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 ...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.展开更多
Objective The objective of this study was to investigate arsenic induced changes in blood 8-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administrat...Objective The objective of this study was to investigate arsenic induced changes in blood 8-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1,0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1,0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value. Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.展开更多
文摘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.
文摘Objective The objective of this study was to investigate arsenic induced changes in blood 8-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1,0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1,0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value. Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.
