Ameliorating effects of Raphanus sativus leaves on sodium arsenite-induced perturbation of blood indices in Swiss albino mice

Objective: To evaluate the ameliorating effects of Raphanus sativus leaves(RSL)against sodium arsenite(Sa)-induced adverse effects through mice experiments.Methods: Swiss albino mice were divided into four equal groups: control, Sa, RSL,RSL + Sa. Sa(10 mg/kg body weight/day), and powder form of RSL(50 mg/kg body weight/day) were provided as food supplement orallty. Blood indices were measured using commercially available kits through colorimetric methods.Results: It was observed that lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activities were significantly(P < 0.05)higher in Sa-treated mice than those in the control group. RSL significantly reduced Sainduced elevation of the activities of these enzymes in serum significantly(P < 0.05).Serum butyrylcholinesterase activity and high density lipoproteins cholesterol levels in Satreated mice were significantly(P < 0.05) lower than the control group, and the food supplementation of RSL could significantly(P < 0.05) prevent the reduction of Sa-mediated serum butyryl cholinesterase activity and high density lipoproteins cholesterol levels. RSL could also reduce the Sa-induced elevation of serum urea level significantly(P < 0.05).Conclusions: Results of this study suggest the protective or ameliorating effects of RSL on Sa-induced perturbation of blood indices are related to the hepatic, cardiovascular and kidney dysfunction. Therefore, RSL may be useful to reduce arsenic toxicity in human in the future.

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid（DMAV） is a major urinary metabolite of sodium arsenite（i As~Ⅲ） and induces urinary bladder cancers in rats. DMAVand i As~Ⅲare negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMAVand i As~Ⅲin rat urinary bladder epithelium and liver using gpt delta F344 rats.Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0,92 mg/L DMAV, or 87 mg/L i As~Ⅲ（each 50 mg/L As） for 13 weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection（gpt assay） and deletion mutations are identified in the red/gam genes by Spi-selection（Spi-assay）. Results of the gpt and Spi-assays showed that DMAVand i As~Ⅲhad no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAVand i As~Ⅲare not mutagenic in urinary bladder epithelium or liver in rats.

Microcalorimetric Study on the Effect of Sodium Arsenite on Metabolic Activity of Mitochondria Isolated from Carassius auratus Liver Tissue

Metabolic thermogenic curves of mitochondria isolated from liver tissue of Carassius auratus and the effect of different concentration of NaAsO2 on it were investigated by TAM air isothermal microcalorimeter, ampoule method, at 28.00 ℃. From the thermogenic curves, activity recovery rate constants k, the maximum heat production rate （Pmax） and the total heat produced （Q） were obtained. The values of k and Pmax decline gradually with the increase of the concentration of NaAsO2, and both of the values of Pmax and k are highly correlated to the concentration of NaAsO2. When concentration of NaAsO2 reached 16.0 μg/mL, the maximum heat production rate dropped to 70.8% of the control group, and the corresponding percentage of k was 71.4% of the control group. This experimental result indicates that the addition of NaAsO2 has restrained the metabolic activities of mitochondria in vitro.

Significant Phenomena Observed in the Molecule-Ion Adduct System of Sodium Arsenite with aoCyclodextrin

The data of 1H nuclear magnetic resonance and molar conductivity prove that there is a molecule-ion interaction between a-cyclodextrin （a-CD） and sodium arsenite （SA）, and the interaction site is different from that between β-CD and SA. The packing mode of a-CD molecules after adduct with SA is changed from cage to channel type. Several experimental phenomena from thermogravimetric analyses and gas chromatography coupled to time-of-flight mass spectrometry measurements reveal that the presence of SA has led to a large change of thermal decomposition behavior of a-CD, and vice versa. The current work reveals the particularity of the interaction between SA and a-CD, which would provide new insight into the understanding of molecule-ion interactions.

Effects of sodium arsenite on the expression of microRNA-191 and tissue inhibitor of metalloproteinase 3 in L-02 cells

Objective To investigate the effects of sodium arsenite（NaAsO2）on the expression of microRNA-191（miR-191）and tissue inhibitor of metalloproteinase 3（TIMP-3）in human normal hepatic cells（L-02 cells）.Methods L-02 cells were exposed to different doses of Na2As O2[0（control group）,5,25,50 and 75μmol/L]

PUB22 and PUB23 U-box E3 ubiquitin ligases negatively regulate 26S proteasome activity under proteotoxic stress conditions

The mechanism regulating proteasomal activity under proteotoxic stress conditions remains unclear.Here,we showed that arsenite-induced proteotoxic stress resulted in upregulation of Arabidopsis homologous PUB22 and PUB23 U-boxE3 ubiquitin ligases and that pub22 pub23 double mutants displayed arsenite-insensitive seed germination and root growth phenotypes.PUB22/PUB23 downregulated 26 S proteasome activity by promoting the dissociation of the 19 S regulatory particle from the holo-proteasome complex,resulting in intracellular accumulation of UbG76 VGFP,an artificial substrate of the proteasome complex,and insoluble poly-ubiquitinated proteins.These results suggest that PUB22/PUB23 play a critical role in arsenite-induced proteotoxic stress response via negative regulation of 26 S proteasome integrity.

MiADMSA minimizes arsenic induced bone degeneration in Sprague Dawley rats

Arsenic considered as one of the most hazardous chemical while arsenic poisoning is also one of the serious medical issues worldwide.Long term arsenic exposure is associated with bone degeneration.The exact mechanism involving arsenic induced bone degeneration remains unclear but,plentiful literature suggested that oxidative/nitrosative stress caused by generation of reactive oxygen species(ROS)and reactive nitrogen species(RNS)is one of the leading causes.Various treatment strategies are available for bone degeneration however,the suitable treatment for arsenic induced bone degeneration still lacks.In the current investigation,we evaluated the efficacy of chelation against arsenic induced bone degeneration in experimental rats.Male Sprague Dawley rats were exposed to sodium arsenite and dimethylarsinic acid(DMA)(50 ppm)for 18 weeks.After arsenic exposure,animals were treated with Monoisoamyl dimercaptosuccinic acid(MiADMSA)for three course of treatment(50 mg/kg,p.o.,once daily for 5 days)with an interval of one week between two courses of treatment.MiADMSA minimizes the bone degeneration through reduction of oxidative stress(Reactive Oxygen Species,Reactive Nitrogen Species,and thiobarbituric reactive substances),alteration of antioxidant status(rGSH,Superoxide dismutase,Catalase)which led to the depletion in the levels of inflammatory markers like TNFa and IL-1b and alteration in the bone remodelling biomarkers like ALP,RANKL,and Runx2.It can be concluded from this study that MiADMSA could be an effective therapeutic strategy against arsenic induced bone degeneration and the possible mechanism could be the chelation of arsenic accompanied by the reduction in oxidative stress and inflammation.