Attenuation of tert-Butyl Hydroperoxide (t-BHP)-Induced Oxidative Damage in HepG2 Cells by Tangeretin: Relevance of the Nrf2–ARE and MAPK Signaling Pathways

Abstract

The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide ( t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK-Nrf2-ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.

Isoflavone biochanin A, a novel nuclear factor erythroid 2‐related factor 2 (Nrf2)‐antioxidant response element activator, protects against oxidative damage in HepG2 cells

“…In brief, HepG2 cells (10 5 cells/well) were seeded in 24‐well plates. After pretreatment of cells with BCA (3, 6, and 12 μM) for 24 h, ROS levels were determined as described in our previous study …”

“…Immunofluorescent assay was performed according to our previous study. 17 Briefly, after treatment with or without 12 μM BCA, HepG2 cells were fixed with 4% (v/v) paraformaldehyde (30 min), permeabilized with 0.1% (w/v) Triton X-100 for 10 min, and then blocked with 5% bovine serum albumin for 1 hr. The cells were incubated with anti-Nrf2 antibody overnight (4 C) and subsequently incubated with Cy3-labeled secondary antibody.…”

Dynorphin activation of kappa opioid receptor protects against epilepsy and seizure-induced brain injury via PI3K/Akt/Nrf2/HO-1 pathway

“…Indeed, significant levels of free radicals and oxidative damage have been observed in the brain during seizures [11,12]. As one of the most important antioxidant pathways [13,14], the nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) (Nrf2/HO-1) pathway has been recently shown to exert a significantly neuroprotective role in epilepsy [15,16]. Under normal conditions, Nrf2 is located in the cytoplasm as an inactive complex bound to the repressor protein named as Kelch-like ECH-associated protein 1 (Keap1); Under oxidative/electrophilic stress, Nrf2 dissociates from Keap1, then translocates to the nucleus where it binds to the antioxidant response element (ARE) to regulate the transcription of numerous antioxidant and cytoprotective genes, such as HO-1 and superoxide dismutase 1 (SOD1) [17,18].…”

Yogurt and Streptococcus thermophilus metabolites ameliorated telomere attrition in D‐galactose‐induced ageing mice and t‐BHP‐challenged HepG2 cells

“…In order to substantiate the effects of yogurt and S. thermophilus metabolites at cellular level, oxidative damage was introduced to human HepG2 cells by challenging with t ‐BHP (Liang et al , ). In agreement with animal experiments, yogurt and metabolites of S. thermophilus and L. rhamnosus significantly reduced senescent cell numbers, while milk showed minimal effect compared to the model.…”

“…Abnormal level of D‐galactose in rodents would increase the accumulation of reactive oxygen species, thus damaging cell structure and shortening the telomere (Ho et al , ; Chen et al , ). Similarly, tert ‐butyl hydroperoxide ( t ‐BHP) was recruited to produce free radicals and induce telomere loss in cell studies (Boesten et al , ; Liang et al , ). Accordingly, the aim of this study was to explore whether yogurt and metabolites of typical dairy‐fermenting bacteria affect relative telomere length in ageing mice and t ‐BHP‐challenged HepG2 cells.…”