Environmental researchOct 7, 2026

Multiple Toxic Effects of 6PPD-Q and Titanium Dioxide Nanoparticles on Mussels' Brain Chemistry, Daily Rhythms, and Metabolism

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 8, 2026

Abstract

Exposure to 6PPD-quinone and titanium dioxide nanoparticles significantly impaired the physiological performance of the thick-shell mussel Mytilus coruscus.

High-concentration co-exposure to 6PPD-Q and TiO₂ NPs led to reduced clearance rates and altered oxygen to nitrogen ratios in mussels.
Increased oxygen consumption and excretion rates were observed, along with pronounced gill histopathological injury.
Energy metabolism disruption was indicated by decreased ATP content and inhibited enzyme activities related to metabolism.
Clear alterations in the expression of genes linked to circadian rhythms and metabolism were noted, suggesting potential disruptions in neuro-circadian-metabolic regulation.
Oxidative stress was evident, indicated by changes in antioxidant enzyme activities and elevated levels of malondialdehyde.
Significant modulation of inflammatory and apoptotic gene expressions was observed, indicating potential immune and cell death responses.

Simplified

Tire-derived 6PPD-quinone (6PPD-Q) and titanium dioxide nanoparticles (TiO₂ NPs) are increasingly detected in aquatic environments, yet their combined effects on marine bivalves remain poorly understood. In this study, the thick-shell mussel Mytilus coruscus was exposed to 6PPD-Q, TiO₂ NPs, and their mixtures to evaluate multi-level physiological, biochemical, histological, and molecular responses. The results demonstrated that 6PPD-Q and TiO₂ NPs, particularly under high-concentration co-exposure, significantly impaired mussel physiological performance, as indicated by reduced clearance rate and O:N ratio, increased oxygen consumption and excretion rate, and pronounced gill histopathological injury. Co-exposure also caused clear energy metabolic disruption, including decreased ATP content and inhibited CS, LDH, and PK activities, together with suppressed neurotransmitter levels of DA, ACh, and GABA. In addition, the expression patterns of circadian rhythm- and metabolism-related genes, including CRY, Per2, PPARγ, ACO, and PEPCK, were markedly altered, suggesting disruption of neuro-circadian-metabolic regulation. Oxidative stress was evident in both gills and digestive gland, as reflected by altered CAT and SOD activities and elevated MDA levels. These responses were accompanied by significant modulation of inflammatory and apoptotic genes, including TNF-α, IL-17, TGF-β, Caspase-3, Caspase-8, and Bcl-2. These findings suggest that 6PPD-Q and TiO₂ NPs may jointly impair mussel health by linking gill first-contact injury with metabolic dysregulation, oxidative stress, and immune-apoptotic damage.

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Multiple Toxic Effects of 6PPD-Q and Titanium Dioxide Nanoparticles on Mussels' Brain Chemistry, Daily Rhythms, and Metabolism

Abstract

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