S-adenosyl-L-methionine: its effect on aminolevulinate dehydratase and glutathione in acute ethanol intoxication.

The effect of disulfiram and S-adenosyl-L-methionine (SAM) administration to acute ethanol intoxicated mice on the hepatic glutathione (GSH) concentration and aminolevulinic and dehydratase (ALA-D) activity was investigated. It was found that both GSH levels and ALA-D activity were decreased, and evidence suggested that the toxic action of ethanol was due to its conversion into acetaldehyde. Administration of SAM reverses the effects of acute alcohol abuse by increasing liver GSH availability. In vitro, hepatic ALA-D activity was not modified by ethanol; instead it was non-competitively inhibited by acetaldehyde. This inhibition was efficiently reversed by GSH and cysteine (CySH). Therefore, a mechanism for the action of ethanol on ALA-D, based on the inhibitory effect of acetaldehyde, is proposed.

S-adenosyl-L-methionine a counter to lead intoxication?

The effect of S-adenosyl-L-methionine (SAM) administration to both acute and chronic lead exposed mice was investigated. SAM was given s.c. at different doses and for different time intervals. The best results were obtained using 20 mg SAM/kg applied daily over a period of 20-22 days. Results obtained in both acute and chronic lead poisoning were quite similar. GSH concentration in blood and liver, reduced in intoxicated animals was increased after SAM administration reaching normal values. Blood, liver and kidney lead content notably increased at the beginning of SAM treatment and decreased rapidly in the group receiving SAM, attaining values near control levels in 2 weeks. A significant recovery of blood, liver, kidney, spleen and brain delta-aminolevulic acid dehydratase (ALA-D) initially reduced in poisoned animals, was clearly produced after SAM administration. A clear and direct correlation between the recovery of both ALA-D activity and GSH levels and the decreased concentration of lead in tissues was observed, reinforcing our proposal that enhancement of thiol content as a result of SAM administration would facilitate the detoxification process and lead removal, consequently reversing the inactivation of the enzyme. We conclude that SAM therapy is beneficial in the treatment of lead intoxication.

S-adenosyl-L-methionine and lead intoxication: its therapeutic effect varying the route of administration.

A comparative study on the effect of oral and subcutaneous (sc) or intravenous (iv) administration of S-adenosyl-L-methionine (SAM) in lead poisoning was carried out. SAM was given daily sc (20 mg/kg) and orally (80 mg/kg) to acute lead-intoxicated mice for 20 days. Chronic lead-poisoned patients received SAM, administered intravenously at a daily dose of 12 mg/kg or orally at a dose of 25-30 mg/kg. Independent of the method of administration in either animals or patients, GSH concentration in reduced lead intoxication was increased after SAM dosing. Corresponding blood lead content rapidly decreased and a significant recovery of hepatic and erythrocytic delta-aminolevulinate dehydratase (ALA-D), initially reduced, was clearly produced in the groups receiving SAM, although the response was slightly slower when SAM was given orally. It was found that the bulk of body lead burden was excreted in the feces, showing a peak within the first 24-48 hr and being much greater in animals treated with SAM. In these cases, urinary lead excretion was very low. Lead ALA-D inhibition was also evidenced by elevated urinary excretion of delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and porphyrins. During treatment, precursors and porphyrins elimination declined, reaching normal levels soon after therapy ended. A good correlation between the recovery of both GSH levels and ALA-D activity and decreased lead content was observed.(ABSTRACT TRUNCATED AT 250 WORDS)