Revealing the toxicity of dimethyl phthalate (DMP) to the oxygen-carrying function of red blood cells (RBCs): The iron release mechanism

Chi, Zhenxing; Liu, Jia; Tan, Songwen; Lin, Hongwei; Wang, Weilin; Li, Weiguo

doi:10.1016/j.chemosphere.2020.128017

Cited by 21 publications

(5 citation statements)

References 39 publications

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“…Notably, our findings indicated a decline in the counts of RBC, along with a decreased concentration of HGB and MCHC in the coccygeal vein during HS conditions. The HGB is an iron-containing protein complex that transports oxygen throughout the body and is usually found in RBC [ 31 ]. Arterial oxygen concentration and consequently tissue oxygenation are directly affected by HGB levels [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Heat stress affects dairy cow health status through blood oxygen availability

Zeng,

Cai,

Wang

et al. 2023

J Animal Sci Biotechnol

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Background Rises in global warming and extreme weather occurrence make the risk of heat stress (HS) induced by high ambient temperatures more likely in high-yielding dairy cows, resulting in low milk quality and yield. In animals, oxygen is involved in many physiological and metabolic processes, but the effects of HS on oxygen metabolism remain unclear. Thus, the current study aimed to investigate how oxygen metabolism plays a role in health status of dairy cows by measuring the milk yield, milk composition, and blood biochemical variables of cows under different levels of HS: none (No-HS), mild (Mild-HS), and moderate HS (Mod-HS). Results The HS significantly increased rectal temperature (Ptreat < 0.01) and respiration rate (Ptreat < 0.01). Under Mod-HS, greater Na+ (P < 0.05) and lower total CO2, and pH (P < 0.05) were observed relative to those under No-HS and Mild-HS. Oxygen concentrations in both coccygeal artery and mammary vein (Ptreat < 0.01) were lower under Mod-HS than under No-HS. Coccygeal vein concentrations of heat shock protein 90 (HSP90) (P < 0.05) increased during Mod-HS compared with those in cows under No-HS. Malondialdehyde increased during Mod-HS, and glutathione peroxidase (P < 0.01) increased during Mild-HS. Coccygeal vein concentrations of vascular endothelial growth factor (P < 0.01), heme oxygenase-1 (P < 0.01), and hypoxia-inducible factor 1α (P < 0.01) were greater in cows under Mod-HS than those under No-HS. Red blood cell count (P < 0.01) and hemoglobin concentration (P < 0.01) were lower in the coccygeal vein of dairy cows under Mild- and Mod-HS than those of cows under No-HS. Conclusions Exposure to HS negatively impacts the health status and lactation performance of dairy cows by limiting oxygen metabolism and transportation. However, the specific mechanism by which HS affects mammary function in cows remains unclear and requires further exploration.

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Section: Discussionmentioning

confidence: 99%

Heat stress affects dairy cow health status through blood oxygen availability

Zeng,

Cai,

Wang

et al. 2023

J Animal Sci Biotechnol

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“…In this case, the key to detecting the free iron ions is to separate the aqueous phase from the biomacromolecules and organelles in the cytoplasm without affecting the protein-bound iron contents. Based on a previously reported method, 29 we adopted ultrafiltration to obtain the free iron ions-containing filtrates from the cytoplasmic inclusions of DeFer-2-treated B16F10 cells. And the detected iron contents were normalized to the total cellular protein.…”

Section: Defer-2 Rapidly Elevates Intracellular Free Iron Content To ...mentioning

confidence: 99%

Small-Molecule Ferritin Degrader as a Pyroptosis Inducer

Chen

Kwon

et al. 2023

J. Am. Chem. Soc.

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Exploring the response of malignant cells to intracellular metabolic stress is critical for understanding pathologic processes and developing anticancer therapies. Herein, we developed ferritin-targeting proteolysis targeting chimeras (PROTACs) to establish the iron excess stress inside cancer cells and investigated subsequent cellular behaviors. We conjugated oleic acid that binds to the ferritin dimer to the ligand of von Hippel–Lindau (VHL) E3 ligase through an alkyl linker. The screened chimera, DeFer-2, degraded ferritin and then rapidly elevated the free iron content, thereby initiating the caspase 3-GSDME-mediated pyroptosis in cancer cells rather than typical ferroptosis that is always associated with iron ion overload. According to its structural and physicochemical characteristics, DeFer-2 was loaded into a tailored albumin-based nano-formulation, which substantially inhibited tumor growth and prolonged the survival time of mice bearing B16F10 subcutaneous tumors with negligible adverse effects. This study developed a ferritin-targeting PROTAC for iron overload stress, revealed iron metabolic dysregulation-mediated pyroptosis, and provided a PROTAC-based pyroptosis inducer for anticancer treatment.

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“…Accordingly, it was also found in human bodies based on the detection of the metabolites (Vogel et al, 2023). Moreover, DMPs also provoked damages on DNA in comet assays, reduction on hemoglobin content in red blood cells, and blood immunotoxicity in rats (Balabanič et al, 2021; Chi et al, 2021; Chi et al, 2022). DMPs was also among the main PAEs affecting microbial communities (Zhou et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Reproductive toxicities of dimethyl phthalates on Caenorhabditis elegans with alteration in responses over life stages

Zhang,

Huang,

et al. 2024

Land Degrad Dev

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Phthalate esters (PAEs) raised serious concerns on their health risk due to their toxicities. However, toxicities of low‐molecular‐weight PAEs, for example, dimethyl phthalates (DMPs), remained poorly investigated. In the present study, the reproductive toxicities of dimethyl (o‐)phthalate (DMOP), dimethyl (p‐)phthalate (DMPP), and dimethyl (m‐)phthalate (DMMP) were measured on Caenorhabditis elegans with mechanical exploration. Results showed that DMPP, DMOP, and DMMP commonly inhibited the total reproduction while stimulated lifespan, showing trade‐off effects. In effects on gene expressions, DMPP, DMOP, and DMMP caused different regulations on the expressions of vab‐1, ceh‐18, and gsa‐1 which are involved in oocyte growth, ovulation, and maturation. Meanwhile, they commonly downregulated those of rme‐2 and rcy‐4 that regulate germ cells and gonads and lipid metabolism in oocytes. Moreover, the effects on biochemicals that regulate reproductive processes showed alteration between stimulation and inhibition over life stages. In addition, effects at apical, biochemical, and molecular levels clearly showed the structure influences on the toxicities. Summing up, reproductive toxicities of DMPs depended on the exposure life stages and also the chemical structures.

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Revealing the toxicity of dimethyl phthalate (DMP) to the oxygen-carrying function of red blood cells (RBCs): The iron release mechanism

Cited by 21 publications

References 39 publications

Heat stress affects dairy cow health status through blood oxygen availability

Heat stress affects dairy cow health status through blood oxygen availability

Small-Molecule Ferritin Degrader as a Pyroptosis Inducer

Reproductive toxicities of dimethyl phthalates on Caenorhabditis elegans with alteration in responses over life stages

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