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Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat
Heavy metals have a deleterious effect on lower urinary tract functions. Scant data has been reported about metals’ effect on altering detrusor muscle contractility. Rats were given lead acetate (3, 30 mg/kg), cadmium sulfate (0.1, 1 mg/kg) or ferrous sulfate-iron overload-(3, 30 mg/kg), in a subacu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051969/ https://www.ncbi.nlm.nih.gov/pubmed/35498220 http://dx.doi.org/10.1016/j.jsps.2022.01.012 |
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author | Taha, Safaa S. Daabees, Tahia T. Aly, Rania G. Senbel, Amira M. |
author_facet | Taha, Safaa S. Daabees, Tahia T. Aly, Rania G. Senbel, Amira M. |
author_sort | Taha, Safaa S. |
collection | PubMed |
description | Heavy metals have a deleterious effect on lower urinary tract functions. Scant data has been reported about metals’ effect on altering detrusor muscle contractility. Rats were given lead acetate (3, 30 mg/kg), cadmium sulfate (0.1, 1 mg/kg) or ferrous sulfate-iron overload-(3, 30 mg/kg), in a subacute toxicity study (21 days, ip). In-vitro tension experiments were conducted using isolated rat detrusor muscle. Measurement of heavy metal concentrations in blood and tissue homogenates was performed, as well as histopathological examinations. Subacute toxicity induced by treatment with lead and cadmium was manifested as a decrease in EFS, ACh, and ATP-mediated contraction of isolated detrusor muscle. Iron overload only decreased E(MAX) of EFS and ACh-mediated contraction. Lead (30 mg/kg) caused an upward shift in the dose response curve of isoprenaline-induced relaxation, with a significant decrease in E(MAX). Lead (30 mg/kg) or cadmium (1 mg/kg) inhibited adenosine (10(−5) M)-induced relaxation. Comparisons to control tissues showed a selective accumulation of metals in the detrusor muscle. Histopathological examinations revealed edema and inflammation in the urinary bladder. Directly added lead (10 mM) inhibited detrusor muscle contraction in-vitro, and its effect was decreased in presence of atropine, and potentiated in presence of TEA, L-NAME, or MB. Cadmium's (0.1 mM) inhibitory effect was reduced in presence of nifedipine or trifluoperazine. In conclusion, lead, cadmium, or iron induce detrusor hypoactivity: The inhibitory effect of lead may be mediated by modulating muscarinic receptors but not the K(+)/NO/cGMP pathway, whereas cadmium inhibitory effect may be mediated by inhibiting the Ca(2+)/calmodulin pathway. |
format | Online Article Text |
id | pubmed-9051969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-90519692022-04-30 Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat Taha, Safaa S. Daabees, Tahia T. Aly, Rania G. Senbel, Amira M. Saudi Pharm J Original Article Heavy metals have a deleterious effect on lower urinary tract functions. Scant data has been reported about metals’ effect on altering detrusor muscle contractility. Rats were given lead acetate (3, 30 mg/kg), cadmium sulfate (0.1, 1 mg/kg) or ferrous sulfate-iron overload-(3, 30 mg/kg), in a subacute toxicity study (21 days, ip). In-vitro tension experiments were conducted using isolated rat detrusor muscle. Measurement of heavy metal concentrations in blood and tissue homogenates was performed, as well as histopathological examinations. Subacute toxicity induced by treatment with lead and cadmium was manifested as a decrease in EFS, ACh, and ATP-mediated contraction of isolated detrusor muscle. Iron overload only decreased E(MAX) of EFS and ACh-mediated contraction. Lead (30 mg/kg) caused an upward shift in the dose response curve of isoprenaline-induced relaxation, with a significant decrease in E(MAX). Lead (30 mg/kg) or cadmium (1 mg/kg) inhibited adenosine (10(−5) M)-induced relaxation. Comparisons to control tissues showed a selective accumulation of metals in the detrusor muscle. Histopathological examinations revealed edema and inflammation in the urinary bladder. Directly added lead (10 mM) inhibited detrusor muscle contraction in-vitro, and its effect was decreased in presence of atropine, and potentiated in presence of TEA, L-NAME, or MB. Cadmium's (0.1 mM) inhibitory effect was reduced in presence of nifedipine or trifluoperazine. In conclusion, lead, cadmium, or iron induce detrusor hypoactivity: The inhibitory effect of lead may be mediated by modulating muscarinic receptors but not the K(+)/NO/cGMP pathway, whereas cadmium inhibitory effect may be mediated by inhibiting the Ca(2+)/calmodulin pathway. Elsevier 2022-03 2022-01-24 /pmc/articles/PMC9051969/ /pubmed/35498220 http://dx.doi.org/10.1016/j.jsps.2022.01.012 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Taha, Safaa S. Daabees, Tahia T. Aly, Rania G. Senbel, Amira M. Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
title | Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
title_full | Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
title_fullStr | Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
title_full_unstemmed | Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
title_short | Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
title_sort | lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051969/ https://www.ncbi.nlm.nih.gov/pubmed/35498220 http://dx.doi.org/10.1016/j.jsps.2022.01.012 |
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