Combined administration of a chelating agent and an antioxidant in the prevention and treatment of acute lead intoxication in rats.
The administration of chelating agents, meso 2,3-dimercaptosuccinic acid (DMSA), monoisoamyl DMSA (MiADMSA) either individually or in combination with an antioxidant, n-acetylcysteine (NAC) in the prevention and treatment of acute lead intoxication in rats, was investigated. The results suggest that concomitant oral supplementation of DMSA with lead was most effective in preventing the inhibition of lead sensitive blood delta-aminolevulinic acid dehydratase (ALAD) activity in blood, elevation of zinc protoporphyrin level and the alterations in hepatic reduced and oxidized glutathione (GSH and GSSG) contents. A number of other biochemical variables either remained insensitive to lead exposure or responded moderately to chelation treatment. Combined administrations of NAC plus DMSA was most effective when given during lead exposure or post exposure, followed by DMSA and MiADMSA alone or NAC plus MiADMSA treatment, in reducing the accumulation of lead in blood and liver. Administration of NAC alone was only mildly effective in preventing lead absorption in the blood and tissues. The results suggest that combined administration of DMSA and NAC could be a more effective treatment protocol for acute lead toxicity, keeping in view its beneficial effect on oxidative injury.
Pande
M
M
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, 474 002, Gwalior, India
Mehta
A
A
Pant
B P.
BP
Flora
S J.S.
SJ