p-Chloro-diphenyl diselenide modulates Nrf2/Keap1 signaling and counteracts renal oxidative stress in mice exposed to repeated dexamethasone administrations.

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Publisher: NRC Research Press
Document Type: Report
Length: 6,483 words
Lexile Measure: 1370L

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Abstract :

Dexamethasone is a synthetic glucocorticoid that has been associated with oxidative stress in central and peripheral tissues. p-Chloro-diphenyl diselenide ([(p-ClPhSe).sub.2]) is an antioxidant organoselenium compound. The present study evaluated whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1) signaling contributes to the [(p-ClPhSe).sub.2] antioxidant effects in the kidney of mice exposed to dexamethasone. Adult Swiss mice received dexamethasone (intraperitoneal) at a dose of 2 mg/kg or its vehicle for 21 days. After that, mice were treated with [(p- ClPhSe).sub.2] (intragastric) (1, 5, or 10 mg/kg) for 7 days. Samples of kidneys were collected for biochemical assays. [(p-ClPhSe).sub.2] at a dose of 1 mg/kg reversed the renal reactive oxygen species (ROS) and carbonyl protein (CP) levels increased by dexamethasone. [(p-ClPhSe).sub.2] at doses of 5 and 10 mg/kg was effective against the increase of thiobarbituric acid reactive substances, ROS, and CP, as well as the decrease of [delta]-aminolevulinic acid dehydratase activity and nonprotein sulfhydryl levels induced by dexamethasone. At 5 mg/kg, [(p-ClPhSe).sub.2] reduced the renal levels of 4-OH-2-HNE and heme oxygenase (HO-1), as well as modulated the Nrf2/Keap-1 signaling in mice exposed to dexamethasone. The present findings revealed that [(p-ClPhSe).sub.2] antioxidant effects were associated with the modulation of Nrf2/Keap-1 signaling pathway in the kidney of mice exposed to dexamethasone. Key words: glucocorticoid, kidney, antioxidant, organoselenium, Nrf2/Keap-1 La dexamethasone est un glucocorticoide synthetique que l'on a associe au stress oxydatif dans les tissus centraux et peripheriques. Le p-chlorodiphenyle diselenide [(p-ClPhSe).sub.2] est un compose d'organoselenium antioxydant. La presente etude visait a evaluer si la voie de signalisation Nrf2/Keap-1 participe aux effets antioxydants du [(p-ClPhSe).sub.2] dans les reins de souris exposes a la dexamethasone. Nous avons administre de la dexamethasone a 2 mg/kg par voie i.p. ou son vehicule pendant 21 jours a des souris suisses adultes. Ensuite, nous avons administre aux souris du [(p-ClPhSe).sub.2] par voie i.g. a 1, 5 ou 10 mg/kg pendant 7 jours. Nous avons preleve des echantillons renaux en vue d'etudes biochimiques. Le [(p-ClPhSe).sub.2] a 1 mg/kg permettait d'inverser l'augmentation des taux renaux de derives reactifs de l'oxygene (ou ROS pour ) et de proteine carbonyl (PC) entrainee par la dexamethasone. Le [(p-ClPhSe).sub.2] a 5 et a 10 mg/kg etait efficace contre la hausse des derives reactifs de l'acide thiobarbiturique, des ROS et de la PC, de meme que contre l'abaissement de l'activite de l'acide [delta]-aminolevulinique deshydratase ([delta]-ALA-D) et des taux de thiols (SH) non-proteiques (NPSH) entraines par la dexamethasone. Le [(p-ClPhSe).sub.2] a raison de 5 mg/kg entrainait une diminution des taux renaux de 4-OH-2-HNE et de HO-1 de meme qu'une modulation de la voie de signalisation Nrf2/Keap-1 chez les souris exposees a la dexamethasone. Les presents resultats ont montre que les effets antioxydants du [(p-ClPhSe).sub.2] etaient associes avec la modulation de la voie de signalisation Nrf2/Keap-1 dans les reins de souris exposes a la dexamethasone.[Traduit par la Redaction] Mots-cles : glucocorticoide, rein, antioxydant, organoselenium, Nrf2/Keap-1

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Gale Document Number: GALE|A713181406