TNF-α antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats

Şahin, Tuğçe Demirtaş; Yazır, Yusufhan; Utkan, Tijen; Gacar, Gülçin; Rençber, Selenay Furat; Göçmez, S.S.

doi:10.1139/cjpp-2017-0113

Cited by 19 publications

(7 citation statements)

References 46 publications

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“…Briefly, in an animal model of hypogonadism, where there are reduced testosterone levels, inflammatory cytokines such as IL-6, IL-1β, and TNF-α were said to be elevated and only IL-6 was reduced after testosterone treatment [ 81 , 82 ]. Similarly, findings from human studies have also shown that there are increased inflammatory cytokines in hypogonadism [ 83 , 84 ].…”

Section: Mechanisms Through Which Statins May Impact Male Reproductionmentioning

confidence: 99%

Statins and Male Fertility: Is There a Cause for Concern?

Omolaoye

Halabi

Mubarak

et al. 2022

Toxics

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The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia and some cases of cardiovascular diseases. The effectiveness of this drug in controlling cholesterol production is impeccable, however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis. Not only has the use of statins caused the aforementioned side effects, but they are also shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production. These reported adverse effects on male fertility are not generally agreed upon, as some have shown the use to be beneficial. Hence, this makes the aftermath effect of statin use on male fertility debatable and controversial. The negative effects have been associated with imbalanced or reduced steroid hormones, which are necessary for proper spermatogenesis and other sexual functions. Meanwhile, the beneficial effects are related to statin’s anti-inflammatory and cardioprotective properties. These contradictory findings are in part due to the different age of users, concentrations of statins, the type and duration of treatment, and the underlying disease and/or comorbidities. Therefore, the current study aims to analyze the literature and gather evidence as to the effects of statin on male sexual health and reproductive parameters, and subsequently give recommendations for the direction of future studies.

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Section: Mechanisms Through Which Statins May Impact Male Reproductionmentioning

confidence: 99%

Statins and Male Fertility: Is There a Cause for Concern?

Omolaoye

Halabi

Mubarak

et al. 2022

Toxics

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“…found sex hormones in mice regulates visceral adipose tissue inflammation via shaping the transcriptional landscape of Treg cells in a BLIMP1 transcription factor-dependent manner (25). Aged rats treated with etanercept (a TNF-a inhibitor) showed obviously higher inflammatory markers while decreased serum testosterone (26). In induced colitis mouse model, E2 could inhibit inflammatory cytokines to produce an antiinflammatory effect through the estrogen receptor b signaling pathway (27).…”

Section: Introductionmentioning

confidence: 99%

The Association Between Dietary Inflammatory Potential and Sex Hormones in Male Children and Adolescents Aged 6–19 Years

et al. 2021

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AimsThis study aimed to assess the relationship between dietary inflammatory index (DII) and sex hormones in male children and adolescents aged 6-19 years.MethodsWe obtained data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Male participants aged 6-19 years old with the complete data of DII and sex hormones were included. Weighted multiple regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII and sex hormones.ResultsA total of 1717 male participants with the average age of 13.02 ± 3.82 years were enrolled, of whom 41.3% (n=713) were children and 58.47% (n=1004) were adolescents. In children, mean DII was 0.18 ± 1.67, with scores ranging from -4.53 to 4.08. As for adolescents, the mean DII was 0.36 ± 1.98, mean total testosterone (TT) was 376.94 ± 206.69 ng/dl overall. A negative association between DII with TT and estradiol (E2) was observed (TT: β=-11.97, P=0.0006; E2: β=-0.45, P=0.0108) in male adolescent. Subgroup analysis and interaction test results indicated that this association was similar in male adolescents with different body mass index. No statistically significant association was observed in children.ConclusionsPro-inflammatory diet was associated with lower TT and E2 level in male adolescent, while no association with statistical significance between them was observed in male children. However, more studies are still needed to validate the causal relationship between DII and sex hormones.

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“…Human recombinant interleukin-37 (IL-37), an anti-inflammatory cytokine of the interleukin-1 family, has been reported to favor vascular endothelial function in old age by increasing NO bioavailability and the phosphorylation of AMP-activated kinase (AMPK), as well as reducing levels of ROS [ 220 ]. Etanercept (TNF-α antagonism) treatment has been demonstrated to be useful to improve aging-impaired endothelium-dependent relaxant responses in rats [ 221 ]. Akt activation stimulates eNOS phosphorylation, increases NO production, and reduces oxidative stress [ 222 ].…”

Section: New Therapeutic Approaches Targeted Endothelial Dysfunctimentioning

confidence: 99%

Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets

Scioli

Storti

D’Amico

et al. 2020

JCM

127

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Cardiovascular diseases (CVD), including heart and pathological circulatory conditions, are the world’s leading cause of mortality and morbidity. Endothelial dysfunction involved in CVD pathogenesis is a trigger, or consequence, of oxidative stress and inflammation. Endothelial dysfunction is defined as a diminished production/availability of nitric oxide, with or without an imbalance between endothelium-derived contracting, and relaxing factors associated with a pro-inflammatory and prothrombotic status. Endothelial dysfunction-induced phenotypic changes include up-regulated expression of adhesion molecules and increased chemokine secretion, leukocyte adherence, cell permeability, low-density lipoprotein oxidation, platelet activation, and vascular smooth muscle cell proliferation and migration. Inflammation-induced oxidative stress results in an increased accumulation of reactive oxygen species (ROS), mainly derived from mitochondria. Excessive ROS production causes oxidation of macromolecules inducing cell apoptosis mediated by cytochrome-c release. Oxidation of mitochondrial cardiolipin loosens cytochrome-c binding, thus, favoring its cytosolic release and activation of the apoptotic cascade. Oxidative stress increases vascular permeability, promotes leukocyte adhesion, and induces alterations in endothelial signal transduction and redox-regulated transcription factors. Identification of new endothelial dysfunction-related oxidative stress markers represents a research goal for better prevention and therapy of CVD. New-generation therapeutic approaches based on carriers, gene therapy, cardiolipin stabilizer, and enzyme inhibitors have proved useful in clinical practice to counteract endothelial dysfunction. Experimental studies are in continuous development to discover new personalized treatments. Gene regulatory mechanisms, implicated in endothelial dysfunction, represent potential new targets for developing drugs able to prevent and counteract CVD-related endothelial dysfunction. Nevertheless, many challenges remain to overcome before these technologies and personalized therapeutic strategies can be used in CVD management.

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TNF-α antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats

Cited by 19 publications

References 46 publications

Statins and Male Fertility: Is There a Cause for Concern?

Statins and Male Fertility: Is There a Cause for Concern?

The Association Between Dietary Inflammatory Potential and Sex Hormones in Male Children and Adolescents Aged 6–19 Years

Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets

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