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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Publicado: 1986
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01476513_v12_n3_p252_Paredes
http://hdl.handle.net/20.500.12110/paper_01476513_v12_n3_p252_Paredes
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spelling paper:paper_01476513_v12_n3_p252_Paredes2023-06-08T15:12:51Z S-adenosyl-l-methionine and lead intoxication: Its therapeutic effect varying the route of administration 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. 1986 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01476513_v12_n3_p252_Paredes 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
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.
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
publishDate 1986
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01476513_v12_n3_p252_Paredes
http://hdl.handle.net/20.500.12110/paper_01476513_v12_n3_p252_Paredes
_version_ 1768542215362052096