Paraoxonase 1 and oxidative stress in paediatric non-alcoholic steatohepatitis

Sonal Desai1, Susan S Baker, Wensheng Liu

  • 1Women and Children's Hospital of Buffalo, Department of Pediatrics, the State University of New York, Buffalo, NY, USA.

Insights

Children with non-alcoholic steatohepatitis (NASH) show increased liver expression of catalase and paraoxonase 1 (PON1). These findings suggest potential protective roles for these antioxidants in NASH.

Area of Science:

  • Pediatric Hepatology
  • Oxidative Stress Research
  • Biomarker Discovery

Background:

  • Non-alcoholic steatohepatitis (NASH) in children is a growing health issue.
  • Oxidative stress plays a key role in NASH development.
  • Antioxidant enzymes are crucial for liver protection.

Purpose of the Study:

  • To investigate the expression of antioxidant enzymes in pediatric NASH.
  • To understand the role of these enzymes in NASH pathophysiology.
  • To identify potential therapeutic targets for NASH.

Main Methods:

  • Assessed mRNA expression of catalase, GPX1, GSR, PON1, and ROS-related genes using microarrays and qPCR.
  • Quantified PON1 protein levels in liver and serum via Western blot.
  • Measured serum enzymatic activities of GPX, GSR, and PON1.

Main Results:

  • NASH livers showed higher mRNA expression of catalase and PON1, but not GPX1 or GSR.
  • PON1 mRNA and protein were elevated in NASH livers.
  • No significant differences in serum GPX or GSR activity were found between NASH patients and controls.

Conclusions:

  • Elevated catalase and PON1 expression in NASH livers suggests a protective function.
  • These antioxidant enzymes may represent important therapeutic targets for NASH interventions.
  • Further research into these enzymes could lead to new treatments for pediatric NASH.
Abstract

Related Concept Videos

Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Protein Import into the Peroxisomes01:27

Protein Import into the Peroxisomes

Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
Phase I Oxidative Reactions: Overview01:19

Phase I Oxidative Reactions: Overview

Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...