Novel insights into DEHP-induced zebrafish spleen damage: Cellular apoptosis, mitochondrial dysfunction, and innate immunity.

DEHP (Di(2-ethylhexyl) phthalate) is the most abundant phthalate component detected in environmental samples as it is widely used in the manufacturing of children's toys, medical devices and furniture. Due to its wide prevalence and propensity to accumulate in the food chain, significant concerns have risen about the safety profile of DEHP. Here, we used a zebrafish model to investigate the toxicity mechanisms of DEHP. Our results indicated that exposure to DEHP altered the ROS content in zebrafish spleen and inhibited the activities of antioxidant enzymes SOD and CAT, detoxification enzyme GSH-Px and induced histopathological damage. In addition, elucidated the mechanism of DEHP significantly promoted apoptosis and caused damage in spleen cells through the bax/bcl-2 pathway. Further genetic testing demonstrated significant alterations in mitochondrial biogenesis, fission, and fusion-related genes and suggested potential mechanistic pathways, including GM10532/m6A/FIS1 axis, the STAT3/POA1 axis, and the NFR1/TFAM axis. Serological and genomic analysis indicated that DEHP exposure activated the C3 complement cascade immune pathway and interfered with innate immune function. IBRv2 analysis proposes that innate immunity may serve as a signal indicator of early toxic responses to DEHP pollutants. This study provided comprehensive cellular and genetic data for DEHP toxicity studies and emphasized the need for future management and remediation of DEHP contamination. It also provides data to specifically support the health risk assessments of DEHP, as well as contributing to broader health and environmental research.

Tissue-specific accumulation of DEHP and involvement of endogenous arachidonic acid in DEHP-induced spleen information and injury.

The plasticizer Diethylhexyl phthalate (DEHP), one of the most common contaminants, is widely detected in environmental and biological samples. However, the accumulation of DEHP in tissue and the molecular mechanisms underlying its physiological damage in the spleen of aquatic organisms have not yet been reported. In this study, gas chromatography-mass spectrometry (GC-MS), histology and multi-omics analysis were used to investigate DEHP exposure-induced alterations in transcriptomic profiles and metabolic network of zebrafish model. After exposure to DEHP, higher concentrations of DEHP were found in the intestine, liver and spleen. Anatomical and histological analyses showed that the zebrafish spleen index was significantly increased and inflammatory damage was observed. Increased splenic neutrophil counts indicate inflammation and tissue damage. Transcriptomic filtering showed that 3579 genes were significantly altered. Metabolomic analysis detected 543 differential metabolites. Multi-omics annotation results indicated that arachidonic acid and 12-Hydroperoxyicosatetraenoic acid (HPETE) are involved in the key inflammatory pathway "Inflammatory mediator regulation of TRP channels". This study demonstrated the accumulation characteristics of DEHP in aquatic zebrafish and the mechanisms of inflammation and tissue damage in the spleen which involve endogenous arachidonic acid. This will provide theoretical basis and data support for health risk assessments and tissue damage of DEHP.

Diet-induced iron deficiency in rats impacts small intestinal calcium and phosphate absorption.

AIMS: Recent reports suggest that iron deficiency impacts both intestinal calcium and phosphate absorption, although the exact transport pathways and intestinal segment responsible have not been determined. Therefore, we aimed to systematically investigate the impact of iron deficiency on the cellular mechanisms of transcellular and paracellular calcium and phosphate transport in different regions of the rat small intestine. METHODS: Adult, male Sprague-Dawley rats were maintained on a control or iron-deficient diet for 2 weeks and changes in intestinal calcium and phosphate uptake were determined using the in situ intestinal loop technique. The circulating levels of the hormonal regulators of calcium and phosphate were determined by ELISA, while the expression of transcellular calcium and phosphate transporters, and intestinal claudins were determined using qPCR and western blotting. RESULTS: Diet-induced iron deficiency significantly increased calcium absorption in the duodenum but had no impact in the jejunum and ileum. In contrast, phosphate absorption was significantly inhibited in the duodenum and to a lesser extent the jejunum, but remained unchanged in the ileum. The changes in duodenal calcium and phosphate absorption in the iron-deficient animals were associated with increased claudin 2 and 3 mRNA and protein levels, while levels of parathyroid hormone, fibroblast growth factor-23 and 1,25-dihydroxy vitamin D3 were unchanged. CONCLUSION: We propose that iron deficiency alters calcium and phosphate transport in the duodenum. This occurs via changes to the paracellular pathway, whereby upregulation of claudin 2 increases calcium absorption and upregulation of claudin 3 inhibits phosphate absorption.