Graphene oxide leads to mitochondrial-dependent apoptosis by activating ROS-p53-mPTP pathway in intestinal cells

Area of Science:

• Biomedical Engineering
• Materials Science
• Toxicology

Background:

• Graphene oxide (GO) possesses unique properties for biomedical applications.
• Biosafety concerns regarding nanomaterials highlight the need for toxicity assessments.
• The impact of GO on small intestinal tissues remains largely uncharacterized.

Purpose of the Study:

• To investigate the toxicological effects of graphene oxide (GO) on intestinal tissues.
• To elucidate the molecular mechanisms underlying GO-induced intestinal cell death.
• To provide a safety reference for the biomedical applications of GO.

Main Methods:

• Characterization of GO nanosheets (size, potential, FT-IR, pro-oxidant properties).
• In vitro cytotoxicity assays on Caco-2 and IEC-6 cell lines.
• In vivo studies using Sprague-Dawley rats with oral GO administration.
• Analysis of oxidative stress markers, apoptosis, and mitochondrial pathways.

Main Results:

• GO exposure induced cytotoxicity in intestinal cell lines by increasing NADPH Oxidase 1 (NOX1) and reactive oxygen species (ROS).
• GO triggered the ROS-CyPD-mPTP signaling pathway, leading to mitochondrial dysfunction and caspase-dependent apoptosis.
• In vivo studies confirmed small intestinal damage, increased apoptosis, and elevated oxidative markers in GO-treated rats.

Conclusions:

• Oral exposure to GO primarily affects the digestive tract, causing intestinal toxicity.
• The ROS-mitochondrial homeostasis-apoptosis axis is crucial in GO-induced intestinal damage.
• Findings underscore the importance of GO's intestinal toxicity for its safe biomedical use.