DHEA prevents ribavirin-induced anemia via inhibition of glucose-6-phosphate dehydrogenase

Handala, Lynda; Domange, Barbara; Ouled-Haddou, Hakim; Garçon, Loïc; Nguyen‐Khac, Eric; Helle, François; Bodeau, Sandra; Duverlie, Gilles; Brochot, Étienne

doi:10.1016/j.antiviral.2017.09.002

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…The antioxidant effects of DHEA are multi-targeted, and several explanations have been proposed, including inhibition of glucose-6-phosphate dehydrogenase (G6PD) [ 41 ], alteration of catalase expression [ 42 ], upregulation of the redox system [ 43 ], change in fatty acid composition of cell membranes, and cytokine production [ 24 ]. The existence of a high-affinity DHEA receptor-activated phosphatidyl-inositol 3-kinase/Akt pathway has also been shown [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

Mukohara

Mifune

Inui

et al. 2021

BMC Musculoskelet Disord

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Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

Mukohara

Mifune

Inui

et al. 2021

BMC Musculoskelet Disord

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“…HA/Ara‐IR820@ZIF‐8 (0.15 mL) of a series of concentrations (10, 20, 50, 100, 200, and 500 µg mL −1 ) was mixed with 2% RBCs suspension (1.25 mL) and 1.10 mL of saline. The above mixture was incubated at the temperature of 37.0 ± 1.0 °C for 3 h. After incubation, the mixture was centrifuged at 1500 rpm for 15 min, and then the absorbance of supernatant was measured using a UV–vis spectrophotometer at 540 nm . As for the positive group, the hemolysis ratio of water was tested by the mixture of 2% RBCs suspension and 1.25 mL of water.…”

Section: Methodsmentioning

confidence: 99%

A Versatile Prodrug Strategy to In Situ Encapsulate Drugs in MOF Nanocarriers: A Case of Cytarabine‐IR820 Prodrug Encapsulated ZIF‐8 toward Chemo‐Photothermal Therapy

Zhang

Liu

et al. 2018

Adv Funct Materials

199

147

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Zeolitic imidazolate framework-8 (ZIF-8) is an attractive metal organic framework (MOF) in drug delivery. Strong interaction between drugs and ZIF-8 is essential for high drug loadings through in situ construction of MOFs. However, only limited drugs with unique functional groups (COOH, SO 3 H, et al.) can interact with ZIF-8 and be encapsulated satisfactorily so far. Drugs without these functional groups are difficult to be loaded due to the lack of strong interaction. Herein a versatile prodrug strategy is proposed to solve the problems encountered by MOFs. Cytarabine (Ara) is chosen as a model drug since it cannot be loaded in ZIF-8 satisfactorily by itself. New indocyanine green (IR820) is utilized to bond with Ara for the formation of prodrug (Ara-IR820) and endows the prodrug with fluorescence imagingguided chemo-photothermal therapy, in which sulfonic groups strengthen the interaction between prodrug and ZIF-8. This prodrug loaded ZIF-8 is further functionalized with hyaluronic acid (HA) to result in active-targeting HA/ Ara-IR820@ZIF-8 nanoparticles. The in vitro and in vivo results demonstrate its excellent visual cancer therapy with tumor-targeted and pH-responsive release behavior. This design offers a new concept to solve the drug loading problem of MOFs, exhibiting a flexible strategy to expand the biomedical applications of MOFs.

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“…DHEAS is the more stable sulfate ester form of DHEA in the blood, and both can be interconverted into each other via de-sulfation/sulfation via the action of hydroxysteroid sulfur transferase (HST) or steroid sulfatase (STS), respectively [ 21 , 22 ]. As a metabolic precursor for the synthesis of steroid androgen and estrogen [ 23 ], DHEA possesses uncompetitive inhibition activity of G6PD, thus targeting the PPP [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

G6PD promotes cell proliferation and dexamethasone resistance in multiple myeloma via increasing anti-oxidant production and activating Wnt/β-catenin pathway

et al. 2022

Exp Hematol Oncol

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Background Glucose-6-phosphate dehydrogenase (G6PD) as the rate-limiting enzyme in the pentose phosphate pathway (PPP) is well-established as an aberrantly expressed protein in numerous clinical diseases; however, its role in cancer, specifically in multiple myeloma (MM) remains elusive. Methods In this study, serum metabolites in 70 normal people and 70 newly diagnosed MM patients were analyzed using untargeted metabolomics and the results were verified using ELISA. The survival analysis of multiple clinical datasets was performed to identify a potential target gene in MM. The oncogenic role of G6PD was investigated using lentivirus-based overexpression or knockdown of G6PD using RNAi or an inhibitor in vitro, and in a xenograft mouse model in vivo. The mechanisms of induced Dexamethasone (Dexa)-resistance of G6PD were further explored using the above established MM cell lines in vitro. Results Based on the screening of potential genes, PPP was shown to be involved in the occurrence of MM, which was evidenced by the differential expression of serum metabolites of G6P and Dehydroepiandrosterone sulfate (DHEAS, the more stable sulfate ester form of an endogenously uncompetitive G6PD inhibitor known as DHEA). Elevated G6PD promoted MM cell proliferation. Mechanistically, high G6PD expression enhanced enzymatic generation of the antioxidant NADPH via the PPP and decreased the production of reactive oxygen species (ROS), thus inducing the proliferation and Dexa resistance in MM cells. Furthermore, canonical Wnt/β-catenin signaling also participated in regulating G6PD-induced drug resistance and cellular redox levels of ROS. Intriguingly, DHEA treatment could enhance the sensitivity of MM cells to Dexa primarily through augmenting cellular oxidative stress. Conclusions Our data demonstrate that G6PD enhances the generation of the enzymatic anti-oxidant NADPH and decreases ROS generation, thereby promoting resistance to Dexa-induced apoptosis via the enzymatic PPP and non-enzymatic Wnt/β-catenin signaling pathway in MM. Targeting G6PD to harness cellular redox may serve as a promising novel strategy for the management of MM.

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DHEA prevents ribavirin-induced anemia via inhibition of glucose-6-phosphate dehydrogenase

Cited by 8 publications

References 41 publications

In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

A Versatile Prodrug Strategy to In Situ Encapsulate Drugs in MOF Nanocarriers: A Case of Cytarabine‐IR820 Prodrug Encapsulated ZIF‐8 toward Chemo‐Photothermal Therapy

G6PD promotes cell proliferation and dexamethasone resistance in multiple myeloma via increasing anti-oxidant production and activating Wnt/β-catenin pathway

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