Developmental exposure to cobalt chloride affected mouse testis via altered iron metabolism in adulthood.

INRODUCTION: Cobalt (Co) is known to interfere with iron (Fe) metabolism that is essential for differentiating male germ cells. Our aim was to study the effect of developmental chronic cobalt exposure on mouse testis through changes in iron homeostasis in adulthood. METHODS: Pregnant ICR mice were exposed to 75 mg (low dose) or 125 mg (high dose)/kg b.w. cobalt chloride (CoCl2) with drinking water for 3 days before delivery and treatment continued until postnatal day 90 of the pups. Age-matched control animals obtained regular tap water. Testes of control and Co-treated mice were processed for immunohistochemistry and inductively coupled plasma mass spectrometry. Sperm count was performed. RESULTS: Chronic CoCl2 administration resulted in significant dose-dependent Co accumulation in sera and testes of the exposed mice. Fe content also showed a significant increase in sera and testes compared to the untreated controls. Surprisingly, testes of low dose-treated mice had ∼ 2.7-fold higher Fe content compared to those exposed to the high dose. A significant dose-dependent reduction in relative testis weight by 18.8% and by 37.7% was found after treatment with low and high dose CoCl2, respectively was found. Our study demonstrated that developmental chronic exposure to CoCl2 affected cellular composition of the testis manifested by germ cell loss and low sperm count, accompanied by altered androgen response in Sertoli cells (loss of stage-specific expression of androgen receptor). A possible mechanism involved is iron accumulation in the testis that was associated with altered ferroportin-hepcidin localization in seminiferous tubules depleted in germ cells. As a protective mechanism for germ cells in condition of iron excess, ferroportin was distributed in Sertoli cells around elongating spermatids. Similar changes in expression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) implied that both factors of testicular Fe homeostasis are closely related. Outside the seminiferous tubules, Leydig cells localized ferroportin, hepcidin, DMT1 and TfR1 thus they could be considered as a main site for iron metabolism. CONCLUSION: Our data suggest that Co exerts its effects on the testis by indirect mechanism possibly through alteration in Fe homeostasis.

Assessment of the In Vitro and In Vivo Antitumor Activity of Hemocyanins from Helix aspersa, Helix lucorum, and Rapana venosa in a Graffi Myeloid Tumor Model.

Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of some invertebrate species that attracted scientific interest as potential anticancer agents. The present study aims to assess the in vitro and in vivo anticancer activity of hemocyanins isolated from Helix aspersa, Helix lucorum, and Rapana venosa in the Graffi myeloid tumor model. The in vitro antitumor activity of the hemocyanins was determined by a MTT test and cytomorphological analysis by fluorescent and transmission electron microscopy. The in vivo effects of the hemocyanins were examined in hamsters transplanted with Graffi tumor. The serum antibody titers against the tested hemocyanins and tumor antigen were determined by ELISA. Histopathological assessment of the morphological features related to antitumor effect, immune system response, and toxicity in some internal organs was performed. The results of in vitro studies indicated that the tested hemocyanins induced significant antiproliferative and apoptogenic effects. The in vivo investigations demonstrated a protective antitumor effect, expressed in reduced transplantability, suppression of tumor growth and metastasis, reduced mortality, prolonged survival time, and absence of toxic side effects. The present study indicated that the antitumor activity of the studied hemocyanins was due to both immune stimulation and direct effects on the tumor cells, and they displayed their potential as therapeutic agents against hematological malignances.

Effects of Salinomycin and Deferiprone on Lead-Induced Changes in the Mouse Brain.

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.

Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice.

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.

Modelling of chemical species of Al, Mn, Zn, and Pb in river body waters of industrial areas of West Rhodope Mountain, Bulgaria.

The assessment of the ecological status of natural surface water, in terms of dominant trace metals, within an area subject to various sources of pollution including a non-ferrous metal ore mining, such as the West Rhodope Mountain, Bulgaria, is significant. The present study estimates the ecological status of river body waters at industrial areas of the West Rhodope Mountain, Bulgaria, simultaneously evaluating the possibility of state forecasting, together with assessing the potential risks, through the study of scenarios focusing on (i) possible variations of physicochemical parameters such as pH, concentration levels of trace metals, sulphates, and dissolved organic carbon (DOC) of surface water and (ii) consideration of potential spontaneous precipitation reactions in the studied waters. The ecological status of river body waters was assessed through a combination of experimental field, laboratory, and computational techniques. Al, Mn, Zn, and Pb were found to be the dominant pollutants with a variety of chemical species and distribution. The most significant difference characterizing the chemical species distribution in light of total spontaneous crystallization in the systems was found for Pb, followed by Zn and Mn, with the differences being more significant at lower trace metal levels. The calculated species were discussed on the basis of HSAB (hard and soft acids and bases) principle.

Trace metals accumulation in the eco-system water - soil - vegetation (Agropyron cristatum) - common voles (Microtus arvalis) - parasites (Hymenolepis diminuta) in Radnevo region, Bulgaria.

BACKGROUND: Coal and coal processing industries provoke trace metal pollution, which has a negative effect on the water - soil - vegetation - small mammals eco-system, constituting part of the food chain and exerting a serious impact on human health. OBJECTIVES: Assessment of the environmental impact of Maritza iztok coal complex, situated east of Radnevo town, Bulgaria, by tracking the dynamics and accumulation of trace metals in the eco-system water - soil - vegetation - common voles - parasites. METHODS: Samples from surface waters, their nearby uncultivated soils, meadow uncultivated vegetation (Agropyron cristatum) and field common voles (Microtus arvalis) were collected. In situ measurements and laboratory extraction procedures and analyses were performed. Accumulation and mobility indices were calculated. The distribution of dissolved Mn, Ni, Cu, Zn and Pb chemical species in water-soil extracts was calculated using a thermodynamic approach. Two thermodynamic models were applied - the classical ion-association model for calculating the inorganic trace metal species and the Stockholm Humic Model (SHM) accounting for the complexation reactions of trace metals with organic matter. Visual Minteq computer program, Version 3.1 was used. The relationship chemical species - bioaccumulation was discussed. RESULTS: Pb and Mn, together with SO42- and PO43- were found to be the main pollutants of waters in the region. The soils studied exhibited low concentrations of trace metals, not exceeding the specified MACs. The content of Mn was the highest, followed by Zn, Pb, Cu and Ni. The highest phytoaccumulation coefficients in the studied uncultivated grass vegetation were calculated for Cu and Zn, being 1-2 orders of magnitude higher than those of Mn and Ni. The accumulation of trace metals was explained on the basis of ions mobility and chemical species distribution. In the case of the host-parasite system Microtus alvaris - Hymenolepis diminuta, Zn displays the highest accumulation coefficient, followed by those of Cu and Pb. The parasite showed a higher bioaccumulation compared to infected common voles, with the highest bioaccumulation found for Ni. CONCLUSIONS: The bioaccumulation of trace metals depends on their mobility, concentration and chemical forms in water-soil solutions. Metal-organic species stimulate the phytoaccumulation of trace metals while inorganic ones suppress it. The sequence of trace metals bioaccumulation in common voles is analogous to that of soil contamination. The parasite exhibited higher bioaccumulation levels compared to infected common voles.

Perinatal and early-life cobalt exposure impairs essential metal metabolism in immature ICR mice.

The objective of the present study was to assess the impact of cobalt (Co) exposure on tissue distribution of iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn), as well as serum hepcidin levels in immature mice (18, 25, 30 days). Pregnant mice were exposed to 75 mg/kg b.w. cobalt chloride (CoCl2 × 6H2O) with drinking water starting from 3 days before delivery and during lactation. At weaning (day 25) the offspring were separated and housed in individual cages with subsequent exposure to 75 mg/kg b.w. CoCl2 until 30 days postnatally. Evaluation of tissue metal levels was performed by an inductively coupled plasma-mass spectrometry (ICP-MS). Serum hepcidin level was assayed by enzyme linked immunosorbent assay (ELISA). Cobalt exposure resulted in a time- and tissue-dependent increase in Co levels in kidney, spleen, liver, muscle, erythrocytes, and serum on days 18, 25, and 30. In parallel with increasing Co levels, CoCl2 exposure resulted in a significant accumulation of Cu, Fe, Mn, and Zn in the studied tissues, with the effect being most pronounced in 25-day-old mice. Cobalt exposure significantly increased serum hepcidin levels only in day18 mice. The obtained data demonstrate that Co exposure may alter essential metal metabolism in vivo.

Alterations in Blood Metabolic Parameters of Immature Mice After Subchronic Exposure to Cobalt Chloride.

The wide use of cobalt (Co) in food, industry, and medical devices requires full elucidation of its biological effects on tissues and organs. The aim was to assess serum metabolic alterations in immature mice after subchronic exposure to CoCl2. Pregnant ICR mice were subjected to a daily dose of 75 mg cobalt chloride/kg body weight (CoCl2x6H2O) 2-3 days before they gave birth, and treatment continued until days 25 and 30 after delivery. The compound was dissolved in and obtained with regular tap water. ICP-DRC-MS analysis showed significantly elevated serum Co2+ and diverse alterations in metabolic parameters of 25- and 30-day-old pups after exposure to CoCl2. Cholesterol and urea levels were significantly elevated in day 25 mice while HDL-C and LDL-C were reduced. In day 30, Co-exposed mice LDL-C and triglycerides were significantly increased while the total cholesterol level remained unchanged. Alkaline phosphatase was significantly reduced in day 25 Co-exposed mice. Blood glucose level of Co-exposed mice remained close to the untreated controls. Total protein content was slightly increased in day 30 mice. Co-exposure reduced albumin content and albumin/globulin ratio but increased significantly globulin content. Co administration showed strong correlation with cholesterol, urea, and HDL-C in both day 25 and 30 mice. Inverse correlation was found with alkaline phosphatase and albumin for day 25 and with triglycerides, globulin, and total protein content in day 30 Co-exposed mice. Subchronic CoCl2 exposure of immature mice induced significant changes in key metabolic parameters suggesting possible further disturbances in energy metabolism, osteogenesis, and reproduction.

Cobalt accumulation and iron-regulatory protein profile expression in immature mouse brain after perinatal exposure to cobalt chloride.

Developing brain is very sensitive to the influence of environmental factors during gestation and the neonatal period. The aim of the study is to assess cobalt and iron accumulation in the brain as well as changes in the expression of iron-regulatory proteins transferrin receptor 1, hepcidin, and ferroportin in suckling mice. Perinatal exposure to cobalt chloride increased significantly cobalt content in brain tissue homogenates of 18-day-old (d18) and 25-day-old (d25) mice inducing alterations in brain iron homeostasis. Higher degree of transferrin receptor 1 expression was demonstrated in cobalt chloride-exposed mice with no substantial changes between d18 and d25 mice. A weak ferroportin expression was found in 18-day-old control and cobalt-treated mouse brain. Cobalt exposure of d25 mice resulted in increased ferroportin expression in brain compared to the untreated age-matched control group. Hepcidin level in cobalt-exposed groups was decreased in d18 mice and slightly increased in d25 mice. The obtained data contribute for the better understanding of metal toxicity impact on iron homeostasis in the developing brain with further possible implications in neurodegeneration.

Hemocyanins from Helix and Rapana Snails Exhibit in Vitro Antitumor Effects in Human Colorectal Adenocarcinoma.

Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins isolated from marine snail Rapana venosa (RvH) and garden snails Helix lucorum (HlH) and Helix aspersa (HaH), as well the mucus of H. aspersa snails, in the HT-29 human colorectal carcinoma cell line. The effects of the hemocyanins on the cell viability and proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alterations in the tumor cell morphology were examined by fluorescent and transmission electron microscopy. The results of the MTT assay showed that the mucus and α-subunit of hemocyanin from the snail H. aspersa had the most significant antiproliferative activity of the tested samples. Cytomorphological analysis revealed that the observed antitumor effects were associated with induction of apoptosis in the tumor cells. The presented data indicate that hemocyanins and mucus from H. aspersa have an antineoplastic activity and potential for development of novel therapeutics for treatment of colorectal carcinoma.

The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice.

The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2-3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

Dynamics of trace metals in the system water - soil - plant - wild rats - tapeworms (Hymenolepis diminuta) in Maglizh area, Bulgaria.

BACKGROUND: The impact of chemical elements on the biosphere is a function of their concentration and chemical form. Elucidation and prognosing of the latters in water basins and soil extracts is of particular significance for the assessment of their bioaccumulation in plants and animals. OBJECTIVES: Trace metals dynamics in the system water - soil-plant-wild rats - Hymenolepis diminuta in two agro-industrial zones (East and West) around Maglizh city, Bulgaria were investigated through experimental studies and thermodynamic modelling of the chemical species. METHODS: Samples from surface waters of rivers, their nearby uncultivated soils, meadow uncultivated vegetation (Ranunculus acris and Gramineae) and field rats were collected. In situ measurements and laboratory analyses were performed for the determination of the physico-chemical characteristics and total concentrations of Al, Fe, Mn, Ni, Cu, Zn and Pb. The distribution of their dissolved chemical species in water samples and in the aqueous soil extracts was calculated using a thermodynamic approach. The relationship chemical species - bioaccumulation was discussed. RESULTS: Waters and soils in the East zone of Maglizh area were found to be more polluted compared to those in the West one, regarding Ni, Mn, Zn, Pb and Cu, while Mn and Cu displayed the highest mobility in West zone soils. Trace metals contents in Ranunculus acris exceed that in Gramineae, since the highest accumulation factors were calculated for Cu and Zn. The highest accumulation in rats was found for Zn followed by Cu, being higher in the West zone. Thermodynamic modelling shows that Mn2+ free ions are dominant in both waters and aqueous soil extracts. Ni2+ and Zn2+ ions followed by metal-organic complexes are dominant in waters of East zone while metal-organic complexes followed by free ions are dominant in waters of West zone and both soil extracts. Metal-organic complexes are dominant for Fe, Cu and Pb in all samples studied, while mainly hydroxy forms (Al(OH)4-) followed by metal-organic complexes are typically for Al depending on pH. CONCLUSIONS: Experimentally established bioaccumulation of trace metals in the studied vegetation and rats is a consequence of the total concentration of trace metals in waters and soils, their mobility and chemical species. The dominance of organic complexes of trace metals is a prerequisite for their bioaccumulation in plants. Rats are in direct contact with the soil solution and therefore, of importance is the content of free ions of Mn2+, Ni2+, Zn2+, which are easily absorbed through the skin. The host-helminth system wild rat/H. diminuta could be used as a bioindicator for trace metals pollution.

Effect of acute sodium nitrite intoxication on some essential biometals in mouse spleen.

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.

Comparative study on the effects of salinomycin, monensin and meso-2,3-dimercaptosuccinic acid on the concentrations of lead, calcium, copper, iron and zinc in lungs and heart in lead-exposed mice.

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.

Ameliorative effect of the anticancer agent salinomycin on cadmium-induced hepatotoxicity and renal dysfunction in mice.

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.