Abstract:
:Drug-induced phospholipidosis (DIPL) is characterized by phospholipid storage in the lysosomes of affected tissues. Many severe effects and toxicities have been linked to DIPL. The aim of this study was to determine whether the endogenous opioid system is involved in chloroquine-induced phospholipidosis. The effect of naltrexone as an antagonist of opioid receptors in chloroquine-induced phospholipidosis in rat liver was investigated by morphological, biochemical, and molecular modelling studies. Transmission electron microscopy (TEM) showed that morphological characteristic changes of rat liver, including the number of lamellar bodies, grade of vacuolization and cell steatosis, were markedly attenuated in rats treated with naltrexone alone or in combination with chloroquine, in comparison with chloroquine-treated rats. The results of liquid chromatography mass spectrometry (LC/MS) showed that the concentrations of phenylacetylglycine (PAG) and hippuric acid (HA) were significantly decreased and increased, respectively, in target groups. Besides, the concentration ratio of PAG/HA was significantly decreased. Spectrophotometry resulted in a notable decrease in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in target groups. The results from the molecular docking and molecular dynamic simulation studies demonstrated clear chloroquine interaction with the active site cavity of the µ opioid receptor. These data suggest that administration of naltrexone alone, or in combination with chloroquine, notably attenuates the side effects of chloroquine-induced phospholipidosis, as well as demonstrating an increased probability of the endogenous opioid system involvement in chloroquine-induced phospholipidosis in rat liver.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Malek MR,Ahmadian S,Dehpour AR,Ebrahim-Habibi A,Shafizadeh M,Kashani-Amin Edoi
10.1111/1440-1681.13332subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1575-1583issue
9eissn
0305-1870issn
1440-1681journal_volume
47pub_type
杂志文章abstract::1. The present review describes the actions of sensory neuropeptides on the contractility of the rat and guinea-pig prostate gland and discusses the differences in sensitivity of the smooth muscle of the prostates taken from these species to these neuropeptides. 2. Nerve fibres immunoreactive for the tachykinins subst...
journal_title:Clinical and experimental pharmacology & physiology
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journal_title:Clinical and experimental pharmacology & physiology
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doi:10.1111/j.1440-1681.1977.tb02675.x
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doi:10.1111/1440-1681.12818
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journal_title:Clinical and experimental pharmacology & physiology
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1976.tb00620.x
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pub_type: 杂志文章
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journal_title:Clinical and experimental pharmacology & physiology
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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更新日期:1998-10-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
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doi:10.1111/j.1440-1681.1978.tb00708.x
更新日期:1978-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00358.x
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更新日期:2004-10-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2005.04168.x
更新日期:2005-03-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
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更新日期:1989-06-01 00:00:00
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更新日期:2020-04-01 00:00:00
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更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2008-09-01 00:00:00
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更新日期:2019-10-01 00:00:00
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doi:10.1111/j.1440-1681.1996.tb02765.x
更新日期:1996-06-01 00:00:00
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更新日期:2011-01-01 00:00:00