Obacunone attenuates high glucose-induced oxidative damage in NRK-52E cells by inhibiting the activity of GSK-3ß.
Biochem Biophys Res Commun
; 513(1): 226-233, 2019 05 21.
Article
em En
| MEDLINE
| ID: mdl-30954216
ABSTRACT
Hyperglycemia-induced proximal tubule injury plays a critical role in the pathogenesis of diabetic nephropathy (DN). Attenuating high glucose (HG)-induced oxidative damage in renal tubular epithelial cells has been documented to ameliorate DN. Obacunone (OB), a natural bioactive compound isolated from the Rutaceae family, has been demonstrated to possess various pharmacological effects with low toxicity. However, the role of OB in DN has not yet been investigated. To explore the influence of OB on oxidative damage that is induced by HG and its potential mechanisms of action, we set up a high glucose model and induced oxidative damage in NRK-52E cells. OB could protect the NRK-52E cells from the HG-induced decrease of cell viability and the accumulation of ROS. The protective effects of OB were associated with its ability to increase the levels of antioxidants (SOD, GSH and CAT), inhibit the production of ROS, and stabilize the mitochondrial membrane potential. In addition, OB significantly downregulated the activity of GSK-3ß, enhanced the nuclear translocation of Nrf2 and increased the mRNA expression of the Nrf2-driven genes NQO-1 and HO-1 in HG-treated cells. OB also decreased the release of cytochrome c from the mitochondria to the cytosol and inhibited the activation of caspase-3 in HG-treated cells. Pretreatment with a GSK-3ß activator blocked the protective effects of OB, while pretreatment with a GSK-3ß inhibitor yielded opposite results. These findings indicate that the renoprotective effects of OB against HG-induced oxidative damage in NRK-52E cells may be mediated by its ability to inhibit oxidative stress and mitochondrial dysfunction through the GSK-3ß signaling pathway.
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Base de dados:
MEDLINE
Assunto principal:
Benzoxepinas
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Estresse Oxidativo
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Limoninas
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Glicogênio Sintase Quinase 3 beta
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Glucose
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Antioxidantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article