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Aims: Bisphenol A (BPA) can induce intestinal epithelial cell barrier dysfunction; however, its effects on the intestinal mucus barrier remain unclear. We used LS174T cells as a model to investigate the effects of BPA on the functions of intestinal goblet cells., Main Methods: This study used CCK-8, flow cytometry, ELISA and real-time PCR to investigate the effects of BPA on mitochondrial dynamics, oxidative stress and apoptosis in goblet cells. In addition, mucin synthesis and secretion were evaluated using PAS staining and a PAS assay, respectively., Key Findings: Our results indicate that BPA reduced cell viability in a time- and concentration-dependent manner. BPA induced mitochondrial dysfunction, as indicated by the depolarization of the mitochondrial membrane potential, inhibition of mitochondrial respiratory chain complex enzyme activity and reduction of ATP production. Moreover, BPA caused oxidative stress by significantly increasing the accumulation of ROS, as well as oxidative stress products, and reducing the antioxidant capacity. Furthermore, BPA induced intestinal goblet cell apoptosis, accompanied by increased DNA fragmentation, caspase-3, -8, -9,-10 gene expression and enzyme activity. Additionally, BPA inhibited the synthesis and secretion of mucin 2., Significance: Our data suggest that BPA affected the secretory function of intestinal goblet cells by inducing mitochondrial dysfunction, oxidative stress, and apoptosis., (Copyright © 2019. Published by Elsevier Masson SAS.)

Lanthanum exerts adverse effects on the central nervous system. However, the mechanism underlying these adverse effects has not been clarified. It is known that oxidative stress plays an important role in neurological injuries induced by harmful factors. Nuclear factor erythroid 2-related factor (Nrf2) is very important in the response to oxidative stress in tissues and cells. The purpose of this study was to explore the effect of lanthanum chloride (LaCl3) on the spatial learning and memory of rats and to determine whether the Nrf2/antioxidant response element pathway acts in the hippocampus. Four groups of Wistar rats were exposed to 0 mM, 9 mM, 18 mM or 36 mM LaCl3 through their drinking water from the day of birth to 2 months after weaning. The results showed that LaCl3 impaired the spatial learning and memory of the rats, damaged the neuronal ultrastructure, increased reactive oxygen species levels and significantly down-regulated Nrf2 as well as the mRNA and protein expression of Nrf2-regulated genes, including NADP(H): dehydrogenase quinone 1, haeme oxygenase-1, superoxide dismutase 2, glutathione peroxidase 1, glutathione- S-transferase, γ-glutamine cysteine synthase and glutathione reductase, in the hippocampus. This study suggests that LaCl3 can impair the spatial learning and memory of rats, possibly by perturbing the Nrf2/antioxidant response element signalling pathway. [ABSTRACT FROM AUTHOR]

• BPA exposure induces oxidative stress in the kidney. • BPA exposure induces local inflammation in the kidney. • BPA exposure induces mitochondrial dysfunction in the kidney. • BPA exposure induces apoptosis in the kidney. • ATX against BPA-induced nephrotoxicity by maintaining mitochondrial function. Bisphenol A (BPA), a global environmental pollutant, has been reported to have the potential to induced organs toxicity. This study explored the potential benefits of astaxanthin (ATX), a natural antioxidant, against BPA toxicity in the kidney, and explored whether mitochondria are involved in this condition. Male Wistar rats were fed with a vehicle, BPA, BPA plus ATX, ATX and were evaluated after five weeks. ATX treatment significantly reversed BPA-induced changes in body weight, kidney/body weight, and renal function related markers. When treated simultaneously with ATX, the imbalance of the oxidative-antioxidant status caused by BPA was also alleviated. The high expression of BPA-induced pro-inflammatory cytokines were inhibited by ATX treatment. ATX treatment also lessened the effects of BPA-induced caspase-3, -8, -9 and -10 gene expression and enzyme activity. The benefits of ATX were associated with enhanced mitochondrial function, which led to increased mitochondrial-encoded gene expression, mitochondrial copy number, and increased mitochondrial respiratory chain complex enzyme activity. Our results demonstrate the efficacy of ATX in protecting BPA-induced kidney damage, in part by regulating oxidative imbalance and improving mitochondrial function. Collectively, these findings provide a new perspective for the rational use of ATX in the treatment of BPA-induced kidney disease. [ABSTRACT FROM AUTHOR]

Lanthanum (La) can damage the blood brain barrier when it enters the brain tissue, causing learning and memory dysfunction. Currently, few studies have focused on La-induced oxidative stress in choroid plexus epithelial cells, which can severely impair the normal function of the blood-cerebrospinal fluid barrier (BCSFB) and ultimately cause central nervous system dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element(ARE) signaling pathway is one of the major antioxidant systems and is vital in protecting cells against oxidative injury in rodents. In this study, Z310 cells were employed to construct BCSFB in vitro and treated with lanthanum chloride (LaCl 3); meanwhile, 40 μmol/L tert-butylhydroquinone and the corresponding concentration of LaCl 3 was used as the intervention groups. The results showed that LaCl 3 treatment markedly decreased Z310 cell viability, increased the necrosis rate, and then reduced the transepithelial electrical resistance value of BCSFB in vitro ; reactive oxygen species levels gradually increased, catalase and glutathione peroxidase activities decreased; furthermore, Nrf2 was significantly downregulated, and the expression of Nrf2 downstream genes such as heme oxygenase1, NADP(H): dehydrogenase quinone1, glutathione thiotransferase etc. noticeably decreased; in addition, interleukin-1β and tumour necrosis factor-α associated with Nrf2 activation noticeably increased. However, tert-butylhydroquinone could activate the Nrf2/AER signaling pathway and attenuate the Z310 cell oxidative damage induced by LaCl 3. Thus, the Nrf2/ARE signaling pathway is probably involved in weakening the BCSFB in vitro that is created by La-induced oxidative stress. Tert-butylhydroquinone can activate this pathway to reverse severe oxidative damage, which significantly strengthen the function of BCSFB. The nuclear factor erythroid 2-related factor/antioxidant response element pathway is probably involved in weakening the blood-cerebrospinal fluid barrier underlying resistance oxidative stress created by lanthanum. Tert-butylhydroquinone can reverse the oxidative damage in choroid plexus epithelial cells though activation of this pathway, which significantly strengthen the function of blood-cerebrospinal fluid. [Display omitted] • Lanthanum (La) can increase the permeability of the blood-cerebral spinal fluid barrier. • La led to oxidative stress resulting in the weaker antioxidant capacity of Z310 cell. • Tert-butylhydroquinone reduced the injured blood-cerebral spinal fluid barrier led by La. [ABSTRACT FROM AUTHOR]