Chronic oral depleted uranium leads to reproductive damage in male rats through the ROS-hnRNP A2/B1-COX-2 signaling pathway

Lu, Binghui; Ran, Yonghong; Wang, Shuang; Li, Juan; Zhao, Yazhen; Ran, Xinze; Li, Rong; Hao, Yuhui

doi:10.1016/j.tox.2020.152666

Cited by 11 publications

(7 citation statements)

References 48 publications

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“…e examination believe that this phenomenon may be that the expression standard of hnRNP A2/B1 during cell proliferation is regulated by differentiation in different cell proliferation stages, causing lung cancer due to regulatory disorders [12,13].…”

Section: Related Workmentioning

confidence: 99%

“…HnRNP A2/B1 is expressed at very low or even no expression standards in normal bronchial epithelial cells, but is elevated in the central airway and metaplastic epithelial tissues of chronic smokers and notoriously subjoined in lung cancer tissues. The examination believe that this phenomenon may be that the expression standard of hnRNP A2/B1 during cell proliferation is regulated by differentiation in different cell proliferation stages, causing lung cancer due to regulatory disorders [ 12 , 13 ]. The present examination found that with the increase of the stage, its positive expression rate was notoriously subjoined, and there is an extensive disparity.…”

Section: Related Workmentioning

confidence: 99%

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[Retracted] The Expression of hnRNP A2/B1 in Benign and Malignant Lung Lesions and Its Early Diagnosis Value in NSCLC

Gao

Wang

et al. 2022

Contrast Media & Molecular Imaging

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Lung cancer in its occurrence and development of different stages exist different biological behavior changes. This paper studies the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 in benign and malignant lung lesions and its early diagnosis value of nonsmall-cell lung cancer (NSCLC), aiming to provide reference for the early diagnosis and therapy of NSCLC. Some lung surgery specimens are selected from January 2021 to March 2022. All cases received no radiotherapy and chemotherapy before surgery, including 90 sufferers with benign lung lesions as the contrast set. hnRNP A2/B1 expressions are measured for comparison. The experimental results show that for lung cancer sufferers, the positive expression of hnRNP A2/B1 in their malignant lesion tissue is notoriously higher than that in their benign lesion tissue, and hnRNP A2/B1 is differently expressed in different differentiation and in different stages.

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Section: Related Workmentioning

confidence: 99%

Section: Related Workmentioning

confidence: 99%

[Retracted] The Expression of hnRNP A2/B1 in Benign and Malignant Lung Lesions and Its Early Diagnosis Value in NSCLC

Gao

Wang

et al. 2022

Contrast Media & Molecular Imaging

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“…The challenge posed by UA has been linked to negative modulation in the pituitary–gonadal axis, as indicated in prior reports 32 , 33 . This outcome is associated with the down-regulation of genes encoding enzymes involved in steroid production, signal transduction, and LH receptor activity 34 , 35 .…”

Section: Discussionmentioning

confidence: 88%

“…The histopathological perturbations observed in our investigation align with earlier studies suggesting that UA exposure triggers adverse cytological alterations in the testis 48 , 63 . Inhibition of enzymes associated with sperm synthesis, maturation, and energy metabolism 32 , 33 might contribute to the presence of azoospermia in some seminiferous tubules. The reduction in FSH leads to spermatogenic disorders, given its vital role in initiating and maintaining spermatogenesis and nurturing developing germ cells by Sertoli cells 64 , 65 .…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Moringa oleifera leaf ethanolic extract against uranyl acetate-induced testicular dysfunction in rats

Ragab,

Almohaimeed,

Alghriany

et al. 2024

Sci Rep

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Uranyl acetate (UA) is used in civilian and military applications, predisposing it to wide dispersion in ecosystems. Using high-performance liquid chromatography, gas chromatography–mass spectrometry, and 2,2-Diphenyl-1-picrylhydrazyl scavenging radical analysis, we confirmed that Moringa oleifera leaf ethanolic extract (MLEE) is rich in biologically active phytochemicals. Thus, this study aims to investigate the possible defensive effect of MLEE against UA-induced testicular dysfunction. To achieve this, rats were divided randomly and evenly into three groups for 14 days. The control group received no treatment, while the UA group received a single intraperitoneal injection of UA at a dose of 5 mg/kg BW dissolved in saline on the 12th day of the experiment, followed by no treatment the following day. The MLEE + UA group received daily oral administration of MLEE (300 mg/kg BW) dissolved in distilled water before exposure to UA intoxication. The disruption observed in the pituitary–gonadal axis of UA-intoxicated rats was characterized by a significant decrease in luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol 17beta levels. Additionally, there was a notable increase in malondialdehyde and a decrease in catalase, superoxide dismutase, reduced glutathione, and nitric oxide, accompanied by an up-regulation in the immuno-expression of nuclear factor-kappa B, indicating a disturbance in the redox balance. The TUNEL assay confirmed a substantial rise in apoptotic cell numbers in the UA group. Testicular histopathological changes, excessive collagen deposition, and reduced glycogen content were evident following UA exposure. However, supplementation with MLEE effectively countered these mentioned abnormalities. MLEE is proposed to combat the toxicological molecular targets in the UA-affected testis by restoring the balance between oxidants and antioxidants while obstructing the apoptotic cascade. MLEE contains an abundance of redox-stabilizing and cytoprotective phytochemicals that have the potential to counteract the mechanistic pathways associated with UA exposure. These findings encourage further research into other plausible protective aspects of Moringa oleifera against the UA challenge.

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“…Numerous studies have shown that excessive ROS was the main factor in DU-induced cytotoxicity. 5,6 Some studies suggested that DU could result in toxicity by aggravating oxidative stress, followed by lipid peroxidation and glutathione oxidation. 30 Hh signaling crosstalk with ROS formation, that is, ROS controls Hh expression and that Hh in turn regulates ROS level.…”

Section: Discussionmentioning

confidence: 99%

Hedgehog pathway negatively regulated depleted uranium‐induced nephrotoxicity

Xie,

Fu,

Liu

et al. 2024

Environmental Toxicology

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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.

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Chronic oral depleted uranium leads to reproductive damage in male rats through the ROS-hnRNP A2/B1-COX-2 signaling pathway

Cited by 11 publications

References 48 publications

[Retracted] The Expression of hnRNP A2/B1 in Benign and Malignant Lung Lesions and Its Early Diagnosis Value in NSCLC

[Retracted] The Expression of hnRNP A2/B1 in Benign and Malignant Lung Lesions and Its Early Diagnosis Value in NSCLC

Protective effect of Moringa oleifera leaf ethanolic extract against uranyl acetate-induced testicular dysfunction in rats

Hedgehog pathway negatively regulated depleted uranium‐induced nephrotoxicity

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