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The effectiveness of alpha-mercapto-beta-(2-furyl)acrylic acid (MFA) and N-benzyl-N-dithiocarboxy-D-glucamine (NaB), used in combination, in the mobilization and excretion of lead was investigated in rats. Male Wistar rats received 10 mg Pb/kg as lead acetate intragastrically daily for 6 weeks. The lead-exposed rats were treated with either MFA or NaB or both 200 mumol/kg i.p., each, daily for 3 days. Both chelating agents provoked significant urinary and faecal excretion and lowered the soft-organ lead burden. However, combined therapy did not elicit any additive or synergistic response.

alpha-Mercapto-beta-(2-furyl) acrylic acid (MFA), alpha-mercapto-beta-(phenyl) acrylic acid (MPA), alpha-mercapto-beta-(2-hydroxyphenyl) acrylic acid (MHA), alpha-mercapto-beta-(4-methoxyphenyl) acrylic acid (MMA), beta-1,2-phenylene di-alpha-mercapto acrylic acid (1, 2-PDMA) and beta-1, 4-phenylene di-alpha-mercapto acrylic acid (1, 4-PDMA) enhanced faecal excretion and reduced liver, spleen and blood burden of inorganic mercury when administered (0.5 m mol/kg, in two split doses) 24 hr after Hg (II) (1 mg/kg) in rats. MFA, MPA, MHA, and MMA were also effective in lowering renal Hg mainly from the cytosol, without any significant increase in urinary excretion of Hg. The results indicate that all the mono-mercapto acrylic acids including MFA were more effective than di-mercapto acrylic acids and act through the mechanism characteristic of thiol chelators, that is, mobilization of Hg as their complexes, contrary to the reported observation that MFA acts through the induction of metallothionein.

alpha-Mercapto-beta-(2-furyl) acrylic acid (MFA), alpha-mercapto-beta-(2-hydroxyphenyl) acrylic acid (MHA), beta-1,2-phenylene di-alpha-mercaptoacrylic acid (1,2-PDMA) and beta-1,4-phenylene di-alpha-mercapto acrylic acid (1,4-PDMA) were compared to sodium N-benzyl-D-glucamine dithiocarbamate (NBG-DTC) an effective cadmium chelator, for their ability to mobilize Cd and influence the Cd induced tissue metallothionein (MT) in rats administered 109CdCl2, 72 hr earlier. MFA was almost as effective as NBG-DTC but more effective than MHA in enhancing urinary and faecal excretion of Cd, reducing tissue and blood levels of Cd and in lowering Cd induced increase in hepatic and renal MT contents. 1,2-PDMA and 1,4-PDMA were effective only in reducing the hepatic burden of Cd. The resuls do not indicate any direct relationship between the efficacy of alpha-mercapto-beta-aryl acrylic acids to decorporate body Cd and their lipophilic-hydrophilic character or number-arrangement of their sulfhydryl groups.

beta-1,2-Phenylene di-alpha-mercaptoacrylic acid (1,2-PDMA), beta-1,4-phenylene di-alpha-mercaptoacrylic acid (1,4-PDMA) and alpha-mercapto-beta-(2-hydroxyphenyl) acrylic acid (MHA) were synthesized and compared with 2,3-dimercapto-propane-1-sulfonate (DMPS) for their ability to counteract toxic effects of lead and nickel in rats. 1,2-PDMA and DMPS were most effective in enhancing the excretion of metals, restoring most of the metal induced biochemical alterations and reducing the body burden of the metals; These observations confirm that the chelating agents with two adjacent sulfhydryl groups are better than those with non-adjacent SH groups as metal antidotes. The success of MHA in mobilizing the tissue metals and increasing their urinary excretion indicates participation of the hydroxy group on the benzene nucleus besides the SH group of the MHA molecule, in chelation of the metals.

In view of the reported effectiveness of alpha-mercapto-beta-(2-furyl) acrylic acid (MFA) as an effective antidote to inorganic mercury toxicity, some alpha-mercapto-beta-aryl acrylic acids were synthesized and examined for their efficacy in counteracting nickel and lead intoxication in rats. alpha-mercapto-beta-(3,4-dimethoxyphenyl)acrylic acid (MDA) was most effective and other compounds were less but about equally effective in enhancing urinary excretion and in reducing tissue concentration of Ni. MDA was the only compound to remove Ni from the brain. MFA was also more effective than other structurally related compounds in enhancing urinary and faecal excretion and in lowering body burden of Pb. All the compounds significantly reduced the inhibition of the activity of blood delta-aminolevulinic acid dehydratase (delta-ALA-D) and increase in the urinary excretion of delta-aminolevulinic acid (delta-ALA) caused by Pb. The results do not show any relationship between the nature of the substitution at the beta-position of alpha-mercapto acrylic acids and their ability to reduce the concentration and the toxic effects of the two metals. However, these thiol chelating agents appear promising as antidotes to Ni and Pb poisoning.