17β-Estradiol protects against lung injuries after brain death in male rats

Vieira, Roberta Figueiredo; Breithaupt‐Faloppa, Ana Cristina; Matsubara, Bruno Carvalho; Rodrigues, Geovana; Sanches, Marcelo Petrof; Armstrong‐Jr, Roberto; Ferreira, Sueli Gomes; Correia, Cristiano de Jesus; Moreira, Luíz Felipe Pinho; Sannomiya, Paulina

doi:10.1016/j.healun.2018.06.015

Cited by 17 publications

(13 citation statements)

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“…After activation of inflammatory process in the lungs, alveolar macrophages, and neutrophils express iNOS and produce large amounts of NO, thus, resulting in tissue injury [30]. Previous work from our group reported that iNOS accumulated significantly in inflammatory cells in the lung parenchyma after brain death in male rats [31]. Here, we showed that BD non-OVx rats presented higher iNOS protein expression in comparison to control.…”

Section: Discussionsupporting

confidence: 53%

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

et al. 2019

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Summary Organ donor's age negatively influences graft survival of organs, increasing risk of complications. Aging occurs in both men and women; however, the menopause marks a decrease in sex hormones and a sudden increase in the process of vascular aging. We investigated sex hormones' influence on the lung inflammatory process induced by BD in female rats. Wistar rats were grouped as: female rats from high estradiol to heat period (non‐OVx) and ovariectomized (OVx) female rats. Ovariectomy was carried out 10 days before BD. BD was induced using intracranial balloon rapid inflation. Serum hormones and inflammatory mediators were quantified, leukocytes and platelets counted and lung samples were collected for RT‐PCR, immunohistochemical, and histological analysis. Female sex hormones and corticosterone were reduced 6 h after BD in non‐OVx group. The infiltration of leukocytes in female non‐OVx lungs was higher compared to OVx. G‐CSF, VEGF, and CINC‐1 were found increased in non‐OVx group serum in comparison to OVx. Lung mediators were increased in non‐OVx rats compared to controls. The acute reduction of sex hormones induced by BD appears to have a worse effect on lung inflammation than a reduction that has happened over a prolonged period of time, allowing a physiological adaptation prior to BD.

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Section: Discussionsupporting

confidence: 53%

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

et al. 2019

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“…Unlike in the BD group, 17β‐estradiol‐treated rats did not develop leukocytosis after 6 h of BD induction. However, estradiol treatment did not result in significant changes in the levels of systemic cytokines, despite the observation of this influence in male animals [12].…”

Section: Discussionmentioning

confidence: 99%

Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

et al. 2020

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The viability of donor organs is reduced by hemodynamic and immunologic alterations caused by brain death (BD). Female rats show higher heart inflammation associated with the reduction in female sex hormones after BD. This study investigated the effect of 17b-estradiol (E2) on BD-induced cardiac damage in female rats. Groups of female Wistar rats were assigned: Sham-operation (Sham), brain death (BD), treatment with E2 (50 lg/ml, 2 ml/h) 3 h after BD (E2-T3), or immediately after BD confirmation (E2-T0). White blood cell (WBC) count was analyzed; cytokines and troponin-I were quantified. Heart histopathological changes and expression of endothelial nitric oxide synthase, endothelin-1, intercellular adhesion molecule-1, BCL-2, and caspase-3 were evaluated. Cardiac function was continuously assessed for 6 h by left ventricular pressure-volume loop analysis. E2 decreased the BD-induced median serum concentration of troponin-I (BD:864.2 vs. E2-T0:401.4; P = 0.009), increased BCL-2 (BD:0.086 vs. E2-T0:0.158; P = 0.0278) and eNOS median expression in the cardiac tissue (BD:0.001 vs. E2-T0:0.03 and E2-T3:0.0175; P < 0.0001), and decreased caspase-3 (BD:0.025 vs. E2-T0:0.006 and E2-T3:0.019; P = 0.006), WBC counts, leukocyte infiltration, and hemorrhage. 17b-estradiol treatment was effective in reducing cardiac tissue damage in brain-dead female rats owing to its ability to reduce leukocyte infiltration and prevent cardiomyocyte apoptosis.

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“…Estrogens have demonstrated beneficial actions against viral infections and respiratory complications, as clinically observed by better outcomes in women during reproductive age [159,[247][248][249][250][251][252][253][254][255][256][257][258][259], due to their protective effect on endothelial function, vasodilation in the pulmonary vasculature, stimulation stimulate of the humoral response to viral infections [159,[247][248][249][250][251][252][253], and modulation of inflammatory responses [248,249], leading to improved outcomes in acute lung injuries of any etiology [254][255][256][257][258][259]. Estrogens favorably modulates the RAAS in females [260][261][262], whereas the androgenmediated TMPRSS2 expression has dual correlation with estrogens [248,263,264].…”

Section: Of Minor Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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17β-Estradiol protects against lung injuries after brain death in male rats

Cited by 17 publications

References 34 publications

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

Repurposing existing drugs for COVID-19: an endocrinology perspective

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