Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model

Abstract

Background of study Globally, many reproductive aged women are affected by polycystic ovarian syndrome (PCOS), which is a common endocrine and metabolic disorder that is linked with adipose dysfunction and chronic low-grade inflammation. Spironolactone (SPL), a mineralocorticoid receptor blocker has been documented as a metabolic modulator. However, its immunomodulatory effect in PCOS is unknown. Therefore, the present study hypothesized that SPL would ameliorate adipose dysfunction and inflammation in experimental PCOS animals. Materials and methods Female Wistar rats that were 8 weeks old were allocated into three groups. Group 1 received vehicle (distilled water; p.o.), group 2 received letrozole (1 mg/kg; p.o.) and group 3 received letrozole plus SPL (0.25 mg/kg, p.o.). The administration was performed once daily for 21 days. Results The experimental PCOS animals showed insulin resistance, hyperinsulinemia and hyperandrogenism as well as oxidative stress and elevated inflammatory biomarkers (NF-kB/TNF-/IL-6) as well as a significant decrease in triglycerides, total cholesterol, free fatty acids, GSH and G6PD in the adipose tissue of PCOS animals. In addition, immunohistochemical assessment of adipose tissue showed significant expression of BAX and inflammasome, indicating apoptosis and inflammation compared to control animals. Nevertheless, administration of SPL attenuated these perturbations. Conclusion Altogether, the present study suggests that low-dose spironolactone confers protection against adipose dysfunction in experimental PCOS animals by attenuating inflammation, oxidative stress and cellular apoptosis.

Protective effects of vanillic acid on letrozole-induced polycystic ovarian syndrome: A comprehensive study in female wistar rats

“…Earlier studies suggested that chronic oxidative stress results in inflammatory process, tissue remodeling and apoptosis ( Ye et al, 2023 ). LET n the earlier studies have increased the markers of inflammation and apoptosis, suggesting its mechanism in PCOS ( Areloegbe et al, 2022 ). Besides, the treatments that have promising effects in PCOS are found to reduce these markers such as NF-kB, TNF-α, and interleukin-6 ( Ji et al, 2023 ).…”

Lactiplantibacillus plantarum attenuates Coxsackievirus B3-induced pancreatitis through the BAX/BCL2/CASP3 signaling pathway

“…6 Altogether, CVB3 infection might result in the recruitment of neutrophils and macrophages into the pancreatic tissue, aggravating the inflammatory process and leading to cellular apoptosis. 38 LAB has several health benefits, including improving intestinal microbiota, 39 regulating immune function, and antitumor and antiviral effects. L. plantarum , one of the most common LAB, also positively influences the host.…”

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

“…In a study in rats, the use of spironolactone as a metabolic modulator was associated with protection against lipid dysfunction (Areloegbe et al., 2022 ) and in an experimental study, the use of spironolactone with mineralocorticoid antagonistic effects compared to the control group was associated with a significant reduction in body mass loss following starvation only in the first week of use, while this effect was not different from the control group in the following weeks (Pfalzgraff & Skov, 2022 ).…”