Targeting p-AKT/mTOR/MAP kinase signaling, NLRP3 inflammasome and apoptosis by fluvastatin with or without taxifolin mitigates gonadal dysfunction induced by bisphenol-A in male rats

Abstract

Bisphenol-A (BPA) is a chemical substance that is widely used in industry for manufacturing of plastic bottles and resins. Recent reports found that BPA may mimic the effects of estrogen to a great manner that might disrupt the normal hormonal balance in the human body. Fluvastatin is an agent used for treatment of hypercholesterolemia that was proven to possess promising antioxidant ant anti-inflammatory properties. Taxifolin is a polyphenolic compound with potential antioxidant and antiestrogenic effects. The present study investigated the prospect of fluvastatin with or without taxifolin to mitigate testicular dysfunction elicited by BPA in rats. In a model of BPA-induced testicular toxicity, the hormonal profile was assessed and the testicular tissues were examined by biochemical analysis, histopathology, and immunohistochemistry. Fluvastatin with or without taxifolin improved the body weight gain, hormonal profile, testicular weight and functions, sperm characteristics, the antioxidant status, and the anti-inflammatory mechanisms together with enhancement of autophagy and suppression of the proapoptotic events induced by BPA in the testicular tissues. In addition, fluvastatin with or without taxifolin significantly mitigated the histopathological and the immunohistochemical changes induced by BPA in the testicular tissues. These desirable effects were more pronounced with fluvastatin/taxifolin combination relative to the use of each of these agents alone. In tandem, fluvastatin/taxifolin combination might counteract the pathogenic events induced by BPA in the testicular tissues which may be considered as a novel strategy for amelioration of these disorders.

Melatonin alleviates oxidative stress damage in mouse testes induced by bisphenol A

“…It has been clinically used for the treatment of autism ( Lalanne et al, 2021 ), Alzheimer’s disease ( Sumsuzzman et al, 2021 ), and endometriosis ( Li et al, 2022 ). BPA is a commonly encountered endocrine disruptor in humans, which can cause oxidative stress damage in testicular tissues, leading to hormonal changes, reduced testicular weight, and impaired sperm production in mice ( Behmanesh et al, 2018 ; Kabel et al, 2022 ). The use of antioxidants to alleviate testicular oxidative stress damage caused by BPA is an important measure for protecting the normal development of testicular cells.…”

Deciphering the molecular mechanism of NLRP3 in BPA-mediated toxicity: Implications for targeted therapies

“… Increased Nrf-2, TLR4, and NLRP3 inflammasome expression. Elevated levels of IL-8, IL-18, and TGF-β1 Wistar rats [ 121 ] BPA 10–100 nM Inflammasome activity Increased ER-α, IFN-β mRNAs, and NLRP3 Murine Bone marrow-derived cells [ 122 ] Elevated levels of STAT1, Caspase-1, IL-1β [(NZB × NZW) F 1 ], Female C57BL/6J (B6) mice Increased in level of IRF5, IL-18, NLRP3, STAT1, Procaspase-1 and activate STAT-1. Increase in AIM2 protein in mononuclear cells.…”