Arsenic induced inhibition of delta-aminolevulinate dehydratase activity in rat blood and its response to meso 2,3-dimercaptosuccinic acid and monoisoamyl DMSA.
OBJECTIVE
The objective of this study was to investigate arsenic induced changes in blood delta-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.
Bhadauria
Smrati
S
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474 002, India.
Flora
Swaran J S
SJ
D000284:Administration, Oral; D000818:Animals; D020261:Arsenic Poisoning / Q000097:blood*; D001152:Arsenicals / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000097:blood*; D051381:Rats; D004113:Succimer / Q000031:analogs & derivatives* / Q000494:pharmacology
D001152:Arsenicals; D004791:Enzyme Inhibitors; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D000623:Porphobilinogen Synthase