Effects of atorvastatin and resveratrol against the experimental endometriosis; evidence for glucose and monocarboxylate transporters, neoangiogenesis

Bahrami, Ako; Ayen, Esmail; Razi, Mazdak; Behfar, Mehdi

doi:10.1016/j.lfs.2021.119230

Cited by 18 publications

(21 citation statements)

References 47 publications

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“…In particular, GLUT inhibitors may be an attractive target for the nonhormone-based treatment of endometriosis ( McKinnon et al 2014 ). The mRNA levels of GLUT1/3 and MCT1/4 were decreased in atorvastatin and resveratrol sole and simultaneous-treated groups in experimental endometriosis models ( Bahrami et al 2021 ). Atorvastatin did not cause significant changes during the glucose tolerance test, but coadministration of atorvastatin and resveratrol suppressed glycolysis and neovascularization ( Bahrami et al 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…The mRNA levels of GLUT1/3 and MCT1/4 were decreased in atorvastatin and resveratrol sole and simultaneous-treated groups in experimental endometriosis models ( Bahrami et al 2021 ). Atorvastatin did not cause significant changes during the glucose tolerance test, but coadministration of atorvastatin and resveratrol suppressed glycolysis and neovascularization ( Bahrami et al 2021 ). The simultaneous administration of atorvastatin and resveratrol can inhibit endometriosis development ( Bahrami et al 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…Atorvastatin did not cause significant changes during the glucose tolerance test, but coadministration of atorvastatin and resveratrol suppressed glycolysis and neovascularization ( Bahrami et al 2021 ). The simultaneous administration of atorvastatin and resveratrol can inhibit endometriosis development ( Bahrami et al 2021 ). Gui-Zhi-Fu-Ling capsules, a classic Chinese medicinal formula, may have benefits in inhibiting endometriosis development through the suppression of the expression levels of TGF-β1, GLUT4, and VEGF in a rat endometriosis model ( Zhou et al 2018 ).…”

Section: Resultsmentioning

confidence: 99%

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Nonhormonal therapy for endometriosis based on energy metabolism regulation

Kobayashi

Shinmoto

Imanaka

2021

Reproduction and Fertility

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Objectives: Ovarian function suppression is the current pharmacotherapy of endometriosis with limited benefit and adverse effects. New therapeutic strategies other than hormonal therapy are developed based on the molecular mechanisms involved in the hypoxic and oxidative stress environments and metabolism unique to endometriosis. Methods: A literature search was performed between January 2000 and March 2021 in the PubMed database using a combination of specific terms. Results: Endometriosis-associated metabolic changes have been organized into four hallmarks: (1) glucose uptake, (2) aerobic glycolysis, (3) lactate production and accumulation, and (4) metabolic conversion from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Endometriotic cells favor glycolytic metabolism over mitochondrial OXPHOS to produce essential energy for cell survival. Hypoxia, a common feature of the endometriosis environment, is a key player in this metabolic conversion, which may lead to glucose transporter overexpression, pyruvate dehydrogenase kinase 1 (PDK1) and lactate dehydrogenase kinase A (LDHA) activation, and pyruvate dehydrogenase complex inactivation. Evading mitochondrial OXPHOS mitigates excessive generation of reactive oxygen species (ROS) that may trigger cell death. Therefore, the coinactivation of LDHA and PDK1 can induce the accumulation of mitochondrial ROS by converting energy metabolism to mitochondrial OXPHOS, causing endometriotic cell death. Conclusion: Metabolic pattern reconstruction in endometriotic lesions is a critical factor in cell survival and disease progression. One therapeutic strategy that may avoid hormone manipulation is focused on mitigating metabolic changes that have been detected in cells/tissues from women with endometriosis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Nonhormonal therapy for endometriosis based on energy metabolism regulation

Kobayashi

Shinmoto

Imanaka

2021

Reproduction and Fertility

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“…TNF‐α decrease was however not achieved with 10 mg/Kg/d (Ergenoǧlu et al, 2013). Seven studies evidenced antiangiogenic properties for resveratrol; 40 mg/kg for 28 days significantly decreased proliferation of CD31‐positive endothelial cells in the newly developing microvasculature of the lesions and reduced MVD when compared with controls (Rudzitis‐Auth et al, 2013)(Bahrami et al, 2021). Treatment with resveratrol (10 and 25 mg/kg/day, intraperitoneally for 4 weeks), besides reducing cell proliferation and increasing apoptosis within the lesions, also reduced vascular density, despite the absence of effect on peritoneal VEGF levels (Ricci et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Impact of curcumin, quercetin, or resveratrol on the pathophysiology of endometriosis: A systematic review

Hipólito-Reis

Neto

Neves

2022

Phytotherapy Research

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Endometriosis, a gynecological disease that affects reproductive age women is difficultly controlled in the long term by currently available treatments, prompting patients to adopt self-controlled interventions including dietary changes. The aim of this review is to provide evidence of how curcumin, quercetin, and resveratrol can act as natural interventions to control endometriosis. The review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was carried out in PubMed, Scopus, and Web of Science to gather together all the articles that study the specific actions of curcumin, resveratrol, or quercetin in endometriosis pathophysiology. All types of study designs including experimental data were considered. Thirty articles, including a clinical trial, were included. For the assessment of the quality of the selected studies that globally have "good quality", the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and the SYRCLE ROB tool criteria were used. By acting on mechanisms of inflammation, oxidative stress, cell proliferation, invasion and adhesion, apoptosis, angiogenesis and glucose and lipid metabolism, curcumin, quercetin, and resveratrol showed to have beneficial effects, evidencing their potential application in the endometriosis treatment. However, future clinical studies are necessary to determine the real efficacy of these compounds in human endometriosis.

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“…At least 5 studies on resveratrol were performed using the rat autotransplant model. Yavuz et al observed that resveratrol (1 mg/kg/day and 10 mg/kg/day) intraperitoneal injection for 7 days was able to reduce the volumes as well as the histological scores of the implants [71]; Ergenoglu et al observed that following muscle injection of resveratrol (10 mg/kg/day) for 14 days inhibited the vascular endothelial growth factor (VEGF) expression in the peritoneal fluid/plasma and MCP-1 expression in the peritoneal fluid, and reduced the size of implant [72]; Tekin et al observed that muscle injection of resveratrol (30 mg/kg/day) for 14 days reduced the volumes, histopathological grades, and VEGF expression in the implants, and IL-6, IL-8 and TNF-α in the peritoneal fluid [73]; Cenksoy et al reported that oral administration of resveratrol (60 mg/kg/day) for 21 days led to reduced lesion areas, histopathological grades, and VEGF staining scores of the implants, and reduced VEGF and MCP-1 levels in peritoneal fluid [74]; Bahrami et al investigated the therapeutic effects of resveratrol and the LDL reduction reagent atorvastatin on the expression of glucose transporters 1 and 3 (GLUT-1 and GLUT-3), monocarboxylate trans-porters 1 and 4, and neovascularization in the implants [75]. The results showed that resveratrol (40 mg/kg/day) for 28 days alone or in combination with atorvastatin were able to reduce the size and vascularization as well as the expression of tested genes in the implants.…”

Section: Findings From Rodent Study Modelsmentioning

confidence: 99%

Phytoestrogens for the Management of Endometriosis: Findings and Issues

et al. 2021

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Endometriosis, a chronic disease characterized by recurrent pelvic pain and infertility, severely impacts the health and life quality of many women worldwide. Since phytoestrogens are commonly found in a variety of foods, and estrogen is a major pathological factor for the pathogenesis of endometriosis, their possible involvement cannot be ignored. This review summarizes data on the relationship between phytoestrogen intake and endometriosis risk, and analyzes the findings from in vitro experiments, rodent endometriotic models, and human intervention trials. While favorable results were often obtained from endometrial primary cultures and animal models for resveratrol, isoflavones and puerarin, only resveratrol showed promising results in human intervention trials. Critical issues concerning the current study efforts are discussed: the possible reasons beneath the discrepant observations of estrogenic/anti-estrogenic effects by phytoestrogens; the complicated interplays between phytoestrogens and endogenous estrogens; the shortage of currently used animal models; the necessity to apply reasonable doses of phytoestrogens in experiments. It is expected that the analyses would help to more properly assess the phytoestrogens’ effects on the endometriosis pathogenesis and their potential values for preventive or therapeutic applications.

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Effects of atorvastatin and resveratrol against the experimental endometriosis; evidence for glucose and monocarboxylate transporters, neoangiogenesis

Cited by 18 publications

References 47 publications

Nonhormonal therapy for endometriosis based on energy metabolism regulation

Nonhormonal therapy for endometriosis based on energy metabolism regulation

Impact of curcumin, quercetin, or resveratrol on the pathophysiology of endometriosis: A systematic review

Phytoestrogens for the Management of Endometriosis: Findings and Issues

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