Zidovudine protects hyperosmolarity-stressed human corneal epithelial cells via antioxidant pathway

Liu, Hui; Gambino, Frank; Algenio, Crystal S.; Bouchard, Charles S.; Qiao, Liang; Bu, Pengcheng

doi:10.1016/j.bbrc.2018.03.112

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…In recent years, the critical role of oxidative stress in the pathogenesis of dry eye is supported by more and more evidence. Liu [29] et al found that ROS production increased signi cantly in hypertonic medium. A water-soluble CENPembedded contact lens (CENP-CL) was developed by Cui et al for the prevention of ocular surface diseases, which can remove ROS [30] .…”

Section: Discussionmentioning

confidence: 99%

BMSC reduces ROS and inflammation levels by inhibiting TLR4/MYD88/NF-κB signaling axis to alleviate dry eye

Zhao

et al. 2023

Preprint

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Objective To investigate the therapeutic effect of Bone marrow mesenchymal stem cells (BMSCs) on dry eye mice, and to investigate the mechanism of TLR4/MYD88/NF-κB signaling pathway on corneal injury repair in dry eye mice. Methods To establish a hypertonic dry eye cell model. Western blot for measureing the protein expressions of caspase-1, IL-1β，NLRP3 and ASC，and Rt-qpcr for mRNA expression. Flow cytometry for detecting the ROS content and apoptosis rate. CCK-8 for detecting the proliferation activity of cells, and ELISA for the levels of inflammation-related factors.The levels of inflammation-related factors were detected by ELISA. The dry eye mouse model of benzalkonium chloride was established. Three clinical parameters used to evaluate ocular surface damage, namely tear secretion, tear film rupture time and corneal sodium fluorescein staining, were measured with phenol cotton thread. Flow cytometry and TUNEL staining are both for he apoptosis rate. Western blot also for detecting the protein expressions of TLR4, MYD88, NF-κB, inflammation-related factors and apoptosis-related factors . The pathological changes were evaluated by HE and PAS staining. Results In vitro, BMSCs and inhibitors of TLR4, MYD88 and NF-κB showed decreased ROS content, decreased inflammatory factor protein level, decreased apoptotic protein level and increased mRNA expression compared with NaCl group. BMSCS partially reversed cell apoptosis induced by NaCl and improved cell proliferation. In vivo, it reduces corneal epithelial defects, goblet cell loss and inflammatory cytokine production, and increases tear production. In vitro, BMSC and inhibitors of TLR4, MYD88 and NF-κB could protect mice from apoptosis induced by hypertonic stress. In terms of mechanism, NACL-induced NLRP3 inflammasome formation, caspase-1 activation and IL-1β maturation can be inhibited. Conclusion BMSCs treatment can reduce ROS and inflammation levels and alleviate dry eye by inhibiting TLR4/MYD88/NF-κBsignaling pathway.

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Section: Discussionmentioning

confidence: 99%

BMSC reduces ROS and inflammation levels by inhibiting TLR4/MYD88/NF-κB signaling axis to alleviate dry eye

Zhao

et al. 2023

Preprint

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“…In H 2 O 2 -treated rabbit corneal epithelial cells, taurine significantly reduced ROS production [126]. Calcitriol [15], L-carnitine [127], and zidovudine [128] can also significantly attenuate hyperosmotic stressinduced oxidative stress and cellular inflammation in HCECs. In addition, there are numerous plant extracts that significantly attenuate oxidative stress in in vitro dry eye models, such as olive pomace extracts [129], thymoquinone [130], and pterostilbene [131].…”

Section: Other Antioxidants In Protecting Against Dedmentioning

confidence: 95%

Potential New Target for Dry Eye Disease—Oxidative Stress

Bu,

Liu,

Zhang

et al. 2024

Antioxidants

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Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by loss of tear film homeostasis and accompanied by ocular symptoms that may potentially result in damage to the ocular surface and even vision loss. Unmodifiable risk factors for DED mainly include aging, hormonal changes, and lifestyle issues such as reduced sleep duration, increased screen exposure, smoking, and ethanol consumption. As its prevalence continues to rise, DED has garnered considerable attention, prompting the exploration of potential new therapeutic targets. Recent studies have found that when the production of ROS exceeds the capacity of the antioxidant defense system on the ocular surface, oxidative stress ensues, leading to cellular apoptosis and further oxidative damage. These events can exacerbate inflammation and cellular stress responses, further increasing ROS levels and promoting a vicious cycle of oxidative stress in DED. Therefore, given the central role of reactive oxygen species in the vicious cycle of inflammation in DED, strategies involving antioxidants have emerged as a novel approach for its treatment. This review aims to enhance our understanding of the intricate relationship between oxidative stress and DED, thereby providing directions to explore innovative therapeutic approaches for this complex ocular disorder.

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“…3 It has excellent bioavailability (>90%) and penetrates cerebrospinal uid and hepatic abscesses. Zidovudine (AZT) belongs to the class of nucleoside reverse-transcriptase inhibitors (NRTIs), 4 and it is a pyrimidine synthetic analogue active against human immunodeciency virus type 1 (HIV-1). 5 Zidovudine has been approved for the treatment of HIV-1, and even helping with prevention of maternal-fetal HIV-1 transmission.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of fluorescent drug molecules for competitive binding assay based on molecularly imprinted polymers

et al. 2019

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Zidovudine protects hyperosmolarity-stressed human corneal epithelial cells via antioxidant pathway

Cited by 8 publications

References 23 publications

BMSC reduces ROS and inflammation levels by inhibiting TLR4/MYD88/NF-κB signaling axis to alleviate dry eye

BMSC reduces ROS and inflammation levels by inhibiting TLR4/MYD88/NF-κB signaling axis to alleviate dry eye

Potential New Target for Dry Eye Disease—Oxidative Stress

Synthesis of fluorescent drug molecules for competitive binding assay based on molecularly imprinted polymers

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