Quercetin administration during chelation therapy protects arsenic-induced oxidative stress in mice.
We studied the efficacy of quercetin and a thiol chelating agent, monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) either individually or in combination against arsenic-induced oxidative stress and mobilization of metal in mouse. Animals were chronically exposed to 25 ppm arsenite as sodium arsenite in drinking water for 12 months followed by treatment with MiADMSA (0.2 mmol/kg, orally), quercetin (0.2 mmol, orally) either alone or in combination, once daily for 5 consecutive days. Arsenic exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione, white (WBC) and red blood cell (RBC) counts, and an increase in platelet levels while significantly increasing the level of reactive oxygen species (in RBCs). Hepatic reduced catalase (CAT) and glutathione peroxidase activities showed a depletion, whereas thiobarbituric acid reactive substances (TBARS) levels increased on arsenic exposure indicating arsenite-induced oxidative stress in blood and liver. Kidney CAT activity showed a depletion, whereas TBARS levels increased on arsenic exposure. These biochemical changes were accompanied by an increase in blood, liver, and kidney arsenic concentration. Treatment with MiADMSA was effective in increasing ALAD activity, whereas quercetin was ineffective when given alone. Quercetin when co-administered with MiADMSA also provided no additional beneficial effect on blood ALAD activity but significantly brought altered platelet counts nearer to the normal value. In contrast, administration of quercetin alone provided significant beneficial effects on hepatic oxidative stress and kidney TBARS levels. Renal biochemical variables remained insensitive to arsenic and any of the treatments. Interestingly, combined administration of quercetin with MiADMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that quercetin administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity and depletion of arsenic level from target organs. The study supports our earlier conclusion that a co-administration of an antioxidant particularly flavonoids more beneficial than monotherapy with the chelating agents to achieve optimal effects of chelation in arsenite toxicity.
Mishra
Deepshikha
D
Division of Pharmacology and Toxicology, Defense Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India.
Flora
S J S
SJ
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D001151:Arsenic; D015913:Chelation Therapy / Q000379:methods*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D004113:Succimer / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D000975:Antioxidants; D017382:Reactive Oxygen Species; D011794:Quercetin; D004113:Succimer; D000623:Porphobilinogen Synthase; D005978:Glutathione; D001151:Arsenic