Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats.
We compared the therapeutic efficacy of captopril and a thiol chelating agent, meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination against arsenite induced oxidative stress and mobilization of metal in rats. Animals were exposed to 100 ppm arsenite as sodium arsenite in drinking water for six weeks followed by treatment with DMSA (50 mg/kg, orally), captopril (50 mg/kg, intraperitoneally) either alone or in combination, once daily for 5 consecutive days. Arsenite exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione and platelet levels while significantly increased the level of reactive oxygen species (in RBCs). Hepatic reduced glutathione (GSH) level showed a significant decrease while, thiobarbituric acid reactive substances (TBARS) levels increased on arsenite exposure indicating arsenite induced hepatic oxidative stress. Kidney GSH, GSSG, catalase and TBARS remained unchanged on arsenite exposure. Treatment with DMSA was effective in increasing ALAD activity while, captopril was ineffective when given alone. Captopril when co-administered with DMSA also provided no additional beneficial effect on blood ALAD activity but significant brought altered platelet counts back to the normal value. In contrast, administration of captopril alone provided significant beneficial effects on hepatic oxidative stress, and in combination with DMSA provided a more pronounced recovery in the TBARS level compared to the individual effect of DMSA and captopril. Renal biochemical variables remained insensitive to arsenite and any of the treatments. Interestingly, combined administration of captopril with DMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that captopril administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity, and depletion of arsenic level. The study supports our earlier conclusion that a co-administration of an antioxidant is more beneficial than monotherapy with the chelating agents, in order to achieve optimal effects of chelation in arsenite toxicity.
Kalia
Kiran
K
Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar-388001, Gujarat, India.
Narula
Gagan Deep
GD
Kannan
G M
GM
Flora
S J S
SJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001151:Arsenic / Q000097:blood / Q000378:metabolism; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D004347:Drug Interactions; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D000623:Porphobilinogen Synthase / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D004113:Succimer / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000931:Antidotes; D000975:Antioxidants; D018053:Arsenites; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D003300:Copper; D002216:Captopril; D004113:Succimer; D000623:Porphobilinogen Synthase; D005978:Glutathione; D015032:Zinc; C015001:arsenite; D001151:Arsenic; D019803:Glutathione Disulfide