Ascorbic Acid Supplementation Does Not Improve Efficacy of meso‐Dimercaptosuccinic Acid Treatment in Lead‐Exposed Suckling Rats

Abstract

It was suggested that ascorbic acid as a natural chelating agent can influence lead toxicokinetics and improve chelating properties of dimercaptosuccinic acid (DMSA) in adult rats. In this paper potential benefits of ascorbic acid supplementation, alone or combined with DMSA, in decreasing lead retention in suckling rats were evaluated. Such data in young mammals are not available. L-Ascorbic acid (daily dose 650 mg/kg b.wt.) and/or DMSA (daily dose 91 mg/kg b.wt.) were administered orally to suckling Wistar rats either during ongoing 8-day oral lead exposure (as acetate; daily dose 2 mg lead/kg b.wt.) or after 3-day lead exposure (total dose 12 mg lead/kg b.wt.). Lead concentrations were analysed in the carcass (skeleton), liver, kidneys and brain by atomic absorption spectrometry. By ascorbic acid supplementation lead retention was not reduced under either lead exposure condition. Lead concentration was even increased in the carcass. Treatment with DMSA under both exposure conditions significantly reduced lead in all analysed tissues. Combined treatment with ascorbic acid and DMSA during ongoing lead exposure was substantially less effective than DMSA treatment alone, and did not affect DMSA efficacy when administered after lead exposure. It was concluded that ascorbic acid administered either during or after lead exposure in suckling rats has no beneficial effect on either lead retention or DMSA chelation effectiveness.

Therapeutic potentials of combined use of DMSA with calcium and ascorbic acid in the treatment of mild to moderately lead intoxicated mice

“…On the other hand, it was reported that treatment with ascorbic acid could result in amelioration of oxidative stress without a significant decline in tissue lead burden (Patra et al 2001;Simon and Hudes 1999). Studies reported by Flora et al (2003) and Varnai et al (2003) showed that when ascorbic acid was given along with DMSA, it was capable of reversing lead-inhibited activities of blood ALAD compared to DMSA given alone, however, combined use of ascorbic acid and DMSA during lead exposure was substantially less effective than DMSA treatment alone, and did not affect DMSA chelating efficacy when administered after lead exposure. Our findings suggested supplementation of DMSA with calcium and ascorbic acid after lead exposure could achieve pronounced therapeutic efficacies in depleting tissue lead and ameliorating activities of blood ALAD compared to DMSA given alone.…”

“…Beneficial effects of ascorbic acid in the treatment of lead poisoning could be attributed to its ability to scavenge free radicals and form complexes with lead, thereby, curtailing lead-induced oxidative stress and decreasing intestinal absorption as well as increasing renal lead clearance (Dalley et al 1990;Houston and Johnson 2000;Gurer and Ercal 2000;Kleszczewska 2001;Upasani et al 2001;Hsu and Guo 2002;Shalana et al 2005). Although the beneficial effects of DMSA, calcium or ascorbic acid in the treatment of lead poisoning have been well-testified, the therapeutic potentials of calcium and ascorbic acid in conjunction with DMSA in chelating therapy of lead poisoning has not been extensively studied, except for a few reports on combined use of DMSA with calcium or ascorbic acid alone (Varnai et al 2003(Varnai et al , 2004Flora et al 2003). Consequently, the objective in present study was to explore the therapeutic potentials of DMSA used with calcium and ascorbic acid in the treatment of mild to moderately lead intoxicated mice.…”

Vitamin C modulates lead excretion in rats

“…Chelating agents that are used to cure lead poisoning include mesodimercaptosuccinic acid (DMSA), dimercaptopropan-1-sulphonate, and ethylendiamine tetraacetic acid [8, 9]. Chelating agents couple with heavy metals, such as lead and mercury, and enhance their excretion in sweat and urine.…”

“…It is estimated in the study of rabbit's renal cortex that vitamin C prevents the accumulation of paraquat by the ascorbic acid mediated transmembrane-reducing system [10]. Also, it has been reported that vitamin C does not increase the impact of DMSA in the rat exposed to lead [9], but there have been few data about human subjects. Simon et al examined the relationship between vitamin C and lead in blood by conducting cross-sectional study against 4,213 children from 1988 to 1994.…”

“…It has been reported also that the use of vitamin C with thiol chelators such as DMSA reduces oxidative stress significantly [14-16], although it is no more effective than the treatment with thiol chelator only [9, 14]. …”