Eplerenone Attenuates Fibrosis in the Contralateral Kidney of UUO Rats by Preventing Macrophage-to-Myofibroblast Transition

Xiong, Yan; Chang, Yi; Hao, Juan; Zhang, Cuijuan; Yang, Fan; Wang, Zheng; Liu, Yunmeng; Wang, Xiangting; Mu, Shengyu; Xu, Qingyou

doi:10.3389/fphar.2021.620433

Cited by 24 publications

(30 citation statements)

References 26 publications

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“…Eplerenone inhibits inflammation (macrophage and monocyte infiltration) and fibrosis (by reducing the level of IL-1β), reduces oxidative stress, and promotes alternative activation in macrophages [ 116 , 117 , 118 , 119 ]. Eplerenone has a beneficial effect in patients with metabolic syndrome, as it prevents excessive weight gain and fat storage and improves glucose intolerance and insulin resistance.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…Inflammation (macrophage and monocyte infiltration), fibrosis (by reducing the level of IL-1β), and oxidative stress [ 116 , 117 , 118 , 119 ];…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Potential of Diuretics

Bryniarski

Nazimek

Marcinkiewicz

2021

Biology

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“…Obstructive kidney disease is one of the primary causes of kidney damage and leads to kidney failure (24). UUO is a classic model used to study obstructive kidney disease and renal fibrosis (25)(26)(27). In 180-day UUO rats, UUO caused kidney injury and systemic blood pressure changes.…”

Section: Discussionmentioning

confidence: 99%

Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis

Liu¹,

Zhang²,

Hao

et al. 2022

Exp Ther Med

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Chronic kidney disease (CKD) involves progressive and irreversible loss of renal function, often causing complications and comorbidities and impairing the function of various organs. In particular, lung injury is observed not only in advanced CKD but also in early-stage CKD. The present study investigated the potential involvement of mineralocorticoid receptors (MRs) and lymphatic vessels in lung injury using a 180-day unilateral ureteral obstruction (UUO) model for CKD. Changes in lung associated with lymphangiogenesis and inflammatory were analyzed in UUO rats. The pathology of the lung tissue was observed by hematoxylin and eosin and Masson's staining. Detection of the expression of lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), Podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3) and VEGF C to investigate lymphangiogenesis. The mRNA and protein expression levels of IL-1β, monocyte chemotactic protein 1, tumor necrosis factor-α, nuclear factor κB, phosphorylated serum and glucocorticoid-induced protein kinase-1 and MR were evaluated using western blot, reverse transcription-quantitative PCR, immunohistochemical staining and immunofluorescence staining. In the present study, long-term UUO caused kidney damage, which also led to lung inflammation, accompanied by lymphangiogenesis. However, treatment with eplerenone, an MR blocker, significantly reduced the severity of lung injury and lymphangiogenesis. Therefore, lymphangiogenesis contributed to lung fibrosis in UUO rats due to activation of MRs. In addition, transdifferentiation of lymphatic epithelial cells into myofibroblasts may also be involved in lung fibrosis. Collectively, these findings provided a potential mechanism for lung fibrosis in CKD and suggested that the use of eplerenone decreased kidney damage and lung fibrosis.

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“…Moreover, it also attenuated the fibrosis that develops in the contralateral kidney of UUO rats via inhibition of the macrophage to myofibroblast transition. (Xiong et al, 2021) In a rat model of polycystic kidney disease (PKD), spironolactone treatment attenuated hypertension in female rats only. Spironolactone reduced albuminuria and plasma creatinine, but fibrosis and cyst size were not modified.…”

Section: Mr Antagonism Alleviates Kidney Injury In Various Pre-clinic...mentioning

confidence: 99%

“…In rats with UUO, eplerenone inhibited renal fibrosis and inflammation and reduced monocyte and macrophage infiltration, interstitial cell proliferation and oxidative stress (Chen et al, 2013). Moreover, it also attenuated the fibrosis that develops in the contralateral kidney of UUO rats via inhibition of the macrophage to myofibroblast transition (Xiong et al, 2021).…”

Section: The Mr and Ckd Without Diabetesmentioning

confidence: 99%

The mineralocorticoid receptor in chronic kidney disease

Barrera‐Chimal

Jaisser

Anders

2021

British J Pharmacology

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Chronic kidney disease (CKD) is a major public health concern, affecting approximately 10% of the population worldwide. CKD of glomerular or tubular origin leads to the activation of stress mechanisms, including the renin angiotensin aldosterone system and mineralocorticoid receptor (MR) activation. Over the last two decades, blockade of the MR has arisen as a potential therapeutic approach against various forms of kidney disease.In this review, we summarize the experimental studies that have shown a protective effect of MR antagonists (MRAs) in non-diabetic and diabetic CKD animal models. Moreover, we review the main clinical trials that have shown the clinical application of MRAs to reduce albuminuria and, importantly, to slow CKD progression. Recent evidence from the FIDELIO trial showed that the MRA finerenone can reduce hard kidney outcomes when added to the standard of care in CKD associated with type 2 diabetes. Finally, we discuss the effects of MRAs relative to those of SGLT2 inhibitors, as well as the potential benefit of combination therapy to maximize organ protection.

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Eplerenone Attenuates Fibrosis in the Contralateral Kidney of UUO Rats by Preventing Macrophage-to-Myofibroblast Transition

Cited by 24 publications

References 26 publications

Immunomodulatory Potential of Diuretics

Immunomodulatory Potential of Diuretics

Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis

The mineralocorticoid receptor in chronic kidney disease

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