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Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats.

Abstract

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.

Authors+Show Affiliations

Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar-388001, Gujarat, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17188940

Citation

Kalia, Kiran, et al. "Effects of Combined Administration of Captopril and DMSA On Arsenite Induced Oxidative Stress and Blood and Tissue Arsenic Concentration in Rats." Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, vol. 144, no. 4, 2007, pp. 372-9.
Kalia K, Narula GD, Kannan GM, et al. Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats. Comp Biochem Physiol C Toxicol Pharmacol. 2007;144(4):372-9.
Kalia, K., Narula, G. D., Kannan, G. M., & Flora, S. J. (2007). Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats. Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, 144(4), pp. 372-9.
Kalia K, et al. Effects of Combined Administration of Captopril and DMSA On Arsenite Induced Oxidative Stress and Blood and Tissue Arsenic Concentration in Rats. Comp Biochem Physiol C Toxicol Pharmacol. 2007;144(4):372-9. PubMed PMID: 17188940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats. AU - Kalia,Kiran, AU - Narula,Gagan Deep, AU - Kannan,G M, AU - Flora,S J S, Y1 - 2006/11/17/ PY - 2006/04/25/received PY - 2006/11/14/revised PY - 2006/11/14/accepted PY - 2006/12/26/pubmed PY - 2007/5/26/medline PY - 2006/12/26/entrez SP - 372 EP - 9 JF - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JO - Comp. Biochem. Physiol. C Toxicol. Pharmacol. VL - 144 IS - 4 N2 - 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. SN - 1532-0456 UR - https://www.unboundmedicine.com/medline/citation/17188940/Effects_of_combined_administration_of_captopril_and_DMSA_on_arsenite_induced_oxidative_stress_and_blood_and_tissue_arsenic_concentration_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1532-0456(06)00243-2 DB - PRIME DP - Unbound Medicine ER -