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Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Liver Physiology01:30

Liver Physiology

The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of  70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can also...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

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, mediated...

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Related Experiment Video

Updated: Jun 24, 2026

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

Systems biology for identifying liver toxicity pathways.

Zheng Li1, Christina Chan

  • 1Cellular and Molecular Biology Lab, Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA. lizheng1@gmail.com

BMC Proceedings
|March 13, 2009
PubMed
Summary

Drug-induced liver toxicity is a major cause of acute liver failure. This study used systems biology to identify pathways and gene targets involved in liver toxicity from free fatty acids and tumor necrosis factor-alpha.

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An All-Human Hepatic Culture System for Drug Development Applications
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An All-Human Hepatic Culture System for Drug Development Applications

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Last Updated: Jun 24, 2026

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

An All-Human Hepatic Culture System for Drug Development Applications
07:23

An All-Human Hepatic Culture System for Drug Development Applications

Published on: October 20, 2023

Area of Science:

  • Biochemistry
  • Cell Biology
  • Toxicology

Background:

  • Drug-induced liver toxicity is a leading cause of acute liver failure in the US.
  • Identifying specific molecular pathways is crucial for understanding and mitigating liver damage.

Purpose of the Study:

  • To describe systems biology methods for identifying pathways in liver toxicity.
  • To investigate toxicity induced by free fatty acids (FFA) and tumor necrosis factor (TNF)-alpha in HepG2/C3A cells.

Main Methods:

  • Developed systems biology approaches to integrate multi-level data.
  • Integrated gene expression, metabolite profiles, toxicity measurements, and prior knowledge.
  • Used computational prediction and experimental validation to identify gene targets.

Main Results:

  • Identified key pathways involved in FFA- and TNF-alpha-induced liver toxicity.
  • Computationally predicted gene targets that modulate liver toxicity.
  • Experimentally validated some of the predicted gene targets.

Conclusions:

  • Systems biology offers a powerful approach to dissect complex mechanisms of drug-induced liver toxicity.
  • Identified potential gene targets for therapeutic intervention against liver toxicity.