Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis

Hu, Xin; Liang, Yuanyuan; Zhao, Bo; Wang, Yong-Yi

doi:10.1002/jcb.27739

Cited by 30 publications

(30 citation statements)

References 26 publications

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“…These results support TPP-Niacin as a potent antioxidant against oxidative stress compared to niacin and suggest that its improved protective effects are exerted via regulation of mitochondrial dynamics and antioxidant mechanisms. Contrary to expectations, the increment of antioxidant enzymes after induction of oxidative stress was in agreement with the study where the expression levels of HO-1 increased in ARPE-19 cells after H 2 O 2 treatment [44,45,[47][48][49]. However, some studies have presented that H 2 O 2 treatment signi cantly reduces the expression levels of PGC-1α, HO-1, and NQO-1 in ARPE-19 cells [38,41].…”

Section: Discussionsupporting

confidence: 89%

“…On further investigating the possible mechanisms associated with the protective ability of TPP-Niacin, it appears that HO-1 and NQO-1, which are downstream targets of NRF2 signaling, play major roles in the prevention of oxidative damage in the cells [39,40]. Recently, many studies have reported that the activation of NRF2/HO-1 signaling is required to alleviate oxidative damages in RPE cells [41,42] [43][44][45][46]. In this study, it was speculated that the antioxidative effects of TPP-Niacin could be combined with PGC-1α and NRF2 signaling.…”

Section: Discussionmentioning

confidence: 99%

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Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

KIM

Kim

Yang

et al. 2020

Preprint

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Background: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells.Methods: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR). Results: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1).Conclusion: We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

KIM

Kim

Yang

et al. 2020

Preprint

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“…In particular, in wild type and Nrf2-deficient ARPE-19 cells, we studied the effects of the following pro-oxidant AMD-related noxae: H 2 O 2 , 4-hydroxynonenal (4-HNE), MG132 + Bafilomycin. H 2 O 2 is a strong oxidant leading to an immediate ROS production, widely used in in vitro study on RPE cells (Zhu et al, 2017;Hu et al, 2019;Zhao et al, 2019), that are physiologically subjected to elevated ROS levels due to their high metabolism and functions (Strauss, 2005). 4-HNE is a product of lipid peroxidation accumulating in AMD retina (Ethen et al, 2007); it is pro-oxidant and toxic for RPE (Kaarniranta et al, 2005;Kaemmerer et al, 2007;Chen et al, 2009), but its effects on Nrf2-pathway have been not fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium

et al. 2020

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Age-related macular degeneration (AMD) is a common disease with a multifactorial aetiology, still lacking effective and curative therapies. Among the early events triggering AMD is the deterioration of the retinal pigment epithelium (RPE), whose fundamental functions assure good health of the retina. RPE is physiologically exposed to high levels of oxidative stress during its lifespan; thus, the integrity and well-functioning of its antioxidant systems are crucial to maintain RPE homeostasis. Among these defensive systems, the Nrf2-pathway plays a primary role. Literature evidence suggests that, in aged and especially in AMD RPE, there is an imbalance between the increased pro-oxidant stress, and the impaired endogenous detoxifying systems, finally reverberating on RPE functions and survival. In this in vitro study on wild type (WT) and Nrf2-silenced (siNrf2) ARPE-19 cells exposed to various AMD-related noxae (H 2 O 2 , 4-HNE, MG132 + Bafilomycin), we show that the Nrf2-pathway activation is a physiological protective stress response, leading downstream to an up-regulation of the Nrf2targets HO1 and p62, and that a Nrf2 impairment predisposes the cells to a higher vulnerability to stress. In search of new pharmacologically active compounds potentially useful for AMD, four nature-inspired hybrids (NIH) were individually characterized as Nrf2 activators, and their pharmacological activity was investigated in ARPE-19 cells. The Nrf2 activator dimethyl-fumarate (DMF; 10 mM) was used as a positive control. Three out of the four tested NIH (5 mM) display both direct and indirect antioxidant properties, in addition to cytoprotective effects in ARPE-19 cells under pro-oxidant stimuli. The observed pro-survival effects require the presence of Nrf2, with the exception of the lead compound NIH1, able to exert a still significant, albeit lower, protection even in siNrf2 cells, supporting the concept of the existence of both Nrf2-dependent and independent pathways mediating pro-survival effects. In conclusion, by using some pharmacological tools as well as a reference compound, we dissected the role of the Nrf2-pathway in ARPE-19 stress response, suggesting that the Nrf2 induction represents an efficient defensive strategy to prevent the stressinduced damage.

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“…e extract of N. sativa seeds could restore the activities of these parameters to near normal [60]. In a e results indicated that thymoquinone could protect ARPE cells from H 2 O 2 -induced oxidative stress through the Nrf2/HO-1 pathway [62]. Furthermore, a recent study was conducted on forty patients with Hashimoto's thyroiditis to evaluate the effect of powdered N. sativa seeds (1 g/day for 8 week) on oxidative stress.…”

Section: Pharmacological Effectsmentioning

confidence: 99%

Recent Progress on Chemical Constituents and Pharmacological Effects of the Genus Nigella

Niu

Zhou

Meng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Seeds of the genus Nigella plants as folk medicine are often used to prevent and treat asthma, diarrhea, dyslipidemia, and other diseases around the world. Pharmacological researches showed that seed extract and seed oil have antibacterial, antioxidant, hypoglycemic, and hepatoprotective effects which attributed to their bioactive constituents such as alkaloids, saponins, flavones, and phenols. This paper has covered recent progresses on chemical and pharmacological researches on these plants, including their compounds and pharmacological effects. It was found that the chemical component researches were focused on the seed oil. Therefore, more attention should be paid to the profile of the whole constituents in the seeds.

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Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis

Cited by 30 publications

References 26 publications

Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium

Recent Progress on Chemical Constituents and Pharmacological Effects of the Genus Nigella

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