Animals ; Arsenites ; therapeutic use ; Catheter Ablation ; Liver Neoplasms ; therapy ; Male ; Rabbits

OBJECTIVETo purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)).

METHODSArsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step.

RESULTSThe three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE.

CONCLUSIONThe three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

Administration, Oral ; Animals ; Arsenic ; blood ; Arsenites ; administration & dosage ; pharmacokinetics ; Carrier Proteins ; blood ; Chromatography, High Pressure Liquid ; methods ; Cricetinae

OBJECTIVETo explore whether there is difference in arsenicals-induced DNA damage of human lymphocyte.

METHODSLymphocyte were sterilely collected from healthy donor and exposed to sodium arsenite (AsIII), sodium arsenate(AsV) and methyl sodium arsenate(MAsv) at 1,5,10,20 and 50 mumol/L. After incubation of 24 hours, cells were collected by centrifugation and DNA damage was detected by single cell gel electrophoresis (SCGE).

RESULTSThe comet frequency distribution of all groups except 1 mumol/L group of MAsV were significantly different from that of control. The comet length of all groups except 1 mumol/L group of AsV and 1.5 mumol/L groups of MAsV were significantly higher than that of control. There were correlations between the doses of arsenicals and the ratios of comet cell or length of comet(rAsIII = 0.8134, rAsV = 0.8734, rMAsV = 0.8994).

CONCLUSIONDNA damage in human lymphocyte were induced by all the three arsenicals. A dose-effect relationship was observed between exposure doses of the same arsenical and DNA damage. With different arsenicals but the same exposure dose, the DNA damage level was as follow: AsIII > AsV > MAsV.

Arsenates ; toxicity ; Arsenites ; toxicity ; Comet Assay ; DNA Damage ; Dose-Response Relationship, Drug ; Humans ; Lymphocytes ; drug effects ; ultrastructure

OBJECTIVETo explore the clinical value of arsenious acid (H3AsO3) for treating patients with acute promyelocytic leukemia (APL).

METHODSA total of 86 patients with APL were randomly divided into experimental group (43 cases) and control group (43 cases). The control group was treated by all trans retinoic acid combined with chemotherapy, the experimental group were treated by arsenous acid on the basis of the control group.

RESULTSThe overall response rate (ORR) in experimental group (100.00%) was significantly higher than that in control group (88.37%) (P < 0.05). The time of returm to complete remission in experimental group (30.86 ± 4.34) was better than that in control group (42.42 ± 7.10) d (P < 0.05). The time of return to normal levels of peripheral WBC count (20.86 ± 9.28) × 10⁹/L, hemoglobin count (68.62 ± 14.97) g/L and thrombocyte count in experimental group obviously less than that in control group (P < 0.05). The rates of high white blood syndrome (HWBS), disseminated intravascular coagulation (DIC) in experimental group were lower than that in control group (P < 0.05). The survival rates of 2 and 3 years in experimental group were higher than that in control group (P < 0.05). The recurrence rate after treatment in experimental group was lower than that in control group (P < 0.05). The application of arsenious acid was main factor for patients survival (P < 0.05).

CONCLUSIONArsenious acid can improve the clinical efficacy for the patients with acute promyelocytic leukemia, and reduce the complication, therefore it is worthy of application in clinic.

Arsenites ; Disseminated Intravascular Coagulation ; Humans ; Leukemia, Promyelocytic, Acute ; Leukocyte Count ; Platelet Count ; Recurrence ; Remission Induction ; Survival Rate ; Tretinoin

In order to construct an Escherichia coli strain with high sensitivity and specificity to detect arsenic ion using fluorescence as reporter, a sensitive strain to arsenic ion was obtained by knocking out the gene arsB that acts as an arsenic efflux pump. The pET28b vector containing arsenite detecting cassette Pars-arsR-egfp was constructed and then transformed into arsB deleted mutant. Measuring conditions of this constructed whole-cell biosensor were optimized and its linear concentration range, limit of detection and specificity were determined. This modified biosensor was much more sensitive than that using wild-type strain as host. The optimal detection range of As³⁺ concentration was 0.013 to 42.71 μmol/L, and the limit concentration of detection was as low as 5.13 nmol/L. Thus we successfully improved the sensitivity of arsenite detecting biosensor by modification of E. coli genome, which may provide useful strategies for development and optimization of microbial sensors to detect heavy metals.
Arsenites ; analysis ; Biosensing Techniques ; Escherichia coli ; genetics ; Gene Knockout Techniques ; Metals, Heavy ; Microorganisms, Genetically-Modified ; Water ; chemistry

OBJECTIVETo evaluate the feasibility of establishing a mouse model of ovarian oxidative stress by intraperitoneal injections of arsenic sodium.

METHODSTwenty adult female Kunming mice were randomized equally into the normal control group and ovarian oxidative stress model group for intraperitoneal injections of 0.5 ml distilled water and 8 mg/kg arsenic sodium solution every other day, respectively. After 8 injections, the mice were sacrificed for histological observation of the ovarian sections and enzyme-linked immunosorbent assay (ELISA) of serum estradiol (E(2)) and pregnenedione (P) levels ande contents of reactive oxygen species (ROS) , malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the ovary homogenate.

RESULTSNumerous atretic follicles were found in the ovaries of mice in the model group with obviously reduced growing follicles. Compared with those in the normal control group, the contents of ROS and MDA increased and SOD and GSH-Px levels in the ovarian homogenate decreased significantly in the model group (P<0.05).

CONCLUSIONA mouse model of ovarian oxidative stress can be established by intraperitoneal injections of arsenic sodium.

Animals ; Arsenites ; Disease Models, Animal ; Female ; Glutathione Peroxidase ; analysis ; Malondialdehyde ; analysis ; Mice ; Mice, Inbred Strains ; Ovary ; metabolism ; physiopathology ; Oxidative Stress ; Reactive Oxygen Species ; analysis ; Superoxide Dismutase ; analysis

Arsenites ; toxicity ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Keratinocytes ; cytology ; Skin ; cytology ; Sodium Compounds ; toxicity

OBJECTIVETo study mechanism of the apoptosis of rat pancreas islet β cell strain (INS-1 cells) induced by sodium arsenite.

METHODSINS-1 cells were exposed to sodium arsenite at the different concentrations. MTT assay was used to detect the viability of INS-1 cells. The potentials on mitochondrial membrane and lysosome membrane of INS-1 cells were determined with the fluorescence spectrophotometer. The apoptotic levels of INS-1 cells exposed to sodium arsenite were observed by a fluorescence microscope and flow cytometry.

RESULTSAfter exposure to sodium arsenite, the viability of INS-1 cells significantly decreased with the doses of sodium arsenite. At 24 h after exposure, the OD values of the mitochondrial membrane potentials declined observably with the doses of sodium arsenite (P < 0.01). At 48 h after exposure, the OD values of the lysosome membrane potentials significantly increased with the doses of sodium arsenite (P < 0.01). At 72 h after exposure, the apoptotic cells were observed under a fluorescence microscope and enhanced with the doses of sodium arsenite. The apoptosis cells with light blue, karyopyknosis, karyorrhexis, apoptotic body and chromatin concentration appeared. The results detected with flow cytometry indicated that after exposure, the apoptotic INS-1E cells significantly increased with the doses of sodium arsenite.

CONCLUSIONSThe sodium arsenite can induce the apoptosis of INS-1 cells through the mitochondria-lysosome pathway.

Animals ; Apoptosis ; drug effects ; Arsenites ; toxicity ; Cells, Cultured ; Insulin-Secreting Cells ; drug effects ; Lysosomes ; metabolism ; Membrane Potentials ; drug effects ; Mitochondria ; metabolism ; Rats ; Sodium Compounds ; toxicity

OBJECTIVETo study the effects of sodium arsenite on gene expression related to growth and development and explored the molecular mechanism of arsenic effects using gene chips.

METHODSNormal human hepatic cells were dripped on chips and then hybrided with the first strand of cDNA from hepatic cell exposed to different concentration of sodium arsenite. Gene sequence of clone differently expressed was determined and then defined which gene it was and finally those genes which associated with growth and development were identified.

RESULTSThe p55 gene expression level of two experimental groups was severaly 2.21 and 2.93 times as the control group. The PL gene level of two experimental groups were 0.13 and 0.27 times as the control group, and the HOXA10 gene level was 0.22 and 0.35 times of the control group. These results indicated that sodium arsenite increase p55 gene expression, and inhibited PL and HOXA10 gene expression.

CONCLUSIONSThe sodium arsenite could affect the gene expression related to growth and development and it is shown that the molecular genetic mechanism of sodium arsenite is related to growth and development.

Arsenites ; poisoning ; Gene Expression ; drug effects ; genetics ; Hepatocytes ; cytology ; drug effects ; metabolism ; Humans ; Oligonucleotide Array Sequence Analysis ; methods ; Polymerase Chain Reaction ; Sodium Compounds ; poisoning

The effects of sodium arsenite exposure on the hepatic maturation period of cellular and functional reorganization in developing rat livers were evaluated. Animals received intraperitoneal injections of sodium arsenite (1.5 mg/kg body weight) or distilled water on days 9 to 28 after birth. On day 29, the animals were sacrificed either by cervical dislocation or by perfusion fixation. The perfusion fixed liver tissue was processed for paraffin embedding, sectioning and hematoxylin and eosin staining. The fresh liver tissue was processed for cryo-sectioning followed by Sudan Black B staining and for biochemical estimation of reduced glutathione. Microscopic observation revealed comparable preserved hepatic lobular patterns and distributions of uninucleate and binucleate hepatocytes in the control and the experimental groups. The mean nuclear area and diameter of the hepatocytes was increased in the experimental group. Lipid droplet distribution pattern in Sudan Black B stained sections revealed higher staining intensity towards the centrilobular area in both groups. Semiquantitative estimation of staining intensity showed lower mean gray values in zone 3 than in zones 2 and 1 (suggestive of the setting in of the adult pattern) in both groups. The reduced glutathione levels in the liver tissue and the altered nuclear size of the hepatocytes in the experimental group suggested the impairment of morphological and biochemical processes induced by arsenic exposure during the postnatal period.
Adult ; Animals ; Arsenic ; Arsenites ; Azo Compounds ; Biochemical Processes ; Dislocations ; Eosine Yellowish-(YS) ; Glutathione ; Hematoxylin ; Hepatocytes ; Humans ; Injections, Intraperitoneal ; Liver ; Paraffin Embedding ; Parturition ; Perfusion ; Rats ; Rats, Wistar ; Sodium ; Sodium Compounds ; Sudan ; Water