Ilona Sadauskiene

Selective induction of IL-6 by aluminum-induced oxidative stress can be prevented by selenium

In this study the acute toxic effects of aluminum (Al) on mice have been investigated, including the interactions of Al and selenium (Se). Focus was put on the systemic effects of (co)exposure to Al and Se as a reflection of the redox status in the liver, kidney and brain. Short-term exposure (16 h) to Al resulted in an increase in the systemic inflammation parameters IL-6 and PAI-1, whereas serum levels of TNF-α remained unaffected. The different response pattern of IL-6 and TNF-α probably indicates an increased intracellular oxidative stress and altered redox status in the liver, because the selective increase in IL-6 serves as a protective intrahepatocellular process driven by oxidative stress. The intracellular glutathione concentration GSHtot decreased significantly upon Al exposure. Both the increase in IL-6 and decrease in glutathione status could be prevented by co-exposure to Se, but not the increase in PAI-1. The redox status of the kidney and brain was not markedly affected. Therefore it was concluded that short-term exposure to Al causes adverse effects on the intracellular oxidative stress processes in the liver, as reflected by the selective increase in the IL-6 concentration. This process can be restored by co-administration of the trace element Se as a part of the glutathione redox system.

Estimation of the combined effect of Eleutherococcus senticosus extract and cadmium on liver cells.

Cadmium (Cd) is an important industrial pollutant, even though its mechanism of toxicity has not been completely clarified. Cd2+ is toxic to a wide range of organs and tissues. Liver and kidneys are the primary target organs of cadmium toxicity. Cd2+ induces apoptosis and causes necrotic cell death in certain pathophysiological situations. Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. has many beneficial features. It supports the organisms stress response, immune system, and endocrine system, including the adrenal glands, spleen, and thymus gland. The aim of our study was to investigate the effects of the Eleutherococcus senticosus (ES) liquid extract on the accumulation of Cd2+ in liver and on the mitotic and apoptotic activity of liver cells after chronic intoxication by Cd2+. Experiments were carried out on white laboratory mice. Laboratory mice were given to drink solutions of different Cd2+ and ES concentrations for 8 weeks. Cd2+ concentration in mouse liver was detected using atomic absorption spectroscopy. Mitotic and apoptotic activity of liver cells was expressed as an estimated number of mitotic and apoptotic cells in randomly selected reference areas in a histological slide. ES combined with CdCl2 leads to a significant decrease of cadmium concentration in the blood and liver of experimental mice. ES decreased the cadmium‐induced mitotic and apoptotic activity of liver cells.

Influence of Echinacea purpurea (L.) Moench extract on the toxicity of cadmium.

Abstract:  Echinacea purpurea (L.) Moench (EP) has many beneficial features, especially strengthening the immune system. Cadmium (Cd) is a ubiquitous metal and cumulative poison that may cause liver and kidney damage and the formation of neoplasia. In this article, the changes in organs and metabolism, the accumulation of various levels of Cd in tissues, and the effects of EP liquid extract on Cd‐induced changes in mice were investigated. Experiments were carried out on the white laboratory mice. Solution of different Cd and EP concentrations were given to drink and experiments were performed. The concentration of Cd in mice blood, liver, kidneys, heart, spleen, skeletal muscle was determined using an electrothermal graphite furnace atomic absorption spectrophotometer Perkin–Elmer/Zeeman 3030. Long time per os of extract of EP combined with Cd leads to a significant increase of Cd concentration in blood and investigated organs of experiment mice.

The effects of cadmium chloride and sodium selenite on protein synthesis in mouse liver.

The study aimed at evaluating the effects of cadmium and selenite ions on protein synthesis and metallothioneins content in mice liver after 2 h, 8 h, 24 h and 14 days of exposure. Our studies revealed that cadmium suppressed protein synthesis after 2 h and 24 h, but activated after 8h and 14 days. Also, the endogenous mRNA translation were reduced under any exposure to cadmium, meanwhile, metallothioneins content was decreased after 2 h, but then was progressively increasing up to 492% after 14 days. Meantime, selenite did not influence metallothioneins content, caused mild activation of protein synthesis, and slightly suppressed the endogenous mRNA translation. The combined treatments with cadmium and selenite favored toward resisting of protein synthesis to cadmium after 2 h and 24 h of intoxication. Besides, selenite also protected translation against cadmium in cell-free systems, but did not attenuate effects of cadmium on metallothioneins content.

Assessment of the Effect of Echinacea purpurea (L.) Moench on Apoptotic and Mitotic Activity of Liver Cells during Intoxication by Cadmium

Abstract:  Cadmium (Cd2+) is an important industrial pollutant, although its mechanism of toxicity has not been completely clarified. Cd2+ is toxic to a wide range of organs and tissues, however, the primary target organs of Cd2+ toxicity are the liver and kidney. Echinacea purpurea stimulating one or another tread of the immune system stimulates the expression of immunoglobulins and interferons. The experiments were performed on white laboratory mice using intraperitoneal (i.p.) injections 0.05 LD50 amount of CdCl2 solution. Two groups of mice were injected by Echinacea purpurea liquid extract: one 0.05 LD50 and the other 0.1 LD50. In this article, the Cd2+ distribution in internal organs, its effect on the mitotic and apoptotic activity of liver cells, as well as effects of Echinacea purpurea liquid extract on Cd2+‐induced changes in mice were investigated. Cd2+ concentration in mice blood, liver, and kidney was detected by atomic absorption spectroscopy. Long‐term injections of extract of Echinacea purpurea combined with Cd2+Cl2 leads to the significant increase of Cd2+ concentration in blood and investigated organs of experimental mice. Mitotic and apoptotic activity of liver cells was expressed as the estimated number of mitotic and apoptotic liver cells in randomly selected reference areas in histological slide. Echinacea purpurea decreases the mitotic activity of liver cells induced by Cd2+ and increases apoptotic activity of the liver cells.

Mice liver protein synthesis in vivo and in vitro after cadmium chloride administration

Objective: To evaluate effects of cadmium ions on the protein synthesis in mice liver in vivo and in vitro. Methods: Experiments were done on white laboratory mice using i.p. injections of appropriate amounts of cadmium chloride solution. Protein synthesis or tRNA acceptor activity was evaluated by the incorporation of [ 14 C]-leucine into newly synthesized peptides and proteins or formation of aminoacyl-tRNA. Liver cell-free translation system was made on the basis of post-mitochondrial supernatant. Results: Single doses of Cd 2+ at the amounts equal to 0.025 LD 50 and 0.05 LD 50 (0.08 mg/kg and 0.16 mg/kg) do not have very significant impact on the protein synthesis in liver 24 h after the heavy metal administration. Only 0.5 LD 50 Cd 2+ (1.6 mg/kg) reduces protein synthesis by approximately one third. However, within 24 h after the intoxication with 0.5 LD 50 , cadmium revealed initial inhibition of translation within the first 2 - 4 h, which progressed into stimulation, reaching its maximum at the 8th h and subsequent decrease. In vitro cadmium at lower concentration (40 μM) demonstrated stimulatory effect on both measured parameters of translation -the rate and level, while sharp inhibition of protein synthesis began only at relatively high concentration of this heavy metal (above 60 pM). When treated in vivo, 0.5 LD 50 cadmium 2 h after injection reduced the acceptor activity of tRNA almost by 50%, but already 8 h after the injection acceptor activity of tRNA was back at the level of control. Cadmium chloride when added directly to the liver extracts of control animals displayed very strong inhibitory effect on the tRNA acceptor activity, which had linear dependence on the cadmium concentration. Conclusions: Cadmium induces significant fluctuations of liver protein synthesis at the early stages of intoxication in vivo, which includes both inhibition and stimulation. Cadmium significantly reduces the acceptor activity of liver tRNA both in vivo and in vitro.

Biomarkers of Selenium Toxicity after Sub-Acute Exposure in Mice

Selenium (Se) is a trace element, essential for human health but it can be toxic at moderately higher intake levels. In this study biomarkers of Se toxicity after sub-acute intra-peritoneal exposure to Se (62.5 µg Se/kg bw/ day; 14 days) were investigated in mice. Such exposure corresponds to high human Se-intake levels. Focus was put on the biomarkers of systemic effects and on the toxicity in liver, kidney and brain. The sub-acute exposure to Se resulted in an increase in the concentrations of systemic inflammation biomarkers IL-6 (p=0.025) and resistin (p=0.049) and in a decrease of TNF-α (p=0.008). No effect on concentrations of MCP-1, tPAI-1, leptin and insulin was observed in serum. Also biomarkers of oxidative stress, anti-oxidant parameters and enzymes ALT and AST were not affected. In the tissue homogenates of liver, kidney and brain changes were observed in the activities of enzymes LDH (p=0.013), ALP (p=0.0009) and GGT (p=0.0047). In the brain homogenate an influx of TG (p=0.0044) and a decrease in the total GSH concentration (p=0.008) was observed. It was concluded that although the sub-acute exposure to a relatively high concentration of Se causes an increase in concentration of some biomarkers of intracellular processes, especially in the brain, the effect of Se can be considered as low toxicity.

The Effects of Buckwheat Leaf and Flower Extracts on Antioxidant Status in Mouse Organs

This study was undertaken to investigate the effects of the extracts of buckwheat leaf and flower on the antioxidant status of the brain and liver tissue. The administration of buckwheat extracts (both concentrations were 10%) to mice (at the dose 10 mL/kg of body weight) for 21 days significantly decreased superoxide dismutase (SOD) activity and reduced the amount of glutathione (GSH) and malondialdehyde (MDA) in the mouse brain, while catalase (CAT) activity significantly increased. In the mouse liver, the amount of GSH and activity of SOD increased, while the CAT activity after administering buckwheat leaf and flower extracts was lower in experimental mice than in the control group. However, the administration of 10% ethanol (for 21 days) to control animals also had a significant effect on the antioxidant system in brain and liver cells. Experimental animals demonstrated rather marked changes in the activities of the antioxidant enzymes SOD and CAT in their liver and brain cells, and changes in the levels of GSH and MDA were observed when compared with the control group.

Effect of Acanthopanax senticosus on the Accumulation of Cadmium and on the Immune Response of Spleen Cells

Exposure to cadmium (Cd) is known to alter immune responses. Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS) extract, an antioxidant-containing complex of phenolic compounds, tetracyclic triterpenoids/steroids, and polysaccharides, is known to produce Cd mobilization and excretion in vivo. Building upon earlier findings, the aim of the study was to evaluate the effects of an AS extract on Cd accumulation and changes in the presence of splenic immune cells in hosts during a chronic metal exposure. Chronic Cd exposure of BALB/c mice was induced by providing them solutions containing different levels of CdCl2 (25 or 250 mg/L) in double-distilled water, with/without a concurrent presence of AS root extract (approximately 151 g material/L), for 8 wk. At the study end, Cd levels in spleen were measured. Levels of key splenic immune cells, including macrophages, T-lymphocytes, and B-lymphocytes, were determined by immunohistochemistry using, respectively, CD68, CD3, and CD20 antibodies. The results indicated that chronic consumption of AS extract in the presence of the high dose of CdCl2 led to a significant decrease in Cd levels in mouse spleen. The effects of AS on the lower CdCl2 dose were less apparent. In addition, the presence of AS and Cd increased the amount of macrophages and both B and T lymphocytes in mouse spleen relative to concentrations that were lowered as a result of chronic metal only intake.

The Relationship of Echinacea purpurea. to the Toxicity of Cadmium

ABSTRACT Cadmium (Cd) is a ubiquitous metal and cumulative poison that may cause liver and kidney damage and the formation of neoplasia. The experiments were performed on white laboratory mice using intraperitoneal injections of 0.05 LD50 of cadmium chloride solution. Two groups of mice were injected with Echinacea purpurea. (L.) Moench liquid extract: one 0.05 LD50 and the other 0.1 LD50. Cd concentration in mouse blood, kidneys, liver, spleen, heart, and skeletal muscles was detected by atomic absorption spectroscopy. Estimated mitotic index of liver cells reflected the mitotic activity in the liver. Mitotic index in liver cells increases under the Cd intoxication, but it remains unchanged after simultaneous injection of Cd and Echinacea purpurea. liquid extract. In this study, the changes in organs and metabolism, the accumulation of various levels of intraperitoneal Cd in tissues, and the effects of Echinacea purpurea. liquid extract on Cd-induced changes in mice were investigated.