p‐Cresol and p‐Cresyl Sulphate Boost Oxidative Stress: A Systematic Review of Recent Evidence
PMCID: PMC12177445
PMID: 40534235
DOI: 10.1111/bcpt.70065
Journal: Basic & clinical pharmacology & toxicology
Publication Date: 2025-6-18
Authors: Renaldi R, Wiguna T, Persico AM, Tanra AJ
Key Points
- p-Cresol and PCS induce oxidative stress through NADPH oxidase activation, with potential implications for neurological and metabolic disorders
- Concentrations as low as 100 μM can decrease glutathione content by up to 47% and increase ROS production
- Antioxidant pre-treatment (NAC, ascorbate, α-tocopherol) shows promise in mitigating p-cresol-induced oxidative damage
Summary
This systematic review explores the role of p-cresol and p-cresyl sulphate (PCS) in inducing oxidative stress across various pathological conditions, including chronic kidney disease (CKD), neurodegenerative disorders, and autism spectrum disorder (ASD). By analyzing six studies spanning in vitro and animal models, the research reveals critical mechanisms by which these uremic toxins contribute to cellular dysfunction through reactive oxygen species (ROS) generation and inflammatory processes.
The review demonstrates that p-cresol and PCS can trigger oxidative stress through multiple pathways, including NADPH oxidase activation, disruption of neurotrophic factor signaling, and modulation of neurotransmitter systems. At concentrations commonly observed in CKD patients (100 μM), these compounds can induce significant cellular changes, including glutathione depletion, increased inflammatory markers, and potential neurological impairments, without necessarily causing direct cell death.