A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes

Lin, Mengyue; Heizati, Mulalibike; Wang, Lin; Nurula, Muyesaier; Yang, Zhen; Wang, Zhongrong; Abudoyreyimu, Reyila; Wu, Zihao

doi:10.1080/08037051.2021.1880881

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…The limitation of this study was that we focused only on IL‐6 cytokine, the clinical relevance requires further confirmation. Several other molecular mechanisms underlying GR agonist and MR antagonist analgesic effects are associated with various cytokines, including tumor necrosis factor‐α and IL‐1β 27,30–32 . However, an approach targeting IL‐6 has been applied in the treatment of various chronic inflammatory diseases 33 .…”

Section: Discussionmentioning

confidence: 99%

“…Several other molecular mechanisms underlying GR agonist and MR antagonist analgesic effects are associated with various cytokines, including tumor necrosis factor‐α and IL‐1β. 27 , 30 , 31 , 32 However, an approach targeting IL‐6 has been applied in the treatment of various chronic inflammatory diseases. 33 Therefore, further in‐depth elucidation of the regulation of IL‐6 signaling is of theoretical and clinical significance to pain management.…”

Section: Discussionmentioning

confidence: 99%

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Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Liu

Xie

et al. 2022

Immunity Inflam & Disease

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Background Dexamethasone (Dexa) and potassium canrenoate (Cane) modulate nociceptive behavior via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by two mechanisms (genomic and nongenomic pathways). This study was designed to investigate the Dexa‐ or Cane‐mediated nongenomic and genomic effects on mechanical nociception and inflammation‐induced changes in interleukin‐6 (IL‐6) mediated signaling pathway in rats. Methods Freund's complete adjuvant (FCA) was used to trigger an inflammation of the right hind paw in male Sprague–Dawley rats. First, the mechanical nociceptive behavioral changes were examined following intraplantar administration of GR agonist Dexa and/or MR antagonist Cane in vivo. Subsequently, the protein levels of IL‐6, IL‐6Rα, JAK2, pJAK2, STAT3, pSTAT3Ser727, migration inhibitory factor, and cyclooxygenase‐2 were assessed by Western blot following intraplantar injection of Dexa or Cane or the combination. Moreover, the molecular docking studies determined the interaction between Dexa, Cane, and IL‐6. The competition binding assay was carried out using enzyme‐linked immunosorbent assays (ELISA). Results Administration of Dexa and Cane dose‐dependently attenuated FCA‐induced inflammatory pain. The sub‐additive effect of Dexa/Cane combination was elucidated by isobologram analysis, accompanied by decrease in the spinal levels of IL‐6, pJAK2, and pSTAT3Ser727. The molecular docking study demonstrated that both Dexa and Cane displayed a firm interaction with THR138 binding site of IL‐6 via a strong hydrogen bond. ELISA revealed that Dexa has a higher affinity to IL‐6 than Cane. Conclusions There was no additive or negative effect of Dexa and Cane, and they modulate the IL‐6/JAK2/STAT3 signaling pathway through competitive binding with IL‐6 and relieves hypersensitivity during inflammatory pain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Liu

Xie

et al. 2022

Immunity Inflam & Disease

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“…Spironolactone inhibits the expression of iNOS in the skin and decreases the expression of matrix metallopeptidase 9, CCL-2, IL-1α and IL-1β, and the number of local pro-inflammatory M1 macrophages, resulting in an increase in the M2/M1 ratio in the wound microenvironment [ 107 ]. A previous meta-analysis proved that spironolactone reduces the markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP, and TNF-α [ 108 ]. In the TOPCAT Biorepository Study (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial), for patients with symptomatic heart failure (HF), ejection fraction (EF) ≥ 45%, and elevated natriuretic peptide levels or prior hospitalization for HF, spironolactone did not affect CRP levels [ 109 ].…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Potential of Diuretics

Bryniarski

Nazimek

Marcinkiewicz

2021

Biology

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In this review, diuretics and their immunomodulatory functions are described. The effects on the immune response of this group of drugs are reported in patients suffering from hypertension and under experimental conditions involving animal models and cell line studies. The pathogenesis of hypertension is strongly connected to chronic inflammation. The vast majority of diuretics modulate the immune response, changing it in favor of the anti-inflammatory response, but depending on the drug, these effects may differ. This topic is significantly important in medical practice regarding the treatment of patients who have coexisting diseases with chronic inflammatory pathogenesis, including hypertension or chronic heart failure. In patients with metabolic syndrome, allergies, or autoimmune disorders, the anti-inflammatory effect is favorable, because of the overstimulation of their immune system. Otherwise, in the geriatric population, it is important to find the proper anti- and pro-inflammatory balance to avoid an enhancement of immune response suppression, which can result in reducing the risk of serious infections that can occur due to the age-diminished function of the immune system. This article is intended to facilitate the selection of an antihypertensive drug that depends on the patient’s immune situation.

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“…Based on the studies conducted in patients with hypertension and diabetes, treatment with spironolactone is accompanied by a decrease in the serum levels of many inflammatory markers such as CRP and TNF‐α (Lin et al., 2021 ). Antioxidant effects of spironolactone have been reported in the form of reducing inflammatory and pro‐inflammatory processes (with markers such as decreasing levels of TNF‐α and interleukin 1 beta [IL‐1β]) (Velioğlu öğünç, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar‐I disorder: A double‐blind, randomized, placebo‐controlled clinical trial

Zandifar,

Badrfam,

Gholamian

et al. 2023

Brain and Behavior

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IntroductionTreatment of mood and cognitive symptoms of patients with bipolar disorder is associated with many complications and is generally not associated with therapeutic satisfaction. In this clinical trial, we evaluated the effectiveness of spironolactone in controlling mood and cognitive symptoms, sleep quality, appetite, and body mass index in patients with bipolar disorder in manic episodes.MethodsSixty inpatients with bipolar disorder in manic episodes were treated with spironolactone/placebo in an 8‐week randomized, double‐blind, placebo‐controlled clinical trial. They were evaluated using the Young Mania Rating Scale (YMRS), mini‐mental state examination (MMSE), Pittsburgh sleep quality index, Simplified Nutritional Appetite Questionnaire, and body mass index in weeks 1, 4, and 8.ResultsFor cognitive impairment (MMSE), there were significant interaction effects of group and time at week 8 (B = −1.60, SE = 0.69, t = −2.33, p = .021) such that individuals in the spironolactone group experienced more improvement in their cognitive performance. For manic symptoms (YMRS), there were no significant interaction effects of group and time at week 8 (B = −2.53, SE = 1.46, t = −1.73, p = .085).ConclusionsConsidering the promising findings in this clinical trial, further study of spironolactone as adjunctive therapy in bipolar disorder in manic episodes with larger sample sizes, multicenter settings, and longer follow‐ups are recommended.

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A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes

Cited by 10 publications

References 35 publications

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Immunomodulatory Potential of Diuretics

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar‐I disorder: A double‐blind, randomized, placebo‐controlled clinical trial

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