Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Neurological impairment is crucial for tire rubber-derived contaminant 6PPDQ-induced acute toxicity to rainbow trout.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ) has attracted significant attention due to its highly acute lethality to sensitive salmonids. However, studies investigating the mechanisms underlying its acute toxicity have been lacking. In this work, we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality. Moribund trout exhibited significantly higher brain concentrations of 6PPDQ compared to surviving trout. In an in vitro model using human brain microvascular endothelial cells, 6PPDQ can penetrate the blood-brain barrier and enhance blood-brain barrier permeability without compromising cell viability. The time spent in the top of the tank increased with rising 6PPDQ concentrations, as indicated by locomotion behavior tests. Furthermore, 6PPDQ influenced neurotransmitter levels and mRNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations. The integrated biomarker response value associated with neurotoxicity showed a positive linear correlation with trout mortality. These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes, including behavioral effects and mortality, induced by 6PPDQ.

[Dissolution determination of Shuanghuanglian capsules by HPLC analysis assisted with principal component analysis].

OBJECTIVE: To develop a quality analysis method based on self-reference principal for dissolution determination of Shuanghuanglian capsules. METHOD: Dissolution of Shuanghuanglian capsules was determined by principal component analysis consociated HPLC method. RESULT: The liner of regression equation was good. The average recovery rates of quality assurance samples (QA) and quality control samples (QC) were all no less than 96. 0%. Dissolution curves of Shuanghuanlian capsules of different manufacturers and different batches of the same manufacturer had obvious disparity. CONCLUSION: The method can better evaluate the dissolution conditions of Shuanghuanglian capsules. The prospect of the method is expected for assessing the dissolution of other oral solid dosage of traditional Chinese medicines.

Identifying potential toxic organic substances in leachates from tire wear particles and their mechanisms of toxicity to Scenedesmus obliquus.

Tire wear particles (TWPs) are increasingly being found in the aquatic environment. However, there is limited information available on the environmental consequences of TWP constituents that may be release into water. In this study, TWP leachate samples were obtained by immersing TWPs in ultrapure water. Using high-resolution mass spectrometry and toxicity identification, we identified potentially toxic organic substances in the TWP leachates. Additionally, we investigated their toxicity and underlying mechanisms. Through our established workflow, we structurally identified 13 substances using reference standards. The median effective concentration (EC50) of TWP leachates on Scenedesmus obliquus growth was comparable to that of simulated TWP leachates prepared with consistent concentrations of the 13 identified substances, indicating their dominance in the toxicity of TWP leachates. Among these substances, cyclic amines (EC50: 1.04-3.65 mg/L) were found to be toxic to S. obliquus. We observed significant differential metabolites in TWP leachate-exposed S. obliquus, primarily associated with linoleic acid metabolism and purine metabolism. Oxidative stress was identified as a crucial factor in algal growth inhibition. Our findings shed light on the risk posed by TWP leachable substances to aquatic organisms.