S.K. Tandon

Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or their combination in rat

The influence of an antioxidant agent such as N-acetyl cysteine (NAC) or mannitol on the cadmium chelating ability of monoisoamyl 2,3-dimercaptosuccinate (MiADMS) was investigated in cadmium pre-exposed rats. This ester of 2,3-dimercaptosuccinic acid (DMSA), an accepted drug for lead poisoning, being lipophilic in nature was expected to be an efficient cadmium chelator. The treatment of cadmium intoxicated animals with MiADMS reversed cadmium induced increase in blood catalase, superoxide dismutase (SOD) and malondialdehyde (MDA), liver MDA and brain SOD and MDA levels but not the decrease in blood, liver brain reduced glutathione (GSH) and increase in oxidized glutathione (GSSG) levels, consistent with the lowering of tissue cadmium burden. The administration of NAC or mannitol reversed the cadmium induced alterations in blood and liver GSH, GSSG, blood catalase, SOD, MDA, liver SOD, MDA and brain MDA levels without lowering blood and tissue cadmium contents. However, treatments with the combination of MiADMS and NAC or MiADMS and mannitol reversed these alterations as well as reduced blood and tissue cadmium concentrations. The combined treatment with MiADMS and mannitol was better than that with MiADMS and NAC, and was significantly more effective in normalizing blood, liver GSH, GSSG, brain GSSG, and their GSH/GSSG ratios than that by either of them alone. The combined treatments also improved liver and brain endogenous zinc levels, which were decreased due to cadmium toxicity. The results suggest that the administration of an antioxidant during chelation of cadmium may provide beneficial effects by reducing oxidative stress without its cadmium removing ability.

Comparative toxicity of trivalent and hexavalent chromium: Alterations in blood and liver

The effects of trivalent and hexavalent chromium compounds on rabbits were studied with a view toward investigating the toxic potentials of two different forms of chromium to which industrial workers or miners might be exposed. While both forms of chromium altered the levels of certain important chemical constituents of blood and serum and produced significant morphological changes in the liver, the hexavalent form induced a greater effect. The accumulation of the metal was also higher in animals exposed to chromium in oxidation state 6 than in those exposed to metal in state 3.

Beneficial effects of zinc supplementation during chelation treatment of lead intoxication in rats

The ability of zinc to enhance the efficacy of commonly used chelating drugs in lead intoxication and to reduce the resulting zinc imbalance, was investigated in rats. The simultaneous zinc supplementation increased urinary lead elimination by calcium disodium ethylenediaminetetraacetate (Ca disodium EDTA) and 2,3 dimercaptosuccinic acid (DMSA). Combination therapy was also effective in potentiating the depletion of blood, hepatic and renal lead by calcium disodium EDTA and D-penicillamine (DPA), renal lead by DMSA and reversal of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity by calcium disodium EDTA and DPA. The body zinc status was also maintained as reflected by urinary, blood and tissue levels of zinc.

Lead poisoning in Indian silver refiners.

The refining of silver from old silver ornaments, articles and jewellers waste by smelting these with lead scraps for the fabrication of new jewellery is an important small scale industry in India. The present survey and clinical investigations have shown that 31 out of 50 silver refiners with a mean blood lead level of 32.84+/-1.78 microg/dl (range 20.3-64.9), decrease in blood delta-aminolevulinic acid dehydratase (ALAD) activity and thiamine (as pyruvate) level and an enhanced urinary excretion of ALA as compared to control, were suffering from lead poisoning. Most of these workers have shown anaemia, abdominal colic, blue lining of gum and muscular wasting indicative of lead toxicity. Twenty-four workers with relatively high blood lead levels were equally divided into two groups and given either vitamin B1 (75 mg, once a day) or vitamin C (250 mg. twice a day) for 1 month. The treatment with both the vitamins significantly lowered the blood lead levels and reduced blood thiamine and copper deficiency. In addition, vitamin C was also effective in reversing the inhibition of blood ALAD activity while the effect of vitamin B1 on its activity was marginal. The daily intake of vitamin B1 and vitamin C may prevent the accumulation of lead and reduce its toxic effects particularly in those regularly exposed to lead.

Effect of combined exposure to lead and ethanol on some biochemical indices in the rat

We investigated the effect of daily oral administration to young rats of lead (10 mg/kg) and ethanol (10%, v/v, in drinking water), either alone or in combination, for 8 weeks on the uptake of lead in tissues, brain biogenic amines, hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase and some selected lead-sensitive variables. Lead given in combination with ethanol produced more pronounced inhibition in the activities of hepatic glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) as compared to lead alone treatment. Simultaneous exposure to lead and ethanol produced a greater depression of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the whole brain of rats, compared to rats treated with lead alone. The concentrations of lead in blood, liver and brain were significantly higher in rats exposed simultaneously to lead and ethanol. Though ethanol treatment alone inhibited the activities of hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase, no effect of lead treatment alone on these variables was observed. The results suggested that animals exposed to ethanol and lead are more vulnerable to the neurologic and hepatotoxic effects and the systemic toxicity of lead.

Protective role of trace metals in lead intoxication.

Protective effect of copper (Cu), zinc (Zn) or cobalt (Co) against lead (Pb) toxicity in rats was investigated. Trace metal administration together with Pb decreased the hepatic and renal uptake of lead and reduced the Pb-induced inhibition of blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. The hepatic uptake of Zn or Co was also increased in animals administered Pb and Zn or Pb and Co, respectively. However, no significant difference could be observed between the protective effects of three essential trace metals examined against lead toxicity.

Thiamine and Zinc in Prevention or Therapy of Lead Intoxication

Thiamine, zinc or their combination given through gastric gavage were investigated for their ability to prevent or treat experimental lead toxicity in rats. Simultaneous dietary supplementation with thiamine plus zinc was found to be the most effective way of reducing the lead-induced inhibition of δ-aminolevulinic acid dehydratase activity in blood, urinary excretion of δ-aminolevulinic acid and accumulation of lead in blood, liver and kidney. Prevention was more effective than post-lead exposure treatment which may be due mainly to the decrease in the absorption of lead in the gastro-intestinal tract in the presence of thiamine and/or zinc.

Comparative toxicity of trivalent and hexavalent chromium to rabbits. II. Morphological changes in some organs.

Toxicity of trivalent and hexavalent chromium compounds was investigated in experimental rabbits to ascertain health hazards among industrial workers of miners occupationally exposed to such chemicals. Brain, kidney and myocardium showed a tendency to accumulate chromium irrespective of its valency state; the morphological changes were more marked in animals exposed to hexavalent chromium. However, no definite co-relation could be observed between the concentration of the metal and the degree of histological changes in these organs.

Influence of thiamine and ascorbic acid supplementation on the antidotal efficacy of thiol chelators in experimental lead intoxication

The influence of the administration of thiamin (vitamin B1), ascorbic acid (vitamin C) or their combination on the efficacy of two thiol metal chelators, viz. α-mercapto-β-(2-furyl) acrylic acid (MFA) and 2,3-dimercaptosuccinic acid (DMS), in counteracting lead (Pb) toxicity was investigated in rats. Ascorbic acid or its combination with thiamine enhanced the urinary elimination of Pb, reduced the hepatic and renal burden of Pb, and reversed the Pb-induced inhibition of the activity of blood 5-aminolevulinic acid dehydratase (δ-ALA-D). All these effects were more evident in DMS- than in MFA-treated rats. The combination of MFA and DMS treatments further improved the performance of the animals in enhancing urinary Pb excretion and in reducing Pb hepatic levels.

Time-dependent protective effect of selenium against cadmium-induced nephrotoxicity and hepatotoxicity.

The role of selenium in protection against nephrotoxicity and hepatotoxicity of cadmium in rats was investigated. The administration of Cd (3 mg/kg, s.c.) for 3 days enhanced the urinary excretion of lactic dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) and total proteins, decreased the renal activity of GOT and alkaline phosphatase (ALP) and increased the renal level of Cd, Cu and Zn. Cadmium also increased the serum GOT and glutamic pyruvic transaminase (GPT), decreased the hepatic activity of GOT and GPT and increased the hepatic level of Cd and Zn. The concomitantly administered Se (2 mg/kg, i.p.) initially reduced most of these Cd-induced alterations. The results show protection by Se against nephrotoxicity and hepatotoxicity of Cd on the 4th day of the commencement of Cd administration, but the signs of Cd intoxication were observed on the 8th day.