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 re...
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todo:paper_01476513_v12_n3_p252_Paredes2023-10-03T15:00:38Z S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration Paredes, S.R. Fukuda, H. Kozicki, P.A. Rossetti, M.V. Conti, H. Batlle, A.M.d.C. lead s adenosylmethionine animal experiment drug administration human intoxication intravenous drug administration mouse oral drug administration subcutaneous drug administration Animals Body Burden Glutathione Lead Lead Poisoning Liver Male Mice Porphobilinogen Synthase S-Adenosylmethionine Animalia 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 δ-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 δ-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. This supports our proposal that as a result of SAM dosing, GSH availability is increased, facilitating the detoxification process by rapid removal of lead from different compartments and consequently reversing lead inactivation of the enzyme. Liver would then play an important role in the uptake and transport of lead as a glutathione conjugate to bile, giving rise to a greater biliary metal excretion and avoiding the known risks produced by chelation therapy, which could eventually result in renal failure. © 1986. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01476513_v12_n3_p252_Paredes |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
lead s adenosylmethionine animal experiment drug administration human intoxication intravenous drug administration mouse oral drug administration subcutaneous drug administration Animals Body Burden Glutathione Lead Lead Poisoning Liver Male Mice Porphobilinogen Synthase S-Adenosylmethionine Animalia |
| spellingShingle |
lead s adenosylmethionine animal experiment drug administration human intoxication intravenous drug administration mouse oral drug administration subcutaneous drug administration Animals Body Burden Glutathione Lead Lead Poisoning Liver Male Mice Porphobilinogen Synthase S-Adenosylmethionine Animalia Paredes, S.R. Fukuda, H. Kozicki, P.A. Rossetti, M.V. Conti, H. Batlle, A.M.d.C. S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration |
| topic_facet |
lead s adenosylmethionine animal experiment drug administration human intoxication intravenous drug administration mouse oral drug administration subcutaneous drug administration Animals Body Burden Glutathione Lead Lead Poisoning Liver Male Mice Porphobilinogen Synthase S-Adenosylmethionine Animalia |
| description |
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 δ-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 δ-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. This supports our proposal that as a result of SAM dosing, GSH availability is increased, facilitating the detoxification process by rapid removal of lead from different compartments and consequently reversing lead inactivation of the enzyme. Liver would then play an important role in the uptake and transport of lead as a glutathione conjugate to bile, giving rise to a greater biliary metal excretion and avoiding the known risks produced by chelation therapy, which could eventually result in renal failure. © 1986. |
| format |
JOUR |
| author |
Paredes, S.R. Fukuda, H. Kozicki, P.A. Rossetti, M.V. Conti, H. Batlle, A.M.d.C. |
| author_facet |
Paredes, S.R. Fukuda, H. Kozicki, P.A. Rossetti, M.V. Conti, H. Batlle, A.M.d.C. |
| author_sort |
Paredes, S.R. |
| title |
S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration |
| title_short |
S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration |
| title_full |
S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration |
| title_fullStr |
S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration |
| title_full_unstemmed |
S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration |
| title_sort |
s-adenosyl-l-methionine and lead intoxication: its therapeutic effect varying the route of administration |
| url |
http://hdl.handle.net/20.500.12110/paper_01476513_v12_n3_p252_Paredes |
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