Related Experiment Video

Updated: Dec 25, 2025

Laser Ablation of the Zebrafish Pronephros to Study Renal Epithelial Regeneration
07:27

Laser Ablation of the Zebrafish Pronephros to Study Renal Epithelial Regeneration

Published on: August 29, 2011

15.6K

Androgen/androgen receptor affects gentamicin-induced nephrotoxicity through regulation of megalin expression

Elsayed G E Elsakka1, Ahmad Mohamed Elsisi2, Osama Abd Al-Motaal Mansour1

  • 1Biochemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.

Life Sciences
|April 6, 2020
PubMed
Abstract

Insights

Androgens regulate megalin expression and function, impacting gentamicin-induced nephrotoxicity (GIN). Targeting the androgen receptor (AR) may offer new strategies for GIN prevention and treatment, potentially explaining sex differences in kidney injury.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Gentamicin-induced nephrotoxicity (GIN) is a significant clinical concern.
  • The role of androgens and their receptor (AR) in GIN is not fully understood.
  • Megalin, a receptor implicated in proximal tubule function and drug uptake, is a potential mediator.

Purpose of the Study:

  • To investigate the influence of androgen/AR signaling on megalin expression and function.
  • To determine the effect of this regulation on gentamicin-induced nephrotoxicity.
  • To explore potential therapeutic targets for GIN.

Main Methods:

  • Male Wistar rats were treated with gentamicin and/or AR ligands (testosterone or flutamide).
  • Megalin expression (mRNA, protein) and function (FITC-BSA uptake) were assessed.
  • Kidney injury was evaluated via histopathology, blood urea nitrogen (BUN), serum creatinine (SCr), albumin/creatinine ratio (A/C), and neutrophil gelatinase-associated lipocalin (NGAL) expression.

Main Results:

  • Testosterone administration increased megalin expression and function, exacerbating GIN.
  • Flutamide treatment ameliorated GIN and reduced megalin expression/function.
  • Computational analysis identified androgen response elements in the megalin promoter.

Conclusions:

  • Androgen/AR signaling transcriptionally regulates megalin expression.
  • This regulation directly impacts the severity of gentamicin-induced nephrotoxicity.
  • The androgen/AR-megalin axis represents a potential therapeutic target for GIN, possibly explaining sexual dimorphism in kidney injury.
Keywords:
Androgen receptorFlutamideGentamicinMegalinNephrotoxicityTestosterone

More Related Videos

Kidney Regeneration in Adult Zebrafish by Gentamicin Induced Injury06:25

Kidney Regeneration in Adult Zebrafish by Gentamicin Induced Injury

Published on: August 3, 2015

11.2K
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

855

Related Concept Videos

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
169
Estimation of k and VD of Aminoglycosides01:20

Estimation of k and VD of Aminoglycosides

Aminoglycosides are a class of antibiotics used to treat various bacterial infections. Clinicians must determine the elimination rate constant (k) and volume of distribution (VD) to optimize therapeutic efficacy and minimize toxicity. The k value represents the rate at which the drug is removed from the body, and the VD reflects the degree to which the drug distributes into body tissues. Accurately estimating these parameters allows healthcare professionals to tailor drug dosing to individual...
144
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion01:18

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion

In geriatric patients, renal physiology undergoes significant changes, including diminished renal blood flow and a lower glomerular filtration rate (GFR), leading to alterations in medication clearance. Drugs such as aminoglycoside antibiotics, lithium, and digoxin, which rely on glomerular filtration for removal from the body, particularly impact pharmacokinetics. These drugs tend to have slower clearance rates in older adults, necessitating careful dosage considerations.Evaluation of renal...
185
Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
3.2K
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
165
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K