Antitumor potential of carrageenans from marine red algae.

Marine algae are abundant and inexhaustive sources of the bioactive compounds with the various benefits for human health. Among these substances an attention is given to the sulfated polysaccharides presented as the complexes of polymer macromolecules with excellent biological features including antioxidant, anti-inflammatory anticoagulant, antiviral, and immunomodulatory activities. In addition to the aforementioned properties there is a growing number of research results suggesting the bioactive sulfated polysaccharides such as carrageenan, fucoidan, laminarin, and others exert anticancer and antimetastatic properties. The present review contains the main results of experimental studies of the carrageenan anticancer activity including systemic and intracellular mechanisms of the antiproliferative influence. Relationships between structure, physico-chemical properties of carrageenan and their antitumor effects are described. There are data on the toxicology and pharmacokinetics of carrageenans as well as other aspects of their pharmacotherapeutic and pharmacoprophylactic influence that allow considering them as the potential anticancer agents.

Alkaloids of fascaplysin are effective conventional chemotherapeutic drugs, inhibiting the proliferation of C6 glioma cells and causing their death in vitro.

Glioblastoma multiforme is an invasive malignant glial brain tumor with a poor prognosis for patients. The primary reasons that lead to the development of treatment resistance are associated with tumor cells infiltrating the brain parenchyma and the specific properties of tumor stem cells. A crucial research area in medical science is the search for effective agents that are able to act on these targets. Fascaplysin alkaloids possess potent antitumor activity. Modern methods for the targeted delivery of drugs reveal extensive possibilities in terms of the clinical use of these compounds. The aim of the present study was to establish effective concentrations of fascaplysin that inhibit the growth and kill the cells of glial tumors, as well as to perform a comparative analysis of fascaplysin's effectiveness in relation to other chemotherapy drugs. C6 glioma cells were utilized as an optimal model of glioblastoma. It was established that fascaplysin at 0.5 µM has a strong cytotoxic effect, which is subsequently replaced by tumor cell death via apoptosis as the length of drug exposure time is increased. Fascaplysin kills glioma cells at a dose higher than 0.5 µM. The efficiency of fascaplysin was observed to significantly exceed that of temozolomide. Therefore, a significant feature of fascaplysin is its ability to inhibit the growth of and kill multipotent tumor cells.

Acute neuroinflammation provokes intracellular acidification in mouse hippocampus.

BACKGROUND: Maintaining pH levels within the physiological norm is an important component of brain homeostasis. However, in some pathological or physiological conditions, the capacity of the pH regulatory system could be overpowered by various factors resulting in a transient or permanent alteration in pH levels. Such changes are often observed in pathological conditions associated with neuroinflammation. We hypothesized that neuroinflammation itself is a factor affecting pH levels in neural tissue. To assess this hypothesis, we examined the effects of acute LPS-induced neuroinflammation on intra- and extracellular pH (pHi and pHo) levels in the CA1 region of mouse hippocampus. METHODS: Acute neuroinflammation was induced using two approaches: (1) in vivo by i.p. injections of LPS (5 mg/kg) and (2) in vitro by incubating hippocampal slices of naïve animals in the LPS-containing media (1 µg/mL, 1 h at 35 °C). Standard techniques were used to prepare hippocampal slices. pHi was measured using ratiometric pH-sensitive fluorescent dye BCECF-AM. pHo was assessed using calibrated pH-sensitive micropipettes. The presence of neuroinflammation was verified with immunohistochemistry (IL-1ß and Iba1) and ELISA (IL-1ß and TNF-α). RESULTS: A significant reduction of pHi was observed in the slices of the LPS-injected 3-month-old (LPS 7.13 ± 0.03; Sal 7.22 ± 0.03; p = 0.043, r = 0.43) and 19-month-old (LPS 6.78 ± 0.08; Sal 7.13 ± 0.03; p = 0.0001, r = 0.32) mice. In contrast, the levels of pHo within the slice, measured in 19-month-old animals, were not affected (LPS 7.27 ± 0.02; Sal 7.26 ± 0.02; p = 0.6, r = 0.13). A reduction of pHi was also observed in the LPS-treated slices during the interval 3.5-7 h after the LPS exposure (LPS 6.92 ± 0.07; Veh 7.28 ± 0.05; p = 0.0001, r = 0.46). CONCLUSIONS: Acute LPS-induced neuroinflammation results in a significant intracellular acidification of the CA1 neurons in mouse hippocampus, while the pHo remains largely unchanged. Such changes may represent a specific protective reaction of neural tissue in unfavorable external conditions or be a part of the pathological process.

Cerium binding activity of pectins isolated from the seagrasses Zostera marina and Phyllospadix iwatensis.

Cerium binding activity of three different water soluble pectin compounds of different origin was studied in a batch sorption system. The Langmuir, Freundlich and BET sorption models were adopted to describe the binding reactions between metal ions and pectin molecules. The Langmuir model provided the best fit. Within the pH range from 4.0 to 6.0, the largest amount of the cerium ions was bound by pectin isolated from the seagrass Phylospadix iwatensis in comparison to pectin extracted from the seagrass Zostera marina and pectin obtained from citrus peel (commercial grade). The Langmuir constants were also highest for the pectin samples isolated from the seagrass P. iwatensis. The results obtained from this study suggest that pectin is a prospective source for the development of radioisotope-removing pharmaceuticals.

Carrageenans as a new source of drugs with metal binding properties.

Carrageenans are abundant and safe non-starch polysaccharides exerting their biological effects in living organisms. Apart from their known pro-inflammation properties and some pharmacological activity, carrageenans can also strongly bind and hold metal ions. This property can be used for creation of the new drugs for elimination of metals from the body or targeted delivery of these metal ions for healing purposes. Metal binding activity of different carrageenans in aqueous solutions containing Y(3+) or Pb(2+) ions was studied in a batch sorption system. The metal uptake by carrageenans is not affected by the change of the pH within the range from 2.0 to 6.0. The rates and binding capacities of carrageenans regarding metal ions were evaluated. The Langmuir, Freundlich and BET sorption models were applied to describe the isotherms and constants, and the sorption isothermal data could be explained well by the Langmuir equation. The results obtained through the study suggest that kappa-, iota-, and lambda-carrageenans are favorable sorbents. The largest amount of Y(3+) and Pb(2+) ions are bound by iota-carrageenan. Therefore, it can be concluded that this type of polysaccharide is the more appropriate substance for elaboration of the drugs with high selective metal binding properties.

Cerium binding activity of different pectin compounds in aqueous solutions.

Cerium binding activity of different water soluble pectin compounds varying according to their degree of esterification and insoluble calcium pectate beads in aqueous solution was studied in a batch sorption system. The cerium uptake by all pectin compounds was highest within the pH range from 4.0 to 6.0. The binding capacities and rates of cerium ions by pectin compounds were evaluated. The Langmuir, Freundlich and BET sorption models were applied to describe the isotherms and constants. Sorption isothermal data could be well interpreted by the Langmuir equation. The results obtained through the study suggest that pectin compounds are favorable sorbents. The largest amount of cerium ions is bound by pectin with the degree of esterification close to zero. Therefore, it can be concluded that low esterified pectins are more effective substances for elimination of cerium ions from aqueous disposals.

Comparative equilibrium studies of sorption of Pb(II) ions by sodium and calcium alginate.

The absorption of Pb(II) ions from aqueous solution by different alginate compounds was studied in a batch sorption system. Water soluble sodium alginate and insoluble calcium alginate beads were investigated. The lead-binding capacity of both alginate compounds was highest within the pH range 6-8. The binding capacities and rates of Pb(II) ions by alginate compounds were evaluated. The Langmuir, Freundlich, and Bruneaur, Emmet and Teller (BET) sorption models were applied to describe the isotherms and isotherm constants. Sorption isothermal data could be well interpreted by the Langmuir model. The results obtained through the study suggest that alginate compounds are favorable sorbents. The largest amount of Pb(II) ions were bound by sodium alginate although the difference between two compounds was slight. Therefore, alginate substances may be considered as an alternative for sorption and removal of Pb(II) ions from wastewaters.

Equilibrium studies of sorption of lead(II) ions by different pectin compounds.

The adsorption of Pb(II) ions from aqueous solution by different pectin compounds was studied in a batch sorption system. Water-soluble low- and high-esterified pectins and insoluble calcium pectate beads were investigated. The lead-binding capacity of all pectin compounds was highest within the pH range from 7 to 8. The binding capacities and rates of Pb(II) ions by pectin compounds were evaluated. The Langmuir, Freundlich and BET sorption models were applied to describe the isotherms and isotherm constants. Sorption isothermal data could be well interpreted by the Langmuir model. These results obtained through the study suggest that pectin compounds are favorable sorbers. The largest amount of Pb(II) ions were bound by pectin with the low degree of esterfication. Therefore, pectin substances may be considered as perspective for sorption and removal of Pb(II) ions from wastewaters.

Lead absorption and excretion in rats given insoluble salts of pectin and alginate.

Exposure to environmental lead remains a widespread problem in most industrialized countries. Usage of modern agents purposed for elimination of heavy metals as well as for therapy and prevention of chronic poisoning does frequently result in toxic signs. Dietary nonstarch polysaccharides were suggested to be effective when used for this purpose. The present study was conducted to estimate metal binding capacity and effects of calcium salts of pectate and alginate on lead absorption, distribution, and removal with feces. Under in vitro conditions calcium alginate showed the highest lead-binding capacity in comparison with other agents studied. Metal binding capacity of calcium pectate was slightly lower. In rats simultaneous administration of lead acetate and suspensions containing calcium alginate or calcium pectate prevented metal absorption and significantly reduced lead accumulation in inner organs and femur. In experiments estimating lead removal from inner organs and femur in rats preliminary exposed to the heavy metal, calcium alginate and calcium pectate were the most effective agents studied in comparison with others, as indicated by reduced lead concentration in organs and femur as well as increased metal content in feces of laboratory animals. The results suggest that calcium pectate and calcium alginate may be considered perspective dietary compounds purposed for prevention and treatment of chronic lead poisoning.

The effects of low-esterified pectin on lead-induced thyroid injury in rats.

The main purpose of the study was to evaluate the effects of low-esterified pectin on lead-induced thyroid injury in rats. Animals were fed 100mg/kg of lead acetate through gavage for 3 weeks. After that, solution containing 50mg/kg of low-esterified pectin was administered through gavage for 2 weeks. At the end of experiment, the endpoints related to circulating thyroid hormone (serum thyroxine and triiodothyronine), thyroid gland histomorphology (thyroid follicle cross sectional area, epithelial height, follicle roundness or aspect ratio, and colloid/epithelial ratio), and thyroid gland weight were assessed. Administration of lead resulted in reduced blood hormone levels, decreased thyroid gland weight, and impaired alterations in histomorphology. At the end of experiment, thyroid gland weight and blood hormone level were increased because of additional administration of low-esterified pectin. Also, signs of improved thyroid histomorphology were registered. The results obtained indicate the beneficial effects of low-esterified pectin on lead-induced thyroid injury.