Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

Martínez‐Gil, Natalia; Vidal-Gil, Lorena; Flores-Bellver, Miguel; Maisto, Rosa; Sancho‐Pelluz, Javier; Díaz-Llopis, M.; Barcia, Jorge M.; Romero, Francisco J.

doi:10.3390/antiox9090776

Cited by 8 publications

(6 citation statements)

References 66 publications

(115 reference statements)

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“…Research performed by Martinez-Gil et al [ 66 ] showed that the antioxidants N-acetylcysteine and diallyl sulfide reduced ethanol-induced increases in CYP2E1 expression and superoxide anions, indicative of a decrease in oxidative stress. These results supported the DAS-induced reduction in oxidative stress in the data presented in this study and a previous study performed by Liu et al [ 67 ] that found DAS attenuated ethanol-induced increases in malonaldehyde (a by-product of lipid peroxidation), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in human hepatocytes.…”

Section: Discussionsupporting

confidence: 93%

Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

et al. 2021

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Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and 60 μM DAS, respectively. Co-treatment with DAS (60 μM and 600 μM) inhibited BaP-induced reactive oxygen species (ROS) formation by 132% and 133%, respectively, as determined by the accumulation of H2O2 in the extracellular medium and an increase in 8-OHdG levels of treated cells. All DAS concentrations inhibited BaP-induced DNA strand breaks through co-treatment and pre-treatment methods at all time points evaluated. Co-Treatment with 60 μM DAS increased DNA Pol β expression in response to BaP-induced lipid peroxidation and oxidative DNA damage. These results indicate that DAS effectively inhibited BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in an MCF-10A cell line. These results provide more experimental evidence for garlic’s antitumor abilities and corroborate many epidemiological studies regarding the association between the increased intake of garlic and the reduced risk of several types of cancer.

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Section: Discussionsupporting

confidence: 93%

Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

et al. 2021

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“…CYP2E1 is an inducible gene that is upregulated under multiple conditions, such as fasting and nutrition intake, as well as in a wide variety of pathophysiological states (2,(12)(13)(14)(15)(16)(17). In addition to metabolizing endogenous substrates and xenobiotics, CYP2E1 is the main source of cellular ROS, and its NADPH oxidase activity is higher than that of other CYP family members (9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

“…The expression level of CYP2E1 is upregulated in a wide variety of pathological states and diseases, including obesity, diabetes mellitus, alcoholic liver disease, heart diseases, inflammation, Parkinson's disease and cancer (12)(13)(14)(15)(16)(17). In view of the expression characteristic of CYP2E1, it has been used as a therapeutic target in drug discovery and already has been applied in preliminarily studies (18).…”

Section: Introductionmentioning

confidence: 99%

Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice

et al. 2021

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Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is upregulated in multiple heart diseases and causes damage mainly via the production of reactive oxygen species (ROS). In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and knockdown of endogenous CYP2E1 can attenuate the pathological development of dilated cardiomyopathy (DCM). Nevertheless, targeted inhibition of CYP2E1 via the administration of drugs for the treatment of DCM remains elusive. Therefore, the present study aimed to investigate whether diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, can be used to inhibit the development of the pathological process of DCM and identify its possible mechanism. Here, cTnT R141W transgenic mice, which developed typical DCM phenotypes, were used. Following treatment with DAS for 6 weeks, echocardiography, histological analysis and molecular marker detection were conducted to investigate the DAS-induced improvement on myocardial function and morphology. Biochemical analysis, western blotting and TUNEL assays were used to detected ROS production and myocyte apoptosis. It was found that DAS improved the typical DCM phenotypes, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, as determined using echocardiographic and histopathological analyses. Furthermore, the regulatory mechanisms, including inhibition both of the oxidative stress levels and the mitochondria-dependent apoptosis pathways, were involved in the effects of DAS. In particular, DAS showed advantages in terms of improved chamber dilation and dysfunction in model mice, and the improvement occurred in the early stage of the treatment compared with enalaprilat, an angiotensin-converting enzyme inhibitor that has been widely used in the clinical treatment of DCM and HF. The current results demonstrated that DAS could protect against DCM via inhibition of oxidative stress and apoptosis. These findings also suggest that inhibition of CYP2E1 may be a valuable therapeutic strategy to control the development of heart diseases, especially those associated with CYP2E1 upregulation. Moreover, the development of DAS analogues with lower cytotoxicity and metabolic rate for CYP2E1 may be beneficial.

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“…Given its functions and anatomical location, RPE is subjected to biomolecule photooxidation, high accumulation of phagosomes, lysosomes, lipid-protein aggregates (such as lipofuscin), and high oxygen tension, which is intensified in retinal dystrophies with loss of photoreceptors ( Sparrrow et al, 2010 ). Accordingly, the mechanisms promoted by RPE cells to counteract the oxidative stress and inflammation involve not only enzymatic defense ( Wunderlich et al, 2010 ), but also the synthesis and release of antioxidant and anti-inflammatory molecules and pro-survival growth factors ( Meyer et al, 2019 ; Martinez-Gil et al, 2020 ). The enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), peroxiredoxins (PRDXs), and other antioxidant enzymes is essential in RPE to buffer ROS ( Pintea et al, 2011 ; Fang et al, 2016 ).…”

Section: Cellular Responses In the Inherited Retinal Dystrophies In R...mentioning

confidence: 99%

Cellular and molecular alterations in neurons and glial cells in inherited retinal degeneration

et al. 2022

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Multiple gene mutations have been associated with inherited retinal dystrophies (IRDs). Despite the spectrum of phenotypes caused by the distinct mutations, IRDs display common physiopathology features. Cell death is accompanied by inflammation and oxidative stress. The vertebrate retina has several attributes that make this tissue vulnerable to oxidative and nitrosative imbalance. The high energy demands and active metabolism in retinal cells, as well as their continuous exposure to high oxygen levels and light-induced stress, reveal the importance of tightly regulated homeostatic processes to maintain retinal function, which are compromised in pathological conditions. In addition, the subsequent microglial activation and gliosis, which triggers the secretion of pro-inflammatory cytokines, chemokines, trophic factors, and other molecules, further worsen the degenerative process. As the disease evolves, retinal cells change their morphology and function. In disease stages where photoreceptors are lost, the remaining neurons of the retina to preserve their function seek out for new synaptic partners, which leads to a cascade of morphological alterations in retinal cells that results in a complete remodeling of the tissue. In this review, we describe important molecular and morphological changes in retinal cells that occur in response to oxidative stress and the inflammatory processes underlying IRDs.

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Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

Cited by 8 publications

References 66 publications

Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice

Cellular and molecular alterations in neurons and glial cells in inherited retinal degeneration

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