Effectiveness of N-Acetylcysteine in the Treatment of Renal Deterioration Caused by Long-Term Exposure to Bisphenol A

Abstract

Human health hazards caused by bisphenol A (BPA), a precursor for epoxy resins and polycarbonate-based plastics, are well documented and are closely associated with mitochondrial impairment and oxidative imbalance. This study aimed to assess the therapeutic efficacy of N-acetylcysteine (NAC) on renal deterioration caused by long-term BPA exposure and examine the signaling transduction pathway involved. Male Wistar rats were given vehicle or BPA orally for 12 weeks then the BPA-treated group was subdivided to receive vehicle or NAC concurrently with BPA for a further 4 weeks, while the vehicle-treated normal control group continued to receive vehicle through to the end of experiment. Proteinuria, azotemia, glomerular filtration reduction and histopathological abnormalities caused by chronic BPA exposure were significantly reduced following NAC therapy. NAC also diminished nitric oxide and lipid peroxidation but enhanced renal glutathione levels, and counteracted BPA-induced mitochondrial swelling, increased mitochondrial reactive oxygen species production, and the loss of mitochondrial membrane potential. The benefit of NAC was related to the modulation of signaling proteins in the AMPK-SIRT3-SOD2 axis. The present study shows the potential of NAC to restore mitochondrial integrity and oxidative balance after long-term BPA exposure, and suggests that NAC therapy is an effective approach to tackle renal deterioration in this condition.

Impact of Bisphenol A on Structure and Function of Mitochondria: A Critical Review

“…Male Wistar rats exposed to BPA showed mitochondrial swelling and increased ROS production in the renal tissue (Kobroob et al 2021). NAC treatment restored mitochondrial integrity and oxidative balance by modulating the AMPK-SIRT3-SOD2 axis (Kobroob et al 2021). Thus, NAC can be used to prevent the renal toxicities caused due to long-term exposure to BPA.…”

“…In rat liver, quercetin protects against BPA-induced mitochondrial toxicity (Mahdavinia et al 2019). N-Acetyl Cysteine (NAC) is a powerful antioxidant extensively used to relieve oxidative stress (Kobroob et al 2021). Male Wistar rats exposed to BPA showed mitochondrial swelling and increased ROS production in the renal tissue (Kobroob et al 2021).…”

“…N-Acetyl Cysteine (NAC) is a powerful antioxidant extensively used to relieve oxidative stress (Kobroob et al 2021). Male Wistar rats exposed to BPA showed mitochondrial swelling and increased ROS production in the renal tissue (Kobroob et al 2021). NAC treatment restored mitochondrial integrity and oxidative balance by modulating the AMPK-SIRT3-SOD2 axis (Kobroob et al 2021).…”

N-Acetyl-L-cysteine in human rheumatoid arthritis and its effects on nitric oxide (NO) and malondialdehyde (MDA): analytical and clinical considerations

“…Intravenous administration of 600 mg (3.7 mmol) NAC resulted in plasma concentrations of about 300 µM with a mean elimination half-life of 2.3 h (Borgström et al 1986). Even at high oral doses (≥ 600 mg/ day), NAC is considered pharmacologically safe (Calverley et al 2021;Kobroob et al 2021). The oral bioavailability of NAC is very low (6-10%) in humans (Borgström et al 1986;Holdiness 1991;Tenório et al 2021).…”

New Evidence of Renal and Cardiovascular Alterations Promoted by Bisphenol A

“…Firstly, in Kobroob et al [ 21 ], the authors verified that the kidney damage induced by BPA may be related to oxidative stress, and the administration of an antioxidant such as N-acetyl cysteine (NAC) is capable of restoring mitochondrial integrity and oxidative balance. Interestingly, the authors used a relatively low dose, since the 50 mg/kg dose has been considered no observable effect level (NOEL) in the renal system [ 22 , 23 , 24 ].…”