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

被引：9

作者：

Mokhtar, Mahmoud Mohamed ^{[1
]}

Khidr, Emad Gamil ^{[1
]}

Shaban, Hesham Mohamed ^{[1
]}

Allam, Shady ^{[2
]}

Elsadek, Bakheet E. M. ^{[3
]}

Salama, Salama Abdou ^{[4
]}

Ali, Shawkey Saddik ^{[1
]}

机构：

[1] Al Azhar Univ, Fac Pharm Boys, Dept Biochem, Almokhayam Aldaem St,6th Prov, Cairo 13465, Egypt

[2] Kafrelsheikh Univ, Fac Pharm, Dept Pharmacol & Toxicol, Kafr Al Sheikh, Egypt

[3] Al Azhar Univ, Assuit Branch, Fac Pharm Boys, Dept Biochem, Assiut, Egypt

[4] Al Azhar Univ, Fac Pharm Boys, Dept Pharmacol & Toxicol, Almokhayam Aldaem St,6th Prov, Cairo 13465, Egypt

来源：

ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH | 2020年 / 27卷 / 14期

关键词：

AhR; Megalin; Gentamicin; Benzo(a)pyrene; Resveratrol; PAHS; Nephrotoxicity; THERAPEUTIC APPROACH; UP-REGULATION; DNA-DAMAGE; TNF-ALPHA; EXPRESSION; MEGALIN; RESVERATROL; ANTAGONIST; APOPTOSIS; PROTEINS;

D O I：

10.1007/s11356-020-08073-z

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

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.

引用

页码：16189 / 16202

页数：14