Disruption of Mitochondrial Bioenergetics Links Oxidative Stress-Mediated Apoptosis to Hepatorenal Injury Following Sub-Chronic Exposure to Titanium Dioxide Nanoparticles.
- 1Laboratory of Toxicology and Ecosystems Pathologies, Department of Living Beings, Echahid Cheikh Larbi Tebessi University, Tebessa 12002, Algeria.
- 2Laboratory of Toxicology and Ecosystems Pathologies, Department of Applied Biology, Echahid Cheikh Larbi Tebessi University, Tebessa 12002, Algeria.
- 3Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
Abstract
Titanium dioxide nanoparticles (TiO₂-NPs) are widely used nanomaterials, but their potential systemic toxicity following chronic exposure remains a significant concern. This study investigated whether mitochondrial dysfunction represents a key mechanistic link between oxidative stress, apoptosis, and organ injury induced by TiO₂-NPs. Male Wistar rats were orally exposed for 90 days to TiO₂-NPs (15-31 nm) at doses of 215 or 500 mg/kg body weight. Mitochondrial analyses revealed significantly impaired respiratory activity, increased membrane permeability, and mitochondrial swelling, indicating disruption of mitochondrial function and electron transport chain integrity. These alterations were accompanied by increased reactive oxygen species production; depletion of antioxidant defenses, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and glutathione S-transferase (GST); and enhanced lipid peroxidation. Increased caspase-3 activation further suggested the involvement of mitochondria-dependent apoptotic pathways. Histopathological examination confirmed significant hepatorenal damage, including hepatocellular degeneration, inflammatory infiltration, vascular alterations, and glomerular and tubular lesions. Overall, integrating mitochondrial, oxidative, apoptotic, and histopathological findings supports a mechanistic model in which mitochondrial bioenergetic dysfunction acts as a central event linking oxidative imbalance to apoptosis and tissue injury. These findings contribute to a better understanding of TiO₂-NP-associated health risks and provide mechanistic insights relevant to the safer development and application of nanomaterials.
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BibTeX
@article{bouzenzana2026disruption,
title = {{Disruption of Mitochondrial Bioenergetics Links Oxidative Stress-Mediated Apoptosis to Hepatorenal Injury Following Sub-Chronic Exposure to Titanium Dioxide Nanoparticles.}},
author = {Sara Bouzenzana and Rachid Rouabhi and Rosa Carotenuto and Chiara Fogliano and Simona Di Marino and Bice Avallone and Chiara Maria Motta},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198653},
url = {https://europepmc.org/article/MED/42883901},
note = {CC BY},
}
RIS
TY - JOUR
TI - Disruption of Mitochondrial Bioenergetics Links Oxidative Stress-Mediated Apoptosis to Hepatorenal Injury Following Sub-Chronic Exposure to Titanium Dioxide Nanoparticles.
AU - Sara Bouzenzana
AU - Rachid Rouabhi
AU - Rosa Carotenuto
AU - Chiara Fogliano
AU - Simona Di Marino
AU - Bice Avallone
AU - Chiara Maria Motta
PY - 2026
DA - 2026/09/28
JO - International journal of molecular sciences
DO - 10.3390/ijms27198653
UR - https://europepmc.org/article/MED/42883901
AB - Titanium dioxide nanoparticles (TiO₂-NPs) are widely used nanomaterials, but their potential systemic toxicity following chronic exposure remains a significant concern. This study investigated whether mitochondrial dysfunction represents a key mechanistic link between oxidative stress, apoptosis, and organ injury induced by TiO₂-NPs. Male Wistar rats were orally exposed for 90 days to TiO₂-NPs (15-31 nm) at doses of 215 or 500 mg/kg body weight. Mitochondrial analyses revealed significantly impaired respiratory activity, increased membrane permeability, and mitochondrial swelling, indicating disruption of mitochondrial function and electron transport chain integrity. These alterations were accompanied by increased reactive oxygen species production; depletion of antioxidant defenses, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and glutathione S-transferase (GST); and enhanced lipid peroxidation. Increased caspase-3 activation further suggested the involvement of mitochondria-dependent apoptotic pathways. Histopathological examination confirmed significant hepatorenal damage, including hepatocellular degeneration, inflammatory infiltration, vascular alterations, and glomerular and tubular lesions. Overall, integrating mitochondrial, oxidative, apoptotic, and histopathological findings supports a mechanistic model in which mitochondrial bioenergetic dysfunction acts as a central event linking oxidative imbalance to apoptosis and tissue injury. These findings contribute to a better understanding of TiO₂-NP-associated health risks and provide mechanistic insights relevant to the safer development and application of nanomaterials.
SN - 1422-0067
ER -