Comparative effects of single and combined chelation therapy in chronic lead toxicity: role of reactive oxygen species

ABSTRACT

To investigate and compare the efficacy of different chelation therapies either single [CaNa[2]EDTA or meso-DMSA] or combined regimen [CaNa[2]EDTA + meso-DMSA] in the treatment of chronic lead acetate exposure and suggested role of reactive oxygen species [ROS] in the mechanism of lead toxicity. This study was carried out on thirty adult male albino rats classified into 5 groups [6 rats/each group] and subjected to the treatments with lead acetate in a dose of 5mg/kg daily for 6 weeks [i.p] for 6 weeks, then injected with CaNa[2]EDTA [0.3 mmol/kg daily, i.p.] for 2 consecutive weeks or meso-DMSA [0.5 mmol/kg daily, i.p.] for 2 consecutive weeks or both CaNa[2]EDTA 0.3 mmol/kg daily, [i.p.] and meso-DMSA [0.5 mmol/kg daily, i.p.] for 2 consecutive weeks. Lead was estimated by flame atomic absorption spectrometry, serum thiobarbituric acid reactive substances [TBA-RS], tissue TBA-RS, serum protein thiols [PrSH], tissues non-protein sulfhydryl compounds [NPSH], hemoglobin and serum creatinine were determined spectrophotometry. Brain glutathione peroxidase [GPx] was determined by high performance liquid chromatography [HPLC].Treatment of adult male albino rats with lead acetate produced significant increases in lead levels of serum, liver, kidney, brain and bone amounting to 205%, 126%, 152%, 275% and 133%, respectively as compared to control healthy group. Also, there were marked elevations in thiobarbituric acid reactive substances [TBA-RS] which are indicators of oxidative stress in serum, liver, kidney and brain calculated as 159%, 95%, 192% and 153%, respectively. In addition, serum protein thiol [PrSH] was decreased amounted to 32%. Meanwhile, there was marked decrease in non-protein sulfhydryl groups [NPSH] of kidney reaching 36%. Moreover, measured serum creatinine was significantly elevated recording 245%, whereas hemoglobin concentration was markedly decreased amounted as 23% in comparison with the control group. On the other hand, administration of each of the single chelating agents [calcium disodium ethylenediaminetetraacetic acid, CaNa[2]EDTA, i.p. in a dose of 0.3 mmol/kg daily for 2 consecutive weeks or meso-dimercaptosuccinic acid, meso-DMSA, i.p. in a dose of 0.5 mmol/kg daily for 2 consecutive weeks] and the combined chelation therapy [CaNa[2]EDTA 0.3 mmol/kg daily, i.p. and meso-DMSA 0.5 mmol/kg daily, i.p] for 2 consecutive weeks after lead acetate treatment resulted in significant ameliorating effects in the previous mentioned parameters. It is to be concluded that the reactive oxygen species play important roles in chronic lead toxicity. Moreover, each of meso-DMSA or the combined chelation therapy is more effective than CaNa[2]EDTA in reducing serum and brain lead levels as well as brain TBA-RS. However, the combined chelation therapy was more effective than meso-DMSA in decreasing serum TBA-RS; Effects that might be considered on choice of such chelating agents during chronic lead intoxication