Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Pharmacokinetic Models: Overview01:20

Pharmacokinetic Models: Overview

1.7K
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
1.7K
Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

637
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
637
Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

153
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
153
Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

253
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
253
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

183
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
183
Mechanistic Models: Overview of Compartment Models01:21

Mechanistic Models: Overview of Compartment Models

277
Mechanistic models, a category encompassing both physiological and compartmental modeling, differ from empirical models' approaches to incorporating known factors about the systems being modeled. Empirical models describe data with minimal assumptions, while mechanistic models aim to provide a robust description of available data by specifying assumptions and integrating known factors about the system. Compartmental analysis is a key example of a mechanistic model in pharmacokinetics and...
277

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Safety Assessment of Radish Root - Derived Ingredients as Used in Cosmetics.

International journal of toxicology·2026
Same author

Proteomic profiling of drug and nutrient transporter expression by small intestinal region in neonates, pediatrics, and adults.

bioRxiv : the preprint server for biology·2026
Same author

Amended Safety Assessment of Naturally-Sourced Clays as Used in Cosmetics.

International journal of toxicology·2026
Same author

Safety Assessment of Diatomaceous Earth as Used in Cosmetics.

International journal of toxicology·2026
Same author

Safety Assessment of Basic Yellow 87 as Used in Cosmetics.

International journal of toxicology·2026
Same author

Safety Assessment of Glycolactones as Used in Cosmetics.

International journal of toxicology·2026

Related Experiment Video

Updated: Dec 9, 2025

Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury
07:58

Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury

Published on: July 17, 2016

9.1K

Microphysiological system modeling of ochratoxin A-associated nephrotoxicity.

Tomoki Imaoka1, Jade Yang1, Lu Wang2

  • 1Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, 98195, USA.

Toxicology
|September 9, 2020
PubMed
Summary

Ochratoxin A (OTA) causes kidney damage. A 3D kidney model revealed OTA is detoxified by glutathione S-transferases (GSTs) and bioactivated by P450 enzymes, impacting NRF2-regulated genes and kidney function.

Keywords:
GSTsMicrophysiological systemsNephrotoxicityOchratoxin AOxidative stressProximal tubule epithelial cells

More Related Videos

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.1K
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
07:52

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Published on: November 7, 2017

21.6K

Related Experiment Videos

Last Updated: Dec 9, 2025

Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury
07:58

Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury

Published on: July 17, 2016

9.1K
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.1K
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
07:52

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Published on: November 7, 2017

21.6K

Area of Science:

  • Toxicology
  • Nephrology
  • Biochemistry

Background:

  • Ochratoxin A (OTA) is a prevalent food contaminant with known carcinogenic, nephrotoxic, teratogenic, and immunotoxic effects.
  • Severe nephrotoxicity, marked by proximal tubule degeneration and fibrosis, is a primary concern, yet human kidney toxicity mechanisms and genetic risk factors remain unclear due to inadequate in vitro models.
  • A 3D human kidney proximal tubule microphysiological system (kidney MPS) offers a promising model to study OTA's renal effects.

Purpose of the Study:

  • To evaluate dose-response relationships of OTA in a kidney MPS.
  • To identify the role of active transport proteins in OTA's renal disposition.
  • To determine the contribution of metabolism (bioactivation and detoxification) to OTA toxicity using the kidney MPS.

Main Methods:

  • Utilized a 3D human kidney proximal tubule microphysiological system (kidney MPS) to model OTA exposure.
  • Assessed OTA toxicity using LIVE/DEAD staining and measured kidney injury biomarkers in the MPS effluent.
  • Investigated the roles of P450 and glutathione S-transferase (GST) enzymes using specific inhibitors (ABT and NBDHEX).
  • Performed RNA-sequencing to analyze transcriptional changes in response to OTA.
  • Conducted OTA transport studies in the presence and absence of probenecid.

Main Results:

  • OTA exhibited dose-dependent toxicity in the kidney MPS, with LC50 values aligning with clinical urinary concentrations.
  • Kidney injury biomarkers unexpectedly decreased with increasing OTA concentration.
  • Inhibition of GSTs (NBDHEX) enhanced OTA toxicity, while P450 inhibition (ABT) decreased it, indicating GSTs detoxify and P450s bioactivate OTA.
  • RNA-sequencing revealed OTA downregulates NRF2-regulated genes, including GSTs, suggesting impaired detoxification contributes to toxicity.
  • Probenecid studies indicated involvement of organic anion transporters in OTA's kidney disposition.

Conclusions:

  • The kidney MPS effectively models OTA nephrotoxicity, revealing complex dose-response relationships and biomarker behavior.
  • Glutathione S-transferases (GSTs) play a crucial role in OTA detoxification, while P450 enzymes contribute to its bioactivation.
  • Downregulation of NRF2-regulated genes, particularly GSTs, is a key mechanism in OTA-induced kidney injury.
  • Findings support improved risk assessment and regulatory policies for OTA exposure, and highlight the potential role of genetic factors in susceptibility to OTA nephrotoxicity.