The effect of aryl hydrocarbon receptor ligands on gentamicin-induced nephrotoxicity in rats

Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs,...

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Bibliographic Details
Published in:Environmental science and pollution research international 2020-05, Vol.27 (14), p.16189-16202
Main Authors: Mokhtar, Mahmoud Mohamed, Khidr, Emad Gamil, Shaban, Hesham Mohamed, Allam, Shady, Elsadek, Bakheet E. M., Salama, Salama Abdou, Ali, Shawkey Saddik
Format: Article
Language:English
Subjects:
Albumins
Aminoglycosides
Aquatic Pollution
Aromatic compounds
Atmospheric Protection/Air Quality Control/Air Pollution
Benzo(a)pyrene
Creatinine
Earth and Environmental Science
Ecotoxicology
Environment
Environmental Chemistry
Environmental Health
Environmental science
Gene expression
Genes
Gentamicin
Hydrocarbons
Kidneys
Ligands
Localization
Polycyclic aromatic hydrocarbons
Proximal tubules
Pyrene
Receptors
Research Article
Resveratrol
Waste Water Technology
Water Management
Water Pollution Control
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Summary:Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs, including aminoglycosides. In the current study, we investigated the expression and localization of AhR and megalin in rat kidney. Furthermore, we investigated whether AhR and its ligands could modulate the expression of megalin and consequently the gentamicin-induced nephrotoxicity (GN) in rats. Both megalin and AhR receptors are expressed in the proximal tubules of the rat kidney. Treatment with AhR agonist benzo( a )pyrene aggravated GN as indicated by a significant increase in serum creatinine, BUN, KIM1, NAGL, CD-86, and urinary albumin/creatinine ratio. On the other hand, treatment with AhR antagonist resveratrol ameliorated GN as manifested by a pronounced decrease in the aforementioned parameters. The effects of AhR ligands on GN were associated with altered expression of megalin receptor.
ISSN:0944-1344
1614-7499
DOI:10.1007/s11356-020-08073-z