Differential roles of 3-Hydroxyflavone and 7-Hydroxyflavone against nicotine-induced oxidative stress in rat renal proximal tubule cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2017

Differential roles of 3-Hydroxyflavone and 7-Hydroxyflavone against nicotine-induced oxidative stress in rat renal proximal tubule cells

Bidisha Sengupta
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Mehdi Sahihi
Monireh Dehkhodaei
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Darrian Kelly
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Istvan Arany
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Résumé

Plant flavonoids are well known as antioxidants against oxidative stress induced by exposure to external pollutants. Nicotine (NIC) is one of those agents which increases renal oxidative stress, an important factor in the pathogenesis of renal epithelial injury in smokers. Although several studies had been conducted on flavonoids and oxidative stress, the mechanism of the protective pathways are not fully understood. Here, we present studies on antioxidant properties of two mono-hydroxyflavone isomers, 3-hydroxyflanove (3HF)- and 7-hydroxyflavone (7HF), against nicotine-associated oxidative stress and injury in cultured renal proximal tubule cells and correlate their antioxidant properties with their chemical structure. Our data clearly demonstrates, for the first time, that while both 3HF and 7HF protect renal cells from NIC-associated cytotoxicity, the mechanism of their action is different: 3HF elicits protective activity via the PKA/CREB/MnSOD pathway while 7HF does so via the ERK/Nrf2/HO-1 pathway. Molecular docking and dynamics simulations with two major signaling pathway proteins showed significant differences in the binding energies of 3HF (-5.67 and -7.39 kcal.mol-1) compared to 7HF (-5.41 and -8.55 kcal.mol-1) in the matrices of CREB and Keap1-Nrf2 proteins respectively, which corroborate with the observed differences in their protective properties in the renal cells. The implications of this novel explorative study is likely to promote the understanding of the mechanisms of the antioxidative functions of different flavones.

Domaines

Chimie
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Dates et versions

hal-04086673 , version 1 (02-05-2023)

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Citer

Bidisha Sengupta, Mehdi Sahihi, Monireh Dehkhodaei, Darrian Kelly, Istvan Arany. Differential roles of 3-Hydroxyflavone and 7-Hydroxyflavone against nicotine-induced oxidative stress in rat renal proximal tubule cells. PLoS ONE, 2017, 12 (6), pp.e0179777. ⟨10.1371/journal.pone.0179777⟩. ⟨hal-04086673⟩
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