß-D-glucan.

Metals and nonsteroidal anti-inflammatory pharmaceuticals drugs present in water from Madín Reservoir (Mexico) induce oxidative stress in gill, blood, and muscle of common carp (Cyprinus carpio).

Many toxic xenobiotics that enter the aquatic environment exert their effects through redox cycling. Oxidative stress, which incorporates both oxidative damage and antioxidant defenses, is a common effect induced in organisms exposed to xenobiotics in their environment. The results of the present study aimed to determine the oxidative stress induced in the common carp Cyprinus carpio by contaminants [metals and nonsteroidal anti-inflammatory drugs (NSAIDs)] present in Madín Reservoir. Five sampling stations (SSs), considered to have the most problems due to discharges, were selected. Carp were exposed to water from each SS for 96 h, and the following biomarkers were evaluated in gill, blood, and muscle: hydroperoxide content, lipid peroxidation, protein carbonyl content, and the activity of antioxidant enzymes superoxide dismutase and catalase. Results show that contaminants (metals and NSAIDs) present in water from the different SSs induce oxidative stress. Thus, water in this reservoir is contaminated with xenobiotics that are hazardous to C. carpio, a species consumed by the local human population.

Spirulina (arthrospira) protects against valproic acid-induced neural tube defects in mice.

Valproic acid (VPA) is a potent inducer of neural tube defects in human and mouse, its teratogenicity is associated with its potential to generation of free radicals and increase oxidative stress. Furthermore, spirulina (SP) has shown pharmacological properties against teratogenicity, which are attributed to its antioxidant potential. Accordingly, the present study was performed to investigate the influence of SP on the teratogenicity of VPA in imprinting control region mice and the possible mechanisms of action. VPA (sodium valproate) was administered intraperitoneally to mice on gestation day (GD) 8 at a dose of 600 mg/kg. SP was given orally at 125, 250, and 500 mg/kg daily from GD0 through GD18. The most common finding in fetuses with VPA exposure was exencephaly. SP decreased the incidence of this and other malformations and increased levels of superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, these results illustrate the protective action of SP through its antioxidant activity against VPA-induced teratogenicity.

Spirulina (Arthrospira) protects against cadmium-induced teratogenic damage in mice.

The role of Spirulina (Arthrospira) in preventing cadmium (Cd) teratogenicity in ICR mice was studied. Cd was administered intraperitoneally to female mice at 1.5 mg/kg on gestation day (GD)-7, and Spirulina was given by peroral (intragastric) administration at 62.5, 125, 250, or 500 mg/kg from GD-0 through GD-17 (the day when animals were sacrificed). Because among the mechanisms suggested to account for reproductive damage are oxidative stress and lipoperoxidation, embryonic hydroperoxides were also determined. Treatment with Spirulina at the three highest doses significantly decreased the frequency of fetuses with exencephaly, micrognathia, and skeletal abnormalities induced by Cd. Furthermore, Spirulina treatment significantly and dose-dependently decreased lipid peroxidation, which was dramatically increased by administration of the metal. The results of the present study clearly point to the therapeutic potential of Spirulina in Cd-induced teratogenicity and probably through its antioxidant activity.

Quercetin and naringenin reduce abnormal development of mouse embryos produced by hydroxyurea.

OBJECTIVES: There is limited evidence about the impact of quercetin and naringenin on embryonic development. The purpose of this work was to evaluate in vitro their direct teratogenic potential as well as their protective activity against teratogenesis mediated by oxidative damage on mouse embryos. METHODS: Quercetin and naringenin toxicity on whole mouse cultured embryos, as well as their ability to protect embryos against hydroxyurea-induced insult were evaluated. KEY FINDINGS: Quercetin 100 microm and naringenin 300 microm produced significant reduction of developmental and growth parameters, in comparison with those of the control group. Embryos exposed to the concurrent administration of quercetin or naringenin with hydroxyurea (2 microm, 2 h) were significantly protected from growth and developmental retardation, and abnormalities induced by hydroxyurea. Interestingly, embryos exposed to hydroxyurea and dimethyl sulfoxide 0.1%, the vehicle employed to dissolve flavonoids, also showed significant damage amelioration. CONCLUSIONS: These results indicate that quercetin and naringenin have not only a minor toxic effect on development, but also a protective effect against hydroxyurea-induced embryonic damage.

Antigenotoxic studies of different substances to reduce the DNA damage induced by aflatoxin B(1) and ochratoxin A.

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB(1) and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins.

Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to alpha-asarone.

The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases.

Effects of dimethylsulphoxide on mice arsenite-induced dysmorphogenesis in embryo culture and cytotoxicity in embryo cells.

Dimethylsulphoxide (DMSO) is a widely used vehicle for water insoluble compounds in experimental studies. Nevertheless, little is known about its potential impact on dysmorphogenesis caused by reactive oxygen species (ROS). In order to evaluate if DMSO at concentrations used as vehicle can alter in vitro sodium arsenite (Asi) teratogenicity and cytotoxicity, mouse embryos with 4-5 somites were grown for 48 h in Asi 0.4 and 4 microM, with and without 0.1% DMSO (v/v). Also embryonic mesenchymal cell were cultured, using mesenchymal mouse embryo cells obtained from gestation day 11 and treated with DMSO 0.1%, 0.2% and 0.5% (v/v) 15 min before Asi was added at final concentrations of 0.4 and 4 microM. Cytotoxicity and intracellular ROS production, were evaluated with MTT and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), respectively. Results indicated that Asi produced growth retardation and abnormal development. Main malformations involved neural tube closure defects, abnormal rotation and optic vesicle defects among others. Co-treatment with DMSO partially reduced neural tube defects as well as facial dysmophology. Asi reduced cell viability inversely to the level of ROS production, and DMSO returned cellular viability to control values by reducing ROS intracellular production. In summary, the protective effect observed for DMSO appeared to reflect free radical scavenger properties, though other mechanisms independent to ROS production may have also been involved.