OBJECTIVETo assess the cytotoxicity of carbon-coated iron nanoparticles (CCIN) and epirubicin-loaded CCIN on Hep-G2 cells in vitro and compare the acute toxicities of epirubicin and epirubicin-loaded CCIN in mice.

METHODSThe cytotoxicities of CCIN and epirubicin-loaded CCIN on HepG2 cells were assessed using MTT assay, and the uptake of CCIN by the tumor cells was observed by optical and electron microscopy. Different doses of epirubicin and equivalent doses of epirubicin-loaded CCIN were injected intravenously in mice to compare their acute toxicities.

RESULTSOptical and electron microscopy revealed cytoplasmic uptake of CCIN in the tumor cells without obvious destruction of the cell structural integrity. Incubation of the HepG-2 cells with different concentrations of CCIN suspension did not result in significant variation in the mean absorbance. MTT assay showed reduced cytotoxicity of epirubicin-loaded CCIN in HepG2 cells as compared with that of epirubicin alone. The cell growth inhibition rate was significantly higher with epirubicin-CCIN mixture that contained a lower proportion of CCIN. In acute toxicity experiment with mice, the median lethal dose (LD(50)) of epirubicin was 16.9 mg/kg, while that of epirubicin-CCIN mixture was 20.7 mg/kg.

CONCLUSIONCCIN uptake by HepG-2 cells does not cause obvious cytotoxicity in vitro within a certain concentration range, epirubicin-loaded CCIN has reduced cytotoxicity against HepG2 cells as compared with epirubicin, and the cytotoxicity of the mixture decreases with the increase in the CCIN content in the mixture. Epirubicin delivery in mixture with CCIN can reduce its acute toxicity in mice.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; toxicity ; Carbon ; pharmacology ; toxicity ; Drug Carriers ; pharmacology ; toxicity ; Epirubicin ; pharmacology ; toxicity ; Ferric Compounds ; pharmacology ; toxicity ; Hep G2 Cells ; Humans ; Iron ; pharmacology ; toxicity ; Mice ; Nanoparticles ; toxicity ; Toxicity Tests, Acute

In this study, the general toxicity tests including acute toxicity test, haemolysis test, MTT assay of Ti-Fe-Mo-Mn-Nb-Zr alloys were carried out. The morphology of these cells was also observed under phase-contrast microscope. By using X-ray photoelectron spectroscopy(XPS), the kind and mol% of element in surface film were studied. The kind and concentration of element in dipping fluid were investigated by ICP atomic emission spectrometry. The results showed the primary component is TiO2 in surface film. The dipping fluid of Ti-Fe-Mo-Mn-Nb-Zr alloys contains Fe 0.2-1.07 mg/l and Mn 0.16-0.5 mg/l; such dental materials are beneficial to health. No cytotoxic effect was disclosed by in vitro and in vivo tests. The level of cytotoxicity was grade 0 and 1; the haemolysis degree was 0.558%-0.642%, i.e. less than 5%. The cells growing in the extract showed normal morphology. These data indicate that Ti-Fe-Mo-Mn-Nb-Zr alloy, as a dental material, has good biocompatibility.
Animals ; Biocompatible Materials ; chemistry ; toxicity ; Dental Alloys ; toxicity ; Iron ; toxicity ; Male ; Manganese ; Mice ; Molybdenum ; toxicity ; Niobium ; toxicity ; Osmotic Fragility ; Rabbits ; Random Allocation ; Spectrometry, X-Ray Emission ; Titanium ; toxicity ; Zirconium ; toxicity

OBJECTIVEPrevious work has showed that excess iron accumulation is harmful to reproduction and even promotes death; however, whether the multiple biological toxicity of iron (Fe) exposure could be transferred to progeny remains unknown. The present study used Caenorhabditis elegans to analyze the multiple toxicities of iron exposure and their possible transferable properties.

METHODSThree concentrations of iron sulfate solution (2.5 micromol/L, 75 micromol/L, and 200 micromol/L) were used. The endpoints of lifespan, body size, generation time, brood size, head thrash and body bend frequencies, and chemotaxis plasticity were selected to investigate Fe toxicity and its effect on progeny in Caenorhabditis elegans.

RESULTSThe Fe toxicity could cause multiple biological defects in a dose-dependent manner by affecting different endpoints in nematodes. Most of the multiple biological defects and behavior toxicities could be transferred from Fe-exposed Caenorhabditis elegans to their progeny. Compared to the parents, no recovery phenotypes were observed for some of the defects in the progeny, such as body bend frequency and life span. We further summarized the defects caused by Fe exposure into 2 groups according to their transferable properties.

CONCLUSIONOur results suggest that Fe exposure could cause multiple biological defects, and most of these severe defects could be transferred from Fe exposed nematodes to their progeny.

Animals ; Behavior, Animal ; drug effects ; physiology ; Body Size ; Caenorhabditis elegans ; drug effects ; genetics ; physiology ; Dose-Response Relationship, Drug ; Iron ; toxicity ; Iron Compounds ; toxicity ; Life Expectancy ; Phenotype ; Reproduction ; Soil Pollutants ; toxicity ; Sulfates ; toxicity

OBJECTIVETo study the acute toxicity of carbon-coated iron nanocrystal (CCIN) in mice and its effects on hepatic, renal and hematological functions.

METHODSAcute toxicity of CCIN was evaluated by observing the toxic reactions in mice within 14 days following intravenous injection of different doses of CCIN particles. The liver and kidney functions and blood chemistry were tested in rats before and at different time points after CCIN injection.

RESULTSThe median lethal dose (LD(50)) of CCIN particles given by intravenous injection was 203.8 mg /kg in mice. Within the intravenous dose of 80 mg /kg injection, CCIN caused only mild alterations of the rats' biochemical and hematological indices that recovered without intervention in two weeks.

CONCLUSIONCCIN is characterized by low acute toxicity and mild side effects on the hepatic, renal and hematological functions within a certain dose range.

Animals ; Blood Chemical Analysis ; Carbon ; toxicity ; Iron ; administration & dosage ; toxicity ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Male ; Mice ; Mice, Inbred BALB C ; Nanoparticles ; administration & dosage ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo establish a mouse model of iron overload by intraperitoneal injection of iron dextran and investigate the impact of iron overload on bone marrow hematopoiesis.

METHODSA total of 40 C57BL/6 mice were divided into control group, low-dose iron group (12.5 mg/ml), middle-dose iron group (25 mg/ml), and high-dose iron group (50 mg/ml). The control group received normal saline (0.2 ml), and the rest were injected with intraperitoneal iron dextran every three days for six weeks. Iron overload was confirmed by observing the bone marrow, hepatic, and splenic iron deposits and the bone marrow labile iron pool. In addition, peripheral blood and bone marrow mononuclear cells were counted and the hematopoietic function was assessed.

RESULTSIron deposits in bone marrow, liver, and spleen were markedly increased in the mouse models. Bone marrow iron was deposited mostly within the matrix with no significant difference in expression of labile iron pool.Compared with control group, the ability of hematopoietic colony-forming in three interventional groups were decreased significantly (P<0.05). Bone marrow mononuclear cells counts showed no significant difference. The amounts of peripheral blood cells (white blood cells, red blood cells, platelets, and hemoglobin) in different iron groups showed no significant difference among these groups;although the platelets were decreased slightly in low-dose iron group [(780.7±39.60)×10(9)/L], middle dose iron group [(676.2±21.43)×10(9)/L], and high-dose iron group [(587.3±19.67)×10(9)/L] when compared with the control group [(926.0±28.23)×10(9)/L], there was no significant difference(P>0.05).

CONCLUSIONSThe iron-overloaded mouse model was successfully established by intraperitoneal administration of iron dextran. Iron overload can damage the hepatic, splenic, and bone marrow hematopoietic function, although no significant difference was observed in peripheral blood count.

Animals ; Bone Marrow ; drug effects ; physiopathology ; Disease Models, Animal ; Hematopoiesis ; drug effects ; Iron Overload ; chemically induced ; physiopathology ; Iron-Dextran Complex ; administration & dosage ; toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Spleen ; drug effects

OBJECTIVETo investigate the effects of exposure to aluminum (Al) on Zn, Fe, Cu and Ca contents in hippocampus of rats.

METHODSAlCl(3).6H(2)O was administered orally through diet (8% of body weight) to SD rats at doses of 0 (A), 11.2 (B), 55.9 (C), 111.9 (D) mg Al(3+)/kg BW for successive 90 days. Then Al, Zn, Fe, Cu and Ca contents in hippocampi of rats were determined by atomic absorption spectrophotometry.

RESULTSAfter oral exposure to Al, the Al content in hippocampus of rat increased significantly with a remarkable dose-effect relationship (r = 0.731, P < 0.001), The Zn, Fe, Ca and Cu contents in these four groups are as follows: Group A (18.29 +/- 2.48, 24.86 +/- 1.97, 48.69 +/- 22.08, 4.53 +/- 0.99) mg/g, Group B (17.22 +/- 2.06, 27.54 +/- 2.87, 42.79 +/- 14.42, 4.06 +/- 0.41) mg/g, Group C (14.46 +/- 1.90, 20.18 +/- 2.79, 29.95 +/- 7.33, 3.98 +/- 0.25) mg/g, Group D (15.85 +/- 2.54, 20.96 +/- 2.83, 36.14 +/- 12.66, 4.53 +/- 0.58) mg/g. Compared with the control group A, the Zn and Fe contents in group B and group C decreased significantly (P < 0.05), and the Ca content in group C also decreased significantly.

CONCLUSIONOral exposure to Al may result in accumulation of Al in hippocampus of brain and thus affect some essential elements (Zn, Fe, Cu and Ca) contents in the hippocampus at different degrees.

Aluminum ; metabolism ; pharmacology ; toxicity ; Animals ; Calcium ; metabolism ; Copper ; metabolism ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; metabolism ; Iron ; metabolism ; Male ; Metals ; metabolism ; Rats ; Rats, Sprague-Dawley ; Zinc ; metabolism

To investigate the Fe2+ effects on root tips in rice plant, experiments were carried out using border cells in vitro. The border cells were pre-planted in aeroponic culture and detached from root tips. Most border cells have a long elliptical shape. The number and the viability of border cells in situ reached the maxima of 1600 and 97.5%, respectively, at 20-25 mm root length. This mortality was more pronounced at the first 1-12 h exposure to 250 mg/L Fe2+ than at the last 12-36 h. After 36 h, the cell viability exposed to 250 mg/L Fe2+ decreased to nought, whereas it was 46.5% at 0 mg/L Fe2+. Increased Fe2+ dosage stimulated the death of detached border cells from rice cultivars. After 4 h Fe2+ treatment, the cell viabilities were > or =80% at 0 and 50 mg/L Fe2+ treatment and were <62% at 150, 250 and 350 mg/L Fe2+ treatment; The viability of border cells decreased by 10% when the Fe2+ concentration increased by 100 mg/L. After 24 h Fe2+ treatment, the viabilities of border cells at all the Fe2+ levels were <65%; The viability of border cells decreased by 20% when the Fe2+ concentration increased by 100 mg/L. The decreased viabilities of border cells indicated that Fe2+ dosage and treatment time would cause deadly effect on the border cells. The increased cell death could protect the root tips from toxic harm. Therefore, it may protect root from the damage caused by harmful iron toxicity.
Iron ; toxicity ; Oryza ; cytology ; drug effects ; growth & development ; Plant Roots ; cytology ; drug effects ; growth & development ; Seedlings ; cytology ; drug effects ; growth & development

Foundry workers are potentially exposed to a number of carcinogens. This study was conducted to describe the cancer incidence associated with employment in small-sized Korean iron foundries and to compare those findings to the Korean population. Cancer morbidity in 208 Korean foundries was analyzed using the Standardized Incidence Ratio (SIR) and Standardized Rate Ratio (SRR). Overall cancer morbidity in foundry workers (SIR=1.11, 95% confidence interval [CI]=1.01-1.21) was significantly higher than that of Korean general population. Lung cancer (SIR=1.45, 95%CI=1.11-1.87) and lymphohematopoietcic cancer (SIR=1.58, 95%CI=1.00-2.37) in production workers were significantly high compared to Korean general population. Stomach cancer in fettling (SRR=2.10, 95%CI=1.10-4.01) and lung cancer in molding (SRR=3.06, 95%CI=1.22-7.64) and in fettling (SRR=2.63, 95%CI=1.01-6.84) were there significant elevations compared to office workers. In this study, statistically significant excess lung cancer was observed in production workers comparing to Korean general population and office workers. Also, cancer morbidity of overall cancer, lung cancer and stomach cancer was significantly increased with duration of employment at ten and more years comparing to Korean general population. These findings suggest in causal association between exposure to carcinogens during foundry work and cancer morbidity.
Adult ; Aged ; Carcinogens/toxicity ; Cohort Studies ; Female ; Humans ; Iron/toxicity ; Lung Neoplasms/epidemiology/mortality ; Male ; Middle Aged ; Morbidity ; Neoplasms/*epidemiology/mortality ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Republic of Korea ; Stomach Neoplasms/epidemiology/mortality

OBJECTIVE: This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity. METHODS: Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed. RESULTS: CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model. CONCLUSION These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.
Animals ; Blood Chemical Analysis ; Carbon Tetrachloride ; toxicity ; Hepcidins ; pharmacology ; Injections, Intraperitoneal ; Interleukin-6 ; pharmacology ; Iron ; blood ; metabolism ; Leukocytosis ; chemically induced ; therapy ; Liver Cirrhosis ; chemically induced ; therapy ; Male ; Rats ; Thioacetamide ; toxicity ; Thrombocytopenia ; chemically induced ; therapy ; Transferrin ; metabolism

The aim of the present study was to explore the effect of nitric oxide (NO) on iron-induced toxicity in rat hearts. Langendorff perfused rat heart and enzymatically isolated cardiomyocytes were used. It was shown that lipophilic Fe-HQ reduced the contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte, while the left ventricular developed pressure (LVDP), +/-dp/dt(max), heart rate and coronary flow showed biphasic alterations, which increased in the first 2 min and then was followed by a decline in isolated perfused rat heart; the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the malondialdehyde (MDA) in the myocardium were increased. L-arginine (L-Arg), an NO precursor, reduced the contractile amplitude and end-diastolic cell length in the cardiomyocyte; but reversibly increased LVDP, +/-dp/dt(max), and coronary flow in isolated perfused rat heart. Pretreatment with L-Arg aggravated the Fe-HQ-induced decrease in contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte; LVDP, +/-dp/dt(max), heart rate and coronary flow were significantly reduced in the perfused heart, and the levels of LDH and CK increased in the coronary effluent. In contrast, the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) blocked the Fe-HQ induced change in contractile amplitude, velocity and end-diastolic cell length in the cardio- myocyte; it inhibited the decrease in LVDP, LVEDP and +/-dp/dt(max), and reduced the LDH and CK. Removing endothelial cells in coronary vessels attenuated the increase in LVDP and +/-dp/dt(max) at the beginning of Fe-HQ perfusion. It is suggested that L-Arg aggravates the iron-induced cardiac dysfunction, NO can mediate the iron-induced toxicity in heart, and endothelial cells in coronary vessels play an important role in the early stage of the effect of iron.
Animals ; Arginine ; pharmacology ; Coronary Vessels ; cytology ; Creatine Kinase ; metabolism ; Endothelial Cells ; drug effects ; Heart ; drug effects ; Iron ; toxicity ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Myocardium ; metabolism ; Myocytes, Cardiac ; cytology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Rats