The present study deals with the therapeutic potential of combined administration of
N-acetylcysteine (NAC) along with monoisoamyl
DMSA (
MiADMSA) against chronic
arsenic poisoning in guinea pigs. Animal were exposed to 50 ppm
arsenic in
drinking water for 8 mo and subsequently treated for 5 consecutive days with 100 mg/kg NAC (orally) and
MiADMSA (intraperitoneally), individually or in combination (50 mg/kg each).
Arsenic exposure produced a significant depletion of blood
delta- aminolevulinic acid dehydrate (ALAD) activity, increased the blood
zinc protoporphyrin (ZPP) level, and reduced blood and liver
glutathione (GSH) levels in guinea pigs. Hepatic
oxidized glutathione (
GSSG) and
thiobarbituric acid reactive substance (
TBARS) levels showed a marked increase, whereas hepatic
alkaline phosphatase (ALP) activity decreased and
acid phosphatase (ACP) activity increased on
arsenic exposure. Significant depletion of liver
transaminase activities on
arsenic exposure suggests organ injury. Administration of
MiADMSA, alone and in combination with NAC after
arsenic exposure, was able to significantly enhance hepatic GSH and to reduce
GSSG and
TBARS levels compared to the
arsenic control. Biochemical variables indicative of liver injury generally remained insensitive to any of these treatments. The recoveries in parameters indicative of oxidative stress were more marked in guinea pigs treated with combined administration of NAC and
MiADMSA than monotherapy. Interestingly, there was a more pronounced depletion of
arsenic from blood and tissues after combined treatment with NAC plus
MiADMSA than
MiADMSA. Blood and tissues
copper,
zinc,
iron, and
calcium concentrations showed a significant increase after
arsenic exposure, which showed improvement, particularly after combined administration of
MiADMSA and NAC. Based on these data, a proposal can be made that greater effectiveness in chelation treatment against chronic
arsenic poisoning (i.e., turnover in the oxidative stress and removed of
arsenic from the system) could be achieved by combined administration of an
antioxidant (preferably having a
thiol moiety) with
MiADMSA.