Abstract
Mitochondrial impairment ensuing from oxidative imbalance is related to adverse consequences of bisphenol A (BPA), a globally utilized industrial chemical. Recent evidence reveals sirtuin 3 (SIRT3) as a key regulator of mitochondrial homeostasis; however, its role in BPA toxicity remains unidentified. This study explored the potential benefits of N-acetylcysteine (NAC), an effective antioxidant, against BPA toxicity in the kidney and liver, and examined whether SIRT3 was involved in this condition. Male Wistar rats were fed with vehicle, BPA (5, 50 mg/kg), BPA (50 mg/kg) plus NAC (100 mg/kg) and were evaluated after 5 weeks. NAC treatment significantly diminished BPA-induced kidney and liver functional disorders, histopathological alterations, oxidative stress, and apoptosis. The increased mitochondrial reactive oxygen species, the disrupted membrane potential, the swelling, and the impaired mitochondrial fission caused by BPA were also mitigated upon concurrent treatment with NAC. The benefits of NAC were associated with enhanced AMPK-PGC-1α-SIRT3 signaling protein expressions, which led to decreased acetylation of superoxide dismutase 2 (SOD2) and increased expression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD). The findings demonstrate the efficacy of NAC in protecting BPA-induced kidney and liver injury, which, in part, is mediated by activating SIRT3 and improving mitochondrial function, dynamics, and oxidative imbalance.
Highlights
Bisphenol A (BPA), one of the most utilized industrial chemicals worldwide, is commonly found in a variety of consumer products, in those of polycarbonate plastics and epoxy resins [1]
Maintenance of homeostasis within the mitochondria and prevention of redox imbalance may be a promising therapeutic strategy to cope with these disorders, including the toxicity caused by BPA
The present study explored this issue with particular attention on the role of the silent information regulator T3 or sirtuin 3 (SIRT3) as this signaling molecule has recently been highlighted as playing an important role in the regulation of redox balance and mitochondrial homeostasis [13]
Summary
Bisphenol A (BPA), one of the most utilized industrial chemicals worldwide, is commonly found in a variety of consumer products, in those of polycarbonate plastics and epoxy resins [1]. Several lines of evidence from epidemiological and experimental studies pointed towards the adverse health effects of BPA in multiple organ systems [4,5,6]. These unfavorable outcomes induced by BPA have been demonstrated to be associated with oxidative stress and disorders of the mitochondria [4,5]. In the past few years, the mitochondrial protection by NAC has been demonstrated in several in vivo and in vitro study models [9,10,11], including BPA-induced neurotoxicity [12]. How NAC protects the mitochondria and the mechanisms responsible for its actions are as yet unknown
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