Melatonin counteracts oxidative damage in lens by regulation of Nrf2 and NLRP3 inflammasome activity



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Lledó, Victoria Eugenia and Awad Alkozi, Hanan and Sánchez Naves, Juan and Fernández Torres, Miguel Ángel and Guzmán Aránguez, Ana Isabel (2021) Melatonin counteracts oxidative damage in lens by regulation of Nrf2 and NLRP3 inflammasome activity. Experimental Eye Research, 215 . 10 p.. ISSN 0014-4835

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Oxidative stress, generated because of an imbalance between reactive oxygen species (ROS) generation and elimination, is associated with lens damage and cataract progression. ROS generation is known to activate NLRP3(nucleotide-binding oligomerization domain-like receptor family, pyrin domain-cointaining 3) inflammasome, and is believed to be an important link between oxidative stress and inflammation, that is also related to cataract development. Potential oxidative hazard to the lens by white light-emitting diode (LED) light, a source of illu-mination commonly used nowadays, has been suggested, although available information is limited. In this work,we evaluated the cytotoxicity induced by hydrogen peroxide (an oxidative stressor agent) and white LED light in lens epithelial cells as well as melatonin ability to counteract the effects induced by them. Melatonin is a neurohormone secreted by different ocular structures that could be useful to alleviate oxidative damage induced by different oxidative stressors in lens. Particularly, the modulation of Nrf2 (nuclear erythroid 2-related factor)/Keap 1 (Kelch-like ECH-associated protein 1), an essential oxidative stress regulator, and NLRP3 activity by melatonin was evaluated in lens epithelial cells. ROS levels rose after white LED light exposure and cell viability was reduced after challenge with oxidative stressor agents. Melatonin prevented cell death triggered by hydrogen peroxide and white LED light, precluded ROS generation induced by white LED light and promoted antioxidant lens capacity through upregulation of Nrf2 protein levels and SOD activity. NLRP3, caspase-1 and IL1-β expression significantly increased in human lens cells exposed to H2O2 or irradiated with white LED light.
Activation of NLRP3 inflammasome triggered by oxidative stressors was also abrogated by melatonin. Attenuation of inflammatory and cytotoxic effects induced by oxidative stressors provided by melatonin in lens indicate the interest of this molecule as a potential therapeutic agent for cataract prevention/management

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Received 16 October 2021, Revised 19 December 2021, Accepted 22 December 2021, Available online 26 December 2021, Version of Record 30 December 2021.

Uncontrolled Keywords:Lens; Oxidative stress; Melatonin; Cataracts; White light-emitting diode light; NLRP3; Nrf2
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Ophtalmology
Medical sciences > Medicine > Optics
ID Code:69527
Deposited On:28 Mar 2022 16:39
Last Modified:30 Mar 2022 08:03

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