Depleted uranium causes renal mitochondrial dysfunction through the ETHE1/Nrf2 pathway

Liu, Suiyi; Wang, Shuang; Zhao, Yazhen; Li, Juan; Shu, Chang; Li, Yong; Li, Jie; Lu, Binghui; Xu, Zeheng; Ran, Yonghong; Hao, Yuhui

doi:10.1016/j.cbi.2023.110356

Cited by 9 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The kidney is a key organ in maintaining ion and fluid homeostasis, eliminating metabolic degradation products. Besides, kidney and more specifically the tubular epithelial cells were reported as the primary target for the chemical toxicity of DU, ending with renal dysfunction and damage of the tubular cells 7,8 . For example, Hao et al demonstrated that DU could induce cytotoxicity towards HEK‐293 T cells by activating nucleus p53 and inhibiting mTOR signal 9 .…”

Section: Introductionmentioning

confidence: 99%

Hedgehog pathway negatively regulated depleted uranium‐induced nephrotoxicity

Xie,

Fu,

Liu

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

Depleted uranium (DU) retains the radiological toxicities, which accumulates preferentially in the kidneys. Hedgehog (Hh) pathway plays a critical role in tissue injury. However, the role of Hh in DU‐induced nephrotoxicity was still unclear. This study was carried out to investigate the effect of Gli2, which was an important transcription effector of Hh signaling, on DU induced nephrotoxicity. To clarify it, CK19 positive tubular epithelial cells specific Gli2 conditional knockout (KO) mice model was exposed to DU, and then histopathological damage and Hh signaling pathway activation was analyzed. Moreover, HEK‐293 T cells were exposed to DU with Gant61 or Gli2 overexpression, and cytotoxicity of DU as analyzed. Results showed that DU caused nephrotoxicity accompanied by activation of Hh signaling pathway. Meanwhile, genetic KO of Gli2 reduced DU‐induced nephrotoxicity by normalizing biochemical indicators and reducing Hh pathway activation. Pharmacologic inhibition of Gli1/2 by Gant61 reduced DU induced cytotoxicity by inhibiting apoptosis, ROS formation and Hh pathway activation. However, overexpression of Gli2 aggravated DU‐induced cytotoxicity by increasing the levels of apoptosis and ROS formation. Taken together, these results revealed that Hh signaling negatively regulated DU‐inducted nephrotoxicity, and that inhibition of Gli2 might serve as a promising nephroprotective target for DU‐induced kidney injury.

show abstract

Section: Introductionmentioning

confidence: 99%

Hedgehog pathway negatively regulated depleted uranium‐induced nephrotoxicity

Xie,

Fu,

Liu

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

Mitochondrial‐Targeting Mesoporous Polydopamine Nanoparticles for Reducing Kidney Injury Caused by Depleted Uranium

Li,

Shen,

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Depleted uranium (DU), when accidentally released from the nuclear industry, can enter the human body and cause kidney damage, as DU induces oxidative damage and apoptosis through mitochondrial pathways and inflammatory reactions. The existing nanoparticles used to treat DU injury have low bioavailability and poor targeting. In this study, mesoporous polydopamine (MPDA), poly‐(ethylene glycol) (PEG), and triphenylphosphonium (TPP) are combined to develop a novel mitochondrion‐targeting bifunctional nanoparticle, MPDA–PEG–TPP, and confirm that it can protect the kidneys from DU. This study demonstrates the high selectivity of MPDA–PEG–TPP for uranyl in uranyl chelate assays and its promising efficiency in uranyl sequestration from the kidneys, lungs, and femurs, following immediate or delayed administration of MPDA–PEG–TPP nanoparticles. In vitro assays confirm its efficiency in removing reactive oxygen species and targeting the mitochondria. In addition, in vitro and in vivo assays confirm that MPDA–PEG–TPP can reduce mitochondrial dysfunction and ameliorate kidney injury. These results suggest that MPDA–PEG–TPP is a valuable agent for ameliorating the DU‐induced kidney injury.

show abstract

Health Implications of Depleted Uranium: An Update

Wang,

Li,

Fan

et al. 2024

J of Applied Toxicology

View full text Add to dashboard Cite

Depleted uranium (DU), as a heavy metal material extensively utilized in the industrial sector, poses potential health risks to humans through various exposure pathways, including inhalation, ingestion, and dermal contact. To comprehensively understand the toxicological hazards of DU, this study conducted a literature search in the Web of Science Core Collection database using “DU” and “toxicity” as keywords, covering the period from January 2000 to December 2023. A total of 65 papers related to human, animal, or cellular studies on DU were included. This review delves into the latest research advancements on the origin and toxicokinetics of DU, as well as its pulmonary toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, hepatotoxicity, reproductive toxicity, cancer, bone toxicity, and hematological toxicity. The aim of this review is to gain a deeper understanding of the health hazards posed by DU, which is of significant importance for formulating corresponding protection strategies and measures.

show abstract

Depleted uranium causes renal mitochondrial dysfunction through the ETHE1/Nrf2 pathway

Cited by 9 publications

References 51 publications

Hedgehog pathway negatively regulated depleted uranium‐induced nephrotoxicity

Hedgehog pathway negatively regulated depleted uranium‐induced nephrotoxicity

Mitochondrial‐Targeting Mesoporous Polydopamine Nanoparticles for Reducing Kidney Injury Caused by Depleted Uranium

Health Implications of Depleted Uranium: An Update

Contact Info

Product

Resources

About