The dose dependent effects of monoisoamyl and monomethyl
esters of meso
2,3-dimercaptosuccinic acid (
DMSA) (0.1, 0.3 and 0.5 mmol kg(-1), intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of
gallium arsenide and the mobilization of
gallium and
arsenic were examined. The effects of these
chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg(-1),
GaAs, orally once daily for 12 weeks and were administered
DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days.
DMSA was used as a positive control.
DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of
chelation therapy in
GaAs pre-exposed rats,
MiADMSA was most effective in the reduction of inhibited blood
delta-aminolevulinic acid dehydratase (ALAD) activity and
zinc protoporphyrin level while, all three
chelators effectively reduced urinary ALA excretion, compared to
GaAs alone exposed rats.
MiADMSA was also effective, particularly at a dose of 0.3 mmol kg(-1), in enhancing the inhibited hepatic
transaminase activities. Parameters indicative of oxidative stress responded less favorably to the
chelation therapy, however, three
chelators significantly restored the altered immunological variables.
MiADMSA was relatively more effective than the other two
chelators.
GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three
chelators significantly reduced
arsenic concentration and, however,
MiADMSA was more effective than the other two
chelators in depleting
arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg(-1) was found to be relatively better than the other two doses examined.
Gallium contents of blood and soft tissues remained uninfluenced by the
chelation therapy. Significant loss of
copper after
MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose,
duration of treatment and possible toxic/side effects. Keeping in view the promising role of
MiADMSA in the treatment of
GaAs poisoning, these data will be needed for the registration of this
chelating agent as licensed
drug for the treatment of
gallium arsenide intoxication.