Spironolactone inhibits production of proinflammatory mediators in response to lipopolysaccharideviainactivation of nuclear factor-κB

Abstract

The effect of spironolactone (SPIR) on lipopolysaccharide (LPS)-induced production of proinflammatory mediators was examined using RAW 264.7 macrophage-like cells and mouse peritoneal macrophages. SPIR significantly inhibited LPS-induced production of nitric oxide (NO), tumor necrosis factor-α and prostaglandin E2. The inhibition was not mediated by cell death. SPIR reduced the expression of an inducible NO synthase mRNA in response to LPS. SPIR significantly inhibited phosphorylation of p65 nuclear factor (NF)-κB in response to LPS. Furthermore, SPIR inhibited phosphorylation of IκB kinase (IKK) as an upstream molecule of NF-κB in response to LPS. LPS did not induce the production of aldosterone in RAW 264.7 cells. Taken together, SPIR is suggested to inhibit LPS-induced proinflammatory mediators via inactivation of IKK/NF-κB in LPS signaling.

Beneficial Effects of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Cases

“…Other anti-inflammatory agents beyond those already discussed have been studied in autism. Spironolactone is a potassium sparing diuretic and an anti-inflammatory which downregulates nuclear factor- κ B [ 24 ]. Bradstreet et al reported the first case of significant reduction in autism severity and improved expressive language after a short course of spironolactone [ 25 ].…”

Effects of mineralocorticoid receptor antagonists on responses to hemorrhagic shock in rats

“…MR antagonists are often used to treat hypertensive patients and have beneficial effects in patients with chronic heart failure and ischemic heart diseases[ 14 , 15 , 22 , 23 ]. Many recent investigations have demonstrated the beneficial effects of MR antagonists with respect to inflammatory responses and IRI in vitro and in vivo [ 6 - 13 ]. Kato et al[ 6 ] showed that SPL inhibits the production of pro-inflammatory mediators, such as TNF-α and nitric oxide, in response to lipopolysaccharides in vitro .…”

“…Ischemic and reperfusion injury (IRI) causes the release of numerous pro-inflammatory mediators, such as cytokines and nitric oxide, and results in multiple organ dysfunction (MOD), a leading cause of death in HS patients[ 1 - 5 ]. Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPL) and eplerenone (EP), have anti-inflammatory effects in vitro [ 6 - 8 ]. In particular, SPL inhibits inflammatory responses, such as the attenuation of cytokine and NF-kappa B responses, in vitro [ 6 - 8 ].…”

“…Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPL) and eplerenone (EP), have anti-inflammatory effects in vitro [ 6 - 8 ]. In particular, SPL inhibits inflammatory responses, such as the attenuation of cytokine and NF-kappa B responses, in vitro [ 6 - 8 ]. Moreover, in several animal models, MR antagonists protect against IRI in various organs, including the kidney, liver, intestine, heart, and brain[ 9 - 13 ].…”

Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy

“…Spironolactone is a synthetic 17-lactone steroid, belonging to the "potassium-sparing diuretics" class of drugs and is known as a competitive aldosterone antagonist [76] with potent anti-inflammatory, immunologic, and hormone-modifying properties [77][78][79][80]. Currently, this drug has been used for acne, hirsutism, and precocious puberty, demonstrating safety and tolerability.…”