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Globally, research is being conducted focusing on new biologically active substances and technologies for their application in various sectors, in the hope that their biological and medical applications will be widely used in the next decade. The introduction of therapeutic agents of biological origin isolated from certain species of bacteria and algae and their potential for cancer treatment is based on their lower toxicity and hence greater safety compared to synthetic pharmaceuticals. In this respect, the potential of microbial producers and microalgae is enormous. Among the biologically active components isolated from algae of the greatest importance for biology and medicine are complex polysaccharides, as well as some pigments. In the present work, the antitumour properties of two fractions of polysaccharides from the red microalgae Porphyridium cruentum were observed by determining their effect on cell viability of four different cell lines. New data from the study indicate that samples treated with P. cruentum polysaccharide have significant and dose-dependent antiproliferative and cytotoxic effects. Changes in nuclear morphology in MCF-7 tumour cells induced by polysaccharide treatment, including chromatin condensation, nucleus fragmentation, and apoptotic body formation, have been demonstrated. Polysaccharides show obvious pharmacological effects in the treatment of tumour cells without side effects.

Lead (Pb) is a highly toxic heavy metal that has deleterious effects on the central nervous system. This study aimed to investigate the effects of salinomycin (Sal) and deferiprone (DFP) on brain morphology and on the content of some essential elements in Pb-exposed mice. Adult male Institute of Cancer Research (ICR) mice were exposed to a daily dose of 80 mg/kg body weight ( b.w.) Pb(II) nitrate for 14 days and subsequently treated with Sal (16 mg/kg b.w.) or DFP (19 mg/kg b.w.) for another 14 days. At the end of the experimental protocol, the brains were processed for histological and inductively coupled plasma mass spectrometry (ICP-MS) analyses. Pb exposure resulted in a 50-fold increase in Pb concentration, compared with controls. Magnesium (Mg) and phosphorus (P) were also significantly increased by 22.22% and 17.92%, respectively. The histological analysis of Pb-exposed mice revealed brain pathological changes with features of neuronal necrosis. Brain Pb level remained significantly elevated in Sal- and DFP-administered groups (37-fold and 50-fold, respectively), compared with untreated controls. Treatment with Sal significantly reduced Mg and P concentrations by 22.56% and 18.38%, respectively, compared with the Pb-exposed group. Administration of Sal and DFP ameliorated brain injury in Pb-exposed mice and improved histological features. The results suggest the potential application of Sal and DFP for treatment of Pb-induced neurotoxicity.

Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO3)2) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone.

In this study, we present experimental data on the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and tetraethylammonium salt of salinomycinic acid (Sal) on cadmium-induced spleen dysfunction and altered essential metal balance in mice. Sixty-day-old male mice (ICR line) were randomly divided into four groups: untreated control group (Ctrl)-obtained distilled water for 28 days, toxic control group (Cd)-exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg body weight (BW) for 14 days, Cd + DMSA group-obtained cadmium acetate dihydrate as the toxic control group followed by treatment with 20mg/kg BW DMSA for 2 weeks, and Cd + Sal group-mice exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg BW for 2 weeks followed by administration of Sal at an average daily dose of 20mg/kg BW for 2 weeks. The compounds were administered orally via the drinking water of the animals. We found that cadmium exposure caused splenomegaly and reduced the hemoglobin and hematocrit levels and total red blood cell count compared with untreated controls. Cadmium intoxication of mice induced accumulation of the toxic metal ion in the blood and spleen. Alterations in the endogenous levels of calcium (Ca) and iron (Fe) in the spleen of cadmium-exposed mice compared with those in untreated controls were observed. Treatment of cadmium-exposed mice with DMSA or Sal recovered the spleen weight and hematological parameters to normal control values, decreased cadmium concentration in the blood and spleen, and improved splenic architecture. The results prove that Sal is a potential antidote for treatment of Cd-induced spleen dysfunction.

Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all chemotherapy drugs currently on the market cause serious side effects. Fortunately, several studies have shown that some non‐toxic biological macromolecules, including algal polysaccharides, possess anti‐cancer activities or can increase the efficacy of conventional chemotherapy drugs. Polysaccharides are characteristic secondary metabolites of many algae. The efficacy of polysaccharides on the normal and cancer cells is not well investigated, but our investigations proved a cell specific effect of a newly isolated extracellular polysaccharide from the red microalga Porphyridium sordidum. The investigated substance was composed of xylose:glucose and galactose:manose:rhamnose in a molar ratio of 1:0.52:0.44:0.31. Reversible electroporation has been exploited to increase the transport through the plasma membrane into the tested breast cancer tumor cells MCF‐7 and MDA‐MB231. Application of 75 µg/mL polysaccharide in combination with 200 V/cm electroporation induced 40% decrease in viability of MDA‐MB231 cells and changes in cell morphology while control cells (MCF10A) remained with normal morphology and kept vitality.

In this manuscript we discuss different aspects and applications of algal biotechnology and how they are seen through the prism of bioethics. We review how algae have been considered to solve problems on Earth and to ease human suffering. We also take a look at the current state of the production of algal biomass and we offer our suggestions and considerations based on the fact that the biomass is an expensive product and yet its quality is very good.

Cadmium (Cd) is а hazardous multi-organ toxin. In this study, we provide the first results about the effect of oral administration of deferiprone (DFP) on Cd accumulation and on the homeostasis of essential elements in the brain of Cd-exposed mice.Adult Institute of Cancer Research (ICR) male mice were randomized into four experimental groups: untreated controls - administered distilled water for 28 days; Cd-exposed group - exposed to 18 mg/kg body weight (b.w.) Cd(II) acetate for 14 days followed by the administration of distilled water for two weeks; Cd + DFP (low dose) - Cd-intoxicated mice subsequently treated with 19 mg/kg b.w. DFP for two weeks; and Cd + DFP (high dose) - Cd-exposed mice administered high-dose DFP (135 mg/kg b.w.) for 14 days. Brains were subjected to inductively coupled plasma-mass spectrometry (ICP-MS) and histological analysis.The results revealed that exposure of mice to Cd for 14 days significantly increased Cd concentration and significantly decreased magnesium (Mg), phosphorus (P), and zinc (Zn) contents in the brain compared to untreated controls. This effect was accompanied by necrotic-degenerative changes in both the cerebrum and cerebellum. Oral administration of low-dose DFP to Cd-exposed mice decreased the concentration of the toxic metal in the brain by 16.37% and restored the concentration of the essential elements to normal control values. Histological analysis revealed substantially improved cerebral and cerebellar histoarchitectures. In contrast, oral administration of high-dose DFP increased Cd content and significantly decreased selenium (Se) concentration in the brain. Necrotic neurons and Purkinje cells were still observed in the cerebral and cerebellar cortices.The results demonstrated that oral administration of DFP at low doses has a better therapeutic potential for the treatment of Cd-induced brain damage compared to high doses.

In this study, we compare the effects of deferiprone (Def) and tetraethylammonium salt of salinomycinic acid (Sal) on lead (Pb)-induced toxicity in testes of Pb-exposed mice. Mature male ICR mice were allocated into four groups as follows: untreated control mice (ctrl)-received distilled water for 4 weeks; Pb-exposed mice (Pb)-subjected to 14-day Pb (II) nitrate administration at dose 80 mg/kg body weight (b.w.); Pb + Def group-Pb-exposed mice, treated with 20 mg/kg b.w. Def for 2 weeks; and Pb + Sal group-Pb-intoxicated mice, treated with 16 mg/kg b.w. Sal for 14 days. The results demonstrated that Pb exposure significantly increased blood and testicular Pb concentrations, decreased testicular calcium (Ca) content, significantly elevated testicular levels of magnesium (Mg), zinc (Zn), and selenium (Se) but did not significantly affect the endogenous contents of phosphorous (P) and iron (Fe) compared with untreated controls. Pb intoxication induced disorganization of the seminiferous epithelium. Def or Sal administration reduced blood Pb and testicular Pb concentrations in Pb-exposed mice compared with the Pb-intoxicated group. Mg, Zn, and Se concentrations in testes of Pb-exposed mice, treated with Def or Sal, remained higher compared with the untreated controls. Sal significantly increased testicular P concentration compared with untreated controls and significantly elevated the testicular Ca and Fe concentrations compared with the toxic control group. Both chelating agents improved testicular morphology to a great extent. The results demonstrate the potential of both compounds as antidotes for treatment of Pb-induced impairment of male reproductive function.

Cadmium (Cd) is an environmental pollutant shown to induce multi organ dysfunction. In this study we present novel data about the effects of meso-2,3-dimercaptosuccinic acid (DMSA), monensin and salinomycin on the concentration of Cd in skeletal muscles of mice exposed to Cd (II) acetate treatment for 14 days. The impact of Cd and the chelating agents on the endogenous concentrations of calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorous (P), selenium (Se) and zinc (Zn) was also investigated. Subacute exposure of mice to Cd (II) acetate resulted in a significant accumulation of the toxic metal ion in the skeletal muscles compared to the untreated controls. Salinomycin most effectively mobilized Cd from the muscles compared to DMSA and monensin. The Cd exposure and the tested chelating agents did not significantly alter the endogenous concentrations of the selected essential elements in mouse muscles. The presented results confirmed that among the tested chelating agents salinomycin is superior as a potential antidote to Cd poisoning.

Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.

Cadmium (Cd) is a risk factor for neurodegenerative diseases. The purpose of this study was to compare the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and the polyether ionophorous antibiotics monensin and salinomycin on Cd-induced neurodegenerative alterations in mice. The results show that subacute intoxication of mice with Cd (II) acetate (20 mg/kg body weight (BW) for 14 days) caused a significant accumulation of cadmium (Cd) in the brain. Treatment of Cd-exposed mice with DMSA (20 mg/kg BW for 14 days) significantly increased the Cd concentration in the brains compared to those of the Cd-treated group. However, administration of monensin (20 mg/kg BW for 14 days) or salinomycin (20 mg/kg BW for 14 days) significantly reduced the Cd concentration in the brains of Cd-treated mice compared to the toxic control group. Histopathological analysis of brain tissues from the Cd-treated mice revealed that Cd induced neuronal necrosis, characterized by many shrunken, darkly stained pyknotic neurons with prominent perineuronal spaces. Whereas monensin and salinomycin significantly reduced the adverse effects of Cd on brain morphology of Cd-treated mice, DMSA did not. Monensin slightly increased the copper and iron endogenous levels in the brains of Cd-exposed mice compared to those of the untreated mice. Salinomycin did not affect the concentrations of biometal ions in the brain of Cd-exposed mice compared to untreated controls. The results demonstrated salinomycin to be a better potential chelating agent for treatment of Cd-induced brain injury compared to DMSA and monensin.

Isolation and characterization of new biologically active substances affecting cancer cells is an important issue of fundamental research in biomedicine. Trehalose lipid was isolated from Rhodococcus wratislaviensis strain and purified by liquid chromatography. The effect of trehalose lipid on cell viability and migration, together with colony forming assays, were performed on two breast cancer (MCF7&mdash, low metastatic, MDA-MB231&mdash, high metastatic) and one &ldquo, normal&rdquo, (MCF10A) cell lines. Molecular modeling that details the structure of the neutral and anionic form (more stable at physiological pH) of the tetraester was carried out. The tentative sizes of the hydrophilic (7.5 &Aring, ) and hydrophobic (12.5 &Aring, ) portions of the molecule were also determined. Thus, the used trehalose lipid is supposed to interact as a single molecule. The changes in morphology, adhesion, viability, migration, and the possibility of forming colonies in cancer cell lines induced after treatment with trehalose lipid were found to be dose and time dependent. Based on the theoretical calculations, a possible mechanism of action and membrane asymmetry between outer and inner monolayers of the bilayer resulting in endosome formation were suggested. Initial data suggest a mechanism of antitumor activity of the purified trehalose lipid and its potential for biomedical application.

Background and aim Sodium nitrite (NaNO2) is an inorganic salt with numerous applications in a variety of industries, as well as in medicine. Nevertheless, exposure to high levels of NaNO2 is toxic for animals and humans. Sodium nitrite intoxication is shown to decrease the activity of major antioxidant defence enzymes which is dependent on the maintenance of specific ion equilibrium. The aim of the present study was to investigate the effect of acute NaNO2 intoxication on the content of the essential metals iron (Fe), calcium (Ca) and zinc (Zn) in mouse spleen. Methods Mature male ICR mice were divided into four groups and subjected to acute NaNO2 exposure by a single intraperitoneal injection of 120 mg/kg body weight. Animals in each group were sacrificed at certain time interval after treatment (1 h, 5 h, 1 day and 2 days). Spleens were excised and processed for atomic absorption spectrometry analysis of Fe, Ca and Zn content. Results At the first hour after treatment, a decrease in Fe and Ca levels was observed. One day following NaNO2 administration, Zn concentration reached its lowest value and Ca levels remained lower, compared to the untreated controls. In contrast, Fe concentration increased on the first and second day after treatment. Conclusion The results of the present study demonstrate that acute NaNO2 intoxication provokes changes in the endogenous levels of Fe, Ca and Zn in mouse spleen. These findings suggest disruption of the ionic balance and impact on the activity of antioxidant defence enzymes.

Background and aim Environmental lead (Pb) exposure damages the lungs and is a risk factor for death from cardiovascular disease. Pb induces toxicity by a mechanism, which involves alteration of the essential elements homeostasis. In this study we compare the effects of salinomycin (Sal), monensin (Mon) and meso-2,3-dimercaptosuccinic acid (DMSA) on the concentrations of lead (Pb), calcium (Ca), copper (Cu), iron (Fe) and zinc (Zn) in the lungs and heart of lead-exposed mice. Methods Sixty days old male ICR mice were divided into five groups: control (Ctrl) – untreated mice obtained distilled water for 28 days; Pb-intoxicated group (Pb) – exposed to 80 mg/kg body weight (BW) Pb(NO3)2 during the first 14 days of the experimental protocol; DMSA-treated (Pb + DMSA) – Pb-exposed mice, subjected to treatment with an average daily dose of 20 mg/kg BW DMSA for two weeks; Monensin-treated (Pb + Mon) – Pb-exposed mice, obtained an average daily dose of 20 mg/kg BW tetraethylammonium salt of monensic acid for 14 days; Pb + Sal - Pb-exposed mice, treated with an average daily dose of 20 mg/kg BW tetraethylammonium salt of salinomycinic acid for two weeks. On the 29th day of the experiment the samples (lungs and heart) were taken for atomic absorption analysis. Results The results revealed that exposure of mice to Pb for 14 days significantly increased the concentration of the toxic metal in both organs and elevated the cardiac concentrations of Ca, Cu and Fe compared to untreated mice. Pb exposure diminished the lung concentrations of Ca and Zn compared to that of untreated controls. DMSA, monensin and salinomycin decreased the concentration of Pb in the lungs and heart. Among the tested chelating agents, only salinomycin restored the cardiac Fe concentration to normal control values. Conclusion The results demonstrated the potential application of polyether ionophorous antibiotic salinomycin as antidote for treatment of Pb-induced toxicity in the lungs and heart. The possible complexation of the polyether ionophorous antibiotics with Ca(II) and Zn(II), which can diminish the endogenous concentrations of both ions in the lungs should be taken into account.

Determination of biomass production and viability of algal cells of Chlorella vulgaris and Synechocystis salina exposed to UV-B radiation were carried out in this study together with comparison of the mesophilic and antarctic isolates of both investigated strains. Estimation of the content of the pigments: chlorophyll a, chlorophyll b, β-carotene, C-phycocyanin and allo-phycocyanin in algal cells exposed to UV-B radiation was also accomplished. The obtained results showed that the antarctic algae are more resistant to oxidative stress than their mesophilic counterparts. The antarctic isolates of Ch. vulgaris and S. salina compared with the mesophilic ones - up to 72 h showed tolerance to low exposures of radiation, expressed in a slight stimulation of growth and viability of the cells. Antarctic isolates also showed greater resistance to low doses of UV-B radiation manifested by stimulation of the synthesis of chlorophyll a and β-carotene. The registered increase in the amount of C- and allo-phycocyanin in antarctic isolates of S. salina showed that they had developed protective strategies against UV-B radiation by increasing the concentration of the phycobiliproteins. As a result of increased UV-B background, in antarctic isolates, stronger antioxidant defence mechanisms are triggered, which proved the possibility of using them as markers of oxidative stress.

This study presents experimental data on the effects of the tetraethylammonium salt of salinomycinic acid (Sal) on Cd-induced hepatotoxicity and renal dysfunction in Cd-treated mice compared to those of meso-2,3-dimercaptosuccinic acid (DMSA). Forty 60-day-old male ICR mice were randomized into five groups: control group (untreated mice), Cd group (Cd(II) acetate 20 mg/kg body weight provided orally once per day for 14 days), Cd + DMSA group (exposed to Cd(II) acetate as the Cd-exposed group followed by DMSA 20 mg/kg body weight provided orally once per day for 14 days), and Cd + Sal group (exposed to Cd(II) acetate as the Cd-exposed group followed by Sal 20 mg/kg body weight once per day for 14 days). Cd intoxication of mice induced significant liver and kidney injury and a significant elevation of the concentration of Cd in both organs. Treatment of Cd-exposed mice with DMSA or Sal restored the levels of the renal and hepatic functional markers and significantly decreased the concentration of the toxic metal ion in both organs. Administration of Sal improved Cd-induced alterations of the endogenous levels of the essential metal ions. Histological studies revealed that the antibiotic more effectively ameliorated the Cd effect on the liver morphology compared to DMSA. Taken together, the results confirm that the anticancer agent salinomycin is a promising antidote to Cd poisoning.

An in vivo experimental model for testing the effects of long-term chronic treatment with cobalt(II) compounds — cobalt chloride (CoCl2) and cobalt-EDTA (Co-EDTA) on mice at different stages of development was optimized. Pregnant mice and their progeny were treated with daily doses of 75 or 125 mg kg−1 body weight until postnatal day 90. The compounds were dissolved in regular tap water. Mice were sacrificed on days 18, 25, 30, 45, 60 and 90 after birth, which correspond to different stages of their development. Altered organ weight indices (calculated as a ratio of organ weight to body weight) of spleen, liver and kidneys, were found depending on the type of compound used, dose, duration of treatment, and the age of the animals. The results also showed significant accumulation of cobalt ions in blood plasma, spleen, liver and kidneys of the exposed mice. More Co(II) was measured in the organs of the immature mice (day 18, 25 and 30 pnd) indicating that they were more sensitive to treatment.

Cadmium (Cd) is a well-known nephrotoxic agent. Cd-induced renal dysfunction has been considered as one of the causes leading to the development of hypertension. The correlation between Cd concentration in blood and urine and cardiovascular diseases has been discussed in many epidemiological studies. A therapy with chelating agents is utilized for the treatment of toxic metal intoxication. Herein we present novel information indicating that monensin (applied as tetraethylammonium salt) is a promising chelating agent for the treatment of Cd-induced renal and cardiac dysfunction. The study was performed using the ICR mouse model. Adult ICR male mice were divided into three groups with six animals in each group: control (received distilled water and food ad libitum for 28 days); Cd-intoxicated (treated orally with 20 mg/kg b.w. Cd(II) acetate from day 1 to day 14 of the experimental protocol), and monensin treated group (intoxicated with Cd(II) acetate as described for the Cd-intoxicated group followed by oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for 2 weeks). Cd intoxication of the animals resulted in an increase of the organ weight/body weight indexes. Cd elevated significantly creatinine and glucose level in serum. Monensin treatment improved the organ weight/body weight ratios. The therapy of the Cd-intoxicated animals with monensin ameliorated the creatinine and glucose level in serum and decreased the concentration of the toxic metal ions in the heart and kidneys by 54 % and 64 %, respectively

This study was designed to evaluate the potential application of monensin as an oral drug for the treatment of cadmium-induced hepatic dysfunction. The study was performed using ICR mouse model. Twenty-seven adult ICR male mice were divided into three groups of nine animals each: control (received distilled water and food ad libitum for 28 days); Cd-intoxicated (treated orally with 20 mg/kg b.w. Cd(II) acetate from the 1st to the 14th day of the experimental protocol); and monensin treated group (intoxicated with Cd(II) acetate as described for the Cd-intoxicated group followed by an oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for two weeks). The obtained results demonstrated that the treatment of Cd-intoxicated animals with monensin restored the liver weight/body weight index to normal values, decreased the concentration of the toxic metal ion by 50% compared to the Cd-treated controls, and recovered the homeostasis of Cu and Zn. Monensin reduced the activity of aspartate aminotransferase, alanine aminotrasnferase and alkaline phosphatase in the plasma of Cd-treated animals to the normal control levels and ameliorated the Cd-induced inflammation in the liver. Taken together, these data demonstrated that monensin could be an effective chelating agent for the treatment of Cd-induced hepatotoxicity.

Cadmium (Cd) has been classified as a human carcinogen. The World Health Organization (WHO) reported that the concentration of Cd in the environment has rapidly increased in the last few years. In many epidemiological studies, the correlation between environmental exposure of humans to Cd and diseases such as stroke, ischemia, renal and hepatic dysfunction, anemia, osteoporosis and diabetes has been discussed. For the treatment of heavy metal intoxications a therapy with chelating agents has been applied. A chelating agent is a compound that binds the toxic metal ion thus promoting its excretion by the living organisms. Recently, it has been found that Cd-induced toxicity is a result of formation of reactive oxygen species (ROS). These results increased the interest towards the antioxidants as possible agents for the treatment of Cd-induced organ toxicity. Herein, we present summary and discussion of the literature data for the influence of chelating agents and antioxidants on Cd-induced pathological conditions in Cd-intoxicated animals.

In this study, the ability of the chelating agent monensic acid (administered as the tetraethylammonium salt) to reduce the cadmium (Cd) concentration in the kidneys, liver, heart, lungs, spleen and testes of Cd-intoxicated mice was investigated. Chelation therapy with the tetraethylammonium salt of monensic acid led to a significant decrease of the Cd concentration in all of the organs of the Cd-treated mice. This effect varied from 50% in the kidneys to 90% in the hearts of the sacrificed animals (compared to the Cd-treated controls). No redistribution of the toxic metal ions to the brain of the animals as a result of the detoxification with the chelating agent was observed. The detoxification of the animals with the antibiotic salt did not perturb the endogenous levels of copper (Cu) or zinc (Zn). The tetraethylammonium salt of monensic acid significantly ameliorated the Cd-induced total iron (Fe) depletion in the liver and spleen of Cd-treated mice. It also restored to control levels the values of transferrin-bound Fe and the total iron binding capacity (TIBC) of the plasma. These results imply that the tetraethylammonium salt of monensic acid could be an efficient antidote in cases of Cd-intoxication.

The single crystal X-ray structures and the spectroscopic properties of complexes of monensic acid (C36H62O11·H2O) with toxic metal ions of Cd(II) and Hg(II) are discussed. The cadmium(II) complex (1) is of composition [Cd(C36H61O11)2(H2O)2] and crystallizes in the monoclinic system (space group P2(1), Z = 2) with a = 12.4090(8), b = 24.7688(16), c = 14.4358(11) Å, β = 91.979(7)°. Two ligand monoanions are bound in a bidentate coordination mode to Cd(II) via the carboxylate and the primary hydroxyl oxygens occupying the equatorial plane of the complex. The axial positions of the inner coordination sphere of Cd(II) are filled by two water molecules additionally engaged in intramolecular hydrogen bonds. The Hg(II) complex (2), [Hg(C36H60O11)(H2O)], crystallizes in the orthorhombic system (space group P2(1)2(1)2(1), Z = 4) with a = 12.7316(2), b = 16.4379(3), c = 18.7184(4) Å. The monensic acid reacts with Hg(II) in a tetradentate coordination manner via both oxygen atoms of the carboxylate function and oxygens of two hydroxyl groups. The twofold negative charge of the ligand is achieved by deprotonation of carboxylic and secondary hydroxyl groups located at the opposite ends of the molecule. Hg(II) is surrounded by five oxygen atoms in a distorted square pyramidal molecular geometry.

Mononuclear transition metal complexes of the polyether ionophorous antibiotic monensin (monensic acid, MonH) with nickel(II) and zinc(II) were prepared and characterized using single crystal X-ray diffraction and spectral methods. Monensin complexes crystallize as [Ni(Mon) 2 (H 2 O) 2 ]·H 2 O·5MeCN ( 1 ) and [Zn(Mon) 2 (H 2 O) 2 ]·H 2 O·4.5MeCN ( 2 ), respectively, in the monoclinic space group P 2 1 . Compounds 1 and 2 consist of two monoanionic monensic acid ligands (monensinates) bound in a bidentate coordination mode to the transition metal ion. The metal center is placed in an octahedral environment with monensin anions occupying the equatorial plane of complexes via oxygens of carboxylate and hydroxyl groups located at the both ends of ionophore molecule. The strongly folded antibiotic anions are supported by intramolecular H-bonds, most of them originating from the two aqua ligands attached to the metal(II) ions in axial positions and completing their 6-fold coordination. The bioactivity assay reveals that the presence of divalent metal ion in the monensin complexes influences the biological properties of the ligand and should be taken into account when discussing its mode of action.

Heavy metals such as cobalt are shown to accumulate in various organs of humans and animals. Oral exposure of immature mice to cobalt compounds (cobalt chloride and cobalt-EDTA) led to significant ...

In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys>spleen>liver>brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs.

The nitrosation of cellular thiols has attracted much interest as a regulatory mechanism that mediates some of the pathophysiological effects of nitric oxide (NO). In cells, virtually all enzymes contain cysteine residues that can be subjected to S-nitrosation, whereby this process often acts as an activity switch. Nitrosation of biological thiols is believed to be mediated by N2O3, metal-nitrosyl complexes, and peroxynitrite. To date, however, enzymatic pathways for S-denitrosation of proteins have not been identified. Herein, we present experimental evidence that two ubiquitous cellular dithiols, thioredoxin and dihydrolipoic acid, catalyze the denitrosation of S-nitrosoglutathione, S-nitrosocaspase 3, S-nitrosoalbumin, and S-nitrosometallothionenin to their reduced state with concomitant generation of nitroxyl (HNO), the one-electron reduction product of NO. In these reactions, formation of NO and HNO was assessed by ESR spectrometry, potentiometric measurements, and quantification of hydroxylamine and sodium nitrite as end reaction products. Nitrosation and denitrosation of caspase 3 was correlated with its proteolytic activity. We also report that thioredoxin-deficient HeLa cells with mutated thioredoxin reductase denitrosate S-nitrosothiols less efficiently. We conclude that both thioredoxin and dihydrolipoic acid may be involved in the regulation of cellular S-nitrosothiols.

Despite its negative redox potential, nitroxyl (HNO) can trigger reactions of oxidation. Mechanistically, these reactions were suggested to occur with the intermediate formation of either hydroxyl radical (·OH) or peroxynitrite (ONOO–). In this work, we present further experimental evidence that HNO can generate ·OH. Sodium trioxodinitrate (Na2N2O3), a commonly used donor of HNO, oxidized phenol and Me2SO to benzene diols and ·CH3, respectively. The oxidation of Me2SO was O2-independent, suggesting that this process reflected neither the intermediate formation of ONOO– nor a redox cycling of transition metal ions that could initiate Fenton-like reactions. In solutions of phenol, Na2N2O3 yielded benzene-1,2-diol and benzene-1,4-diol at a ratio of 2:1, which is consistent with the generation of free ·OH. Ethanol and Me2SO, which are efficient scavengers of ·OH, impeded the hydroxylation of phenol. A mechanism for the hydrolysis of Na2N2O3 is proposed that includes dimerization of HNO to cis-hyponitrous acid (HO-N=N-OH) with a concomitant azo-type homolytic fission of the latter to N2 and ·OH. The HNO-dependent production of ·OH was with 1 order of magnitude higher at pH 6.0 than at pH 7.4. Hence, we hypothesized that HNO can exert selective toxicity to cells subjected to acidosis. In support of this thesis, Na2N2O3 was markedly more toxic to human fibroblasts and SK-N-SH neuroblastoma cells at pH 6.2 than at pH 7.4. Scavengers of ·OH impeded the cytotoxicity of Na2N2O3. These results suggest that the formation of HNO may be viewed as a toxicological event in tissues subjected to acidosis.

Cobalt (Co) and its compounds are shown to improve hematological parameters. Long-term treatment with Co(II) increased hemoglobin content in a dose- and time-dependent manner in mature mice (day 45 to day 90) while it was reduced in immature mice (day 18 to day 30). Higher Hb was measured in samples treated with CoCl2 compared to those treated with Co-EDTA. Plasma Fe concentration was significantly higher in samples treated with Co-EDTA compared to those exposed to CoCl2. Lower concentrations were measured only in mature animals. Co(II) concentration increased but not in a dose-dependent manner. In general more Co(II) was measured in samples treated with CoCl2 possibly due to the stability of the complex Co-EDTA. Surprisingly, mature mice had less Co(II) in their plasma compared to day 18 mice. Strong correlation between plasma Co(II) and iron concentration was found in samples of mice treated with Co-EDTA. Co(II) concentration showed inverse correlation with hemoglobin in mice treated with low do...

Aims: To evaluate the lytic activities of crude enzymes from Cytophaga sp. LR2 on Rhodella reticulata cells and isolated algal polysaccharide. Methods and Results: The Cytophaga compartment was separated after centrifugation in a cell suspension for 30 min at 18 000 g. The extracellular enzyme was obtained from the supernatant and the intracellular from the pelleted cells after sonication and removal of debris. Algal cells were incubated with extra- or intracellular preparations and sowed onto agar medium. The suppressive effect of the extracellular enzyme on colony-forming units was found to be almost twice as high. The result was still more pronounced when treated cells had been shocked osmotically before seeding. Saccharolytic activity was evaluated by changes in the reducing sugars in the media. Concerning isolated algal polysaccharide, the reducing power of the two bacterial preparates was relatively low. A combined fraction showed the highest lytic activity. Using native and SDS electrophoresis some relation between the prevalence of the extra and intracellular protein patterns was registered. Two of the common components' molecular weight masses of 50 and 21 kDa were found to be reproducible in native- and SDS-containing gel. Conclusions:Cytophaga sp. LR2 produce extra- and intracellular enzymes active in destroying Rhodella cultures. The agents excreted in the medium are more effective.We suppose that two or three different classes of enzymes are involved in the lysis process. The comparative electrophoresis in this case shows the protein components with predictable functions. Significance and Impact of the Study: Combining different simple and reproducible approaches to identify the lytic capability of Cytophaga sp. LR2 on R. reticulata.

The influence of different factors on the lysis of the red microalga, Rhodella reticulata, by Cytophaga sp. LR2 was studied. The pathogenic bacterial strain was more resistant than the alga to the physiological parameters studied, which assured long-term survival of bacteria in algal cultures. Cytophaga sp. LR2 infected R. reticulata at temperatures between 15 and 30 degrees C, in the illuminated as well as the non-illuminated cultures, at pH values between 5.0 and 9.0, and in the presence of NaCl and CaCl2 in the culture medium. SEM showed a different morphology of the bacteria in algal cultures from those of axenic cultures of Cytophaga. Observations of specific associations between algal and bacterial cells revealed that the role of the slime extrusions on the bacterial surface was attachment of Cytophaga to algal cells, and that their clumping leads to rapid lysis.

A bacterium was isolated which caused disease in a laboratory culture of the red alga, Rhodella reticulata. The organism was an aerobic Gram-negative rod, aflagellate and pigmented. The absorption maximum of the pigments in methanol was 460 nm. The bacterium showed hydrolytic activity towards agar and produced extracellular agarase. The organism utilized monosaccharide constituents of the polysaccharide of R. reticulata, as well as the whole polysaccharide of alga, as a sole carbon source. The bacterium was identified as Cytophaga sp. LR 2 .

The present paper describes the isolation, physiological and genetic characteristic of a bacterial agent which inhibits the growth of algae and causes death of laboratory cultures of Antarctic microalgal strains: prokaryotic cyanobacteria Synechocystis salina and green eukaryotic microalga Choricistis minor. The bacterial strain LB1 was isolated from algal damaged laboratory cultures of S. salina. It was established that this bacterium is obligate aerobic, Gram-positive, non-spore-forming, immotile, irregular rods with dimensions 0.3–2 μm. Our results showed that LB1 has algicidal effect to S. salina as well as to C. minor. Transmission electron microscopy observations confirmed the destruction of S. salina by the bacterium. Biochemical analysis of LB1 revealed positive reaction to d-glucose, catalase, hydrolysis of gelatin, acid production from: lactose, l-arabinose, l-ramnose, esculin and β-galactosidase. The partial sequence (1,404 bp) of the 16S rRNA gene of LB1 showed 99 % similarity with type strains of the genus Microbacterium. The results of the biochemical, antimicrobial and of 16S rRNA analysis of LB1 allowed us to identify LB1 as Microbacterium sp. Studying expression of pathogenicity of the bacteria to algal cultures will help to solve the problem of algal production for biotechnological purposes.

This study investigated the effects of cadmium (Cd) and monensin on spleen function in mice, subjected to subacute Cd-intoxication. Adult male ICR mice were divided into three groups (n = 6 per group) as follows: control group (received distilled water and food ad libitum); Cd-treated (20 mg/kg/b.w./day Cd(II) acetate for the first 2 weeks of the experimental protocol); monensin-treated mice (20 mg/kg/day Cd(II) acetate for the first 2 weeks followed by treatment with 16 mg/kg b.w./day monensin from days 15 to 28. On day 29, mice were sacrificed under light ether anesthesia. Exposure to Cd induced an increase in spleen index (SI). The treatment of cd-intoxicated mice with monensin significantly reduced SI compared to Cd alone. The data from the atomic absorbption analysis of spleen revealed a significant Cd accumulation in Cd-treated mice compared to controls, accompanied by a significant depletion of Fe concentration up to 30%. The treatment of the Cd-administered mice with monensin resulted in a significant decrease of Cd in spleen by 50% compared to Cd alone. Fe recovery occured in spleen of monensin-treated mice. Histopathological analysis of spleen showed that Cd significantly decreased the number of megakaryocytes and disturbed extramedullary hematopoiesis. The number of megakaryocytes increased when monensin was added. The data in this study suggest that monensin was able to reduce the effects of Cd on hematopoesis in mice.

Despite its negative redox potential, nitroxyl (HNO) can trigger reactions of oxidation. Mechanistically, these reactions were suggested to occur with the intermediate formation of either hydroxyl radical (.OH) or peroxynitrite (ONOO-). In this work, we present further experimental evidence that HNO can generate.OH. Sodium trioxodinitrate (Na2N2O3), a commonly used donor of HNO, oxidized phenol and Me2SO to benzene diols and.CH3, respectively. The oxidation of Me2SO was O2-independent, suggesting that this process reflected neither the intermediate formation of ONOO- nor a redox cycling of transition metal ions that could initiate Fenton-like reactions. In solutions of phenol, Na2N2O3 yielded benzene-1,2-diol and benzene-1,4-diol at a ratio of 2:1, which is consistent with the generation of free.OH. Ethanol and Me2SO, which are efficient scavengers of.OH, impeded the hydroxylation of phenol. A mechanism for the hydrolysis of Na2N2O3 is proposed that includes dimerization of HNO to cis-hyponitrous acid (HO-N=N-OH) with a concomitant azo-type homolytic fission of the latter to N2 and.OH. The HNO-dependent production of.OH was with 1 order of magnitude higher at pH 6.0 than at pH 7.4. Hence, we hypothesized that HNO can exert selective toxicity to cells subjected to acidosis. In support of this thesis, Na2N2O3 was markedly more toxic to human fibroblasts and SK-N-SH neuroblastoma cells at pH 6.2 than at pH 7.4. Scavengers of.OH impeded the cytotoxicity of Na2N2O3. These results suggest that the formation of HNO may be viewed as a toxicological event in tissues subjected to acidosis.

The concentrations of lanthanoids, Be, Bi,Ga, Te, Tl, Th and U have been determined using ICP-MS for 100 standardized samples of poplar leaves collected from the territory of Bulgaria. The investigated elements are log-normally distributed on the territory. Using cluster analysis of the analytical data the samples were grouped according soil type on which the plants are growing.

Background The natural polyether ionophorous antibiotics are used for the treatment of coccidiosis in poultry and ruminants. They are effective agents against infections caused by Gram-positive microorganisms. On the other hand, it was found that some of these compounds selectively bind lead(II) ions in in vivo experiments, despite so far no Pb(II)-containing compounds of defined composition have been isolated and characterized. To assess the potential of polyether ionophores as possible antidotes in the agriculture, a detailed study on their in vitro complexation with toxic metal ions is required. In the present paper we report for the first time the preparation and the structure elucidation of salinomycin complexes with ions of cadmium(II) and lead(II). Results New metal(II) complexes of the polyether ionophorous antibiotic salinomycin with Cd(II) and Pb(II) ions were prepared and structurally characterized by IR, FAB-MS and NMR techniques. The spectroscopic information and elemental analysis data reveal that sodium salinomycin (SalNa) undergoes a reaction with heavy metal(II) ions to form [Cd(Sal)2(H2O)2] (1) and [Pb(Sal)(NO3)] (2), respectively. Abstraction of sodium ions from the cavity of the antibiotic is occurring during the complexation reaction. Salinomycin coordinates with cadmium(II) ions as a bidentate monoanionic ligand through the deprotonated carboxylic moiety and one of the hydroxyl groups to yield 1. Two salinomycin anions occupy the equatorial plane of the Cd(II) center, while two water molecules take the axial positions of the inner coordination sphere of the metal(II) cation. Complex 2 consists of monoanionic salinomycin acting in polydentate coordination mode in a molar ratio of 1: 1 to the metal ion with one nitrate ion for charge compensation. Conclusion The formation of the salinomycin heavy metal(II) complexes indicates a possible antidote activity of the ligand in case of chronic/acute intoxications likely to occur in the stock farming.