ABSTRACT
OBJECTIVE: To synthesize some new alpha-mercapto-beta-substituted aryl acrylic acids, characterize them and investigate their in vitro cadmium chelating ability. METHODS: Six alpha-mercapto-beta-substituted aryl acrylic acids were prepared by the alkaline hydrolysis of 5- (aryl methylene) rhodanines, obtained from the condensation of substituted aldehydes and rhodanine following the reported procedure. The new compounds were characterized by elemental analysis, infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The liver and kidney from cadmium chloride pre-administered rats were homogenized and their nuclear mitochondrial fraction (NMF) and supernatant cytosol fraction (SCF) were separated. A measured volume of each fraction was dialyzed separately using "dialysis sack" against buffered-KCl medium containing a compound in the final concentration of 1 x 10(-3) mol/L for 3 h at 37 degrees C. The whole content of "sack" was subjected to cadmium estimation following digestion with conc. Nitric acid was detected using flame atomic absorption spectrometer. RESULTS: The in vitro screening showed that alpha-mercapto-beta-(p-methoxyphenyl) acrylic acid (compound 2) and alpha-mercapto-beta-(m-methoxy, p-hydroxyphenyl) acrylic acid (compound 4) were more effective than alpha-mercapto-beta-thienyl acrylic acid (compound 1) and alpha-mercapto-beta-(p-dimethylaminophenyl) acrylic acid (compound 3) in mobilizing cadmium as their dialyzable chelates. The presence of a methoxy group on the phenyl moiety (compounds 2 and 4) increases the metal chelating ability of mercapto acrylic acids. CONCLUSIONS: Compounds 2 and 4 seem to have accessibility to the cellular system and capability of chelating-out the intracellularly bound cadmium.
Subject(s)
Acrylates/chemical synthesis , Cadmium Chloride/metabolism , Chelating Agents/chemical synthesis , Mitochondria/metabolism , Sulfhydryl Compounds/chemical synthesis , Acrylates/chemistry , Acrylates/pharmacology , Animals , Cadmium Chloride/toxicity , Chelating Agents/chemistry , Chelating Agents/pharmacology , Injections, Intraperitoneal , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Male , Mitochondria/drug effects , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Rats , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacologyABSTRACT
Influence of age on lead-induced oxidative stress was investigated in young, adult, and old rats maintained on 0.2% lead acetate (2000 ppm lead) in drinking water for 3 mo. The lead-induced depletion of blood and liver reduced glutathione was about equal in young and adult but not in old rats. The increases in blood, liver, and brain oxidized glutathione and blood and liver superoxide dismutase levels were related to the accumulation of lead in these tissues and followed the order young > adult > old. The lead-induced inhibition of blood delta-aminolevulinic acid dehydratase activity, lowering in hemoglobin, and enhanced urinary excretion of delta-aminolevulinic acid were independent of variation in age. The results indicate that young rats may be most sensitive, whereas old rats may be most resistant to some of the oxidative effects of lead examined, which may be related to the accumulation of lead.
Subject(s)
Aging/metabolism , Lead/toxicity , Oxidative Stress , Animals , Brain/metabolism , Glutathione/blood , Glutathione/metabolism , Lead/blood , Lead/metabolism , Liver/enzymology , Liver/metabolism , Male , Porphobilinogen Synthase/antagonists & inhibitors , Porphobilinogen Synthase/blood , Rats , Superoxide Dismutase/blood , Superoxide Dismutase/metabolismABSTRACT
The influence of cysteine or N-acetyl cysteine administration on the efficacy of 2,3-dimercaptopropane-1-sulphonate (DMPS) in the treatment of cadmium intoxication was investigated in cadmium-pre-exposed rats. Cysteine, N-acetyl cysteine, DMPS, DMPS + cysteine or DMPS + N-acetyl cysteine were about equal in effectiveness in mobilizing hepatic cadmium mainly from its supernatant cytosolic fraction (SCF) and both of the combinations were more effective than either of them alone in mobilizing cadmium from its nuclear mitochondrial fraction (NMF). The DMPS was apparently more effective than cysteine or N-acetyl cysteine in mobilizing renal cadmium from its SCF or NMF and it was more effective than even their combinations in mobilizing cadmium from renal SCF. The treatment with cysteine or N-acetyl cysteine reduced cadmium-induced hepatic and renal metallothionein (MT) and the treatment with DMPS reduced renal MT only, probably due to removal of hepatic and renal SCF cadmium by these agents. However, MT levels were high in animals treated with DMPS + cysteine or DMPS + N-acetyl cysteine, despite lowering of cadmium in these tissues, suggesting a contribution of MT induced by cysteine or N-acetyl cysteine itself. The cadmium exposure increased hepatic and renal zinc and renal copper levels, probably as a result of cadmium-induced MT, and some of the levels were normalized considerably by the subsequent treatment with cysteine, DMPS or to a lesser extent N-acetyl cysteine and their combinations, showing their protective effects against cadmium toxicity. The increase in blood cadmium and the decrease in blood zinc and copper levels due to cadmium exposure also were reversed appreciably by some of these treatments. The results have shown a limited benefit of cysteine or N-acetyl cysteine administration on the efficacy of DMPS in the treatment of cadmium intoxication.
