Neurochemical impact of bisphenol A in the hippocampus and cortex of adult male albino rats.

Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of polycarbonated plastics and epoxy resins and line metal beverage cans. Growing evidence suggests that BPA acts directly on neuronal functions as it is lipophilic and could accumulate in the brain. The present study aims to investigate the effect of two doses of BPA (10 mg/kg for 6 and 10 weeks and 25 mg/kg for 6 weeks) on excitatory (glutamate and aspartate) and inhibitory (γ-aminobutyric acid, glycine, and taurine) amino acid neurotransmitter levels in the cortex and hippocampus. This study extends to investigate the effect of BPA on acetylcholinesterase (AchE) activity and some oxidative stress parameters in the two regions. In the cortex, a significant increase in the excitatory and a significant decrease in the inhibitory amino acids occurred after BPA (10 mg/kg for 10 weeks and 25 mg/kg for 6 weeks). This was accompanied by a significant increase in lipid peroxidation, nitric oxide, and reduced glutathione after 6 weeks of BPA (25 mg/kg). In the hippocampus, a significant increase in the excitatory and inhibitory amino acid neurotransmitters occurred after 6 weeks of BPA. Hippocampal lipid peroxidation increased significantly after BPA exposure and hippocampal reduced glutathione increased significantly after 6 weeks of BPA exposure (10 mg/kg). BPA induced a significant increase in cortical and hippocampal AchE activity. The present neurochemical changes in the cortex and hippocampus suggest that BPA induced a state of excitotoxicity and oxidative stress. This may raise concerns about the exposure of humans to BPA due to its wide applications in industry.

Khadrawy YA ，Noor NA ，Mourad IM ，Ezz HS ... -  《-》

Influence of α-tocopherol and α-lipoic acid on bisphenol-A-induced oxidative damage in liver and ovarian tissue of rats.

Bisphenol A (BPA) is a commonly used material in daily life, and it is argued to cause oxidative stress in liver and ovarian tissue. α-Lipoic acid (ALA) and α-tocopherol (ATF), two of the most effective antioxidants, may play a role in preventing the toxic effect. Therefore, the purpose of this study was to examine the beneficial effects of ALA, ATF, and that of ALA + ATF combination on oxidative damage induced by BPA. Female Wistar rats were divided into five groups (control, BPA, BPA + ALA, BPA + ATF, and BPA + ALA + ATF). BPA (25 mg/kg/day), ALA (100 mg/kg/day), and ATF (20 mg/kg/day) were administered for 30 days.  The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver malondialdehyde (L-MDA) and glutathione peroxidase (L-GPx), and ovarian malondialdehyde (Ov-MDA) and nitric oxide (Ov-NO) were significantly higher in the BPA-treated groups compared with the control group. The levels of AST and ALT decreased in the BPA + ALA, BPA + ATF, and BPA + ALA + ATF groups compared with the BPA group. Similarly, BPA + ALA or BPA + ATF led to decreases in L-MDA and Ov-MDA levels compared with the BPA group. However, the BPA + ALA + ATF group showed a significant decrease in L-MDA levels compared with the BPA + ALA group and the BPA + ATF group. The levels of L-GPx decreased in the BPA + ATF and the BPA + ALA + ATF groups compared with the BPA group. The administration of ATF and ALA + ATF significantly decreased the Ov-NO levels.  This study demonstrates that BPA causes oxidative damage in liver and ovarian tissues. ALA, ATF, or their combination were found to be beneficial in preventing BPA-induced oxidative stress.

Avci B ，Bahadir A ，Tuncel OK ，Bilgici B ... -  《-》

Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A: Mechanism of hepatotoxicity and biomarker discovery.

Bisphenol A (BPA), discovered to be an artificial estrogen, has been shown to leach from some containers and mediate oxidative damage to cells and tissues and to be involved in reproductive disorders, obesity, diabetes, and liver dysfunction. In the current study, we investigated the effects of oral chronic exposure to low dose of BPA (0.5 mg kg-1) on the protein and phosphoprotein expression profiles in male Wistar rat liver using a gel-based proteomics approach based on two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry identification. Our results showed that BPA exposure affected the levels of proteins and phosphoproteins involved in diverse biological processes associated with hepatotoxicity, fatty liver, and carcinoma. Moreover, we analyzed the effects of BPA on oxidative stress by assessing levels of malondialdehyde (MDA), a marker of lipid peroxidation, and reduced glutathione (GSH), a non-enzymatic antioxidant agent, in the liver. As expected BPA induced oxidative stress indicated by increased levels of MDA and decreased GSH content in the liver. In conclusion, chronic oral exposure of rats to BPA leads to increased oxidative stress in the liver and major alterations in the liver proteome and phosphoproteome, which may contribute to the pathophysiology of liver diseases.

Vahdati Hassani F ，Abnous K ，Mehri S ，Jafarian A ，Birner-Gruenberger R ，Yazdian Robati R ，Hosseinzadeh H ... -  《-》

Impact of low-dose chronic exposure to bisphenol A and its analogue bisphenol B, bisphenol F and bisphenol S on hypothalamo-pituitary-testicular activities in adult rats: A focus on the possible hormonal mode of action.

Bisphenol A an estrogen-mimic endocrine disrupting chemical, used to manufacture polycarbonate plastics and epoxy resins with toxic effects for male reproduction. Due to its toxicity, industries have started to replace it with other bisphenols. In this study, the toxicity of BPA analogues (BPB, BPF and BPS) was evaluated in a chronic study. We investigated whether the chronic exposure to low bisphenols doses affects spermatogenesis with outcomes on oxidative stress and male reproductive system. Male rats (22 day old) were exposed to water containing 0.1% ethanol for control or different concentrations of BPA and its analogues BPB, BPF and BPS (5, 25 and 50 μg/L) in drinking water for 48 weeks. Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organs weights. Oxidative stress in the testis was significantly elevated while sperm motility, Daily sperm production (DSP) and number of sperm in epididymis were reduced. Plasma testosterone, LH and FSH concentrations were reduced and estradiol levels were high in 50 μg/L exposed group. These results suggest that exposure to BPA and its analogues for chronic duration can induce structural changes in testicular tissue and endocrine alterations in the male reproductive system.

Ullah A ，Pirzada M ，Jahan S ，Ullah H ，Turi N ，Ullah W ，Siddiqui MF ，Zakria M ，Lodhi KZ ，Khan MM ... -  《-》

Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats.

Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing of polycarbonate plastics and epoxy resins. BPA and other endocrine disrupting chemicals (EDCs) act via multiple mechanisms including interference with mitochondrial functions. Mitochondria are the hub of cellular energy pool and hence are the target of many EDCs. We studied perturbation of activities of mitochondrial enzymes by BPA and its possible role in hepatotoxicity in Wistar rats. Rats were exposed to BPA (150 mg/kg, 250 mg/kg, 500 mg/kg per os, for 14 days) and activities of enzymes of mitochondrial electron transport chain (ETC) were measured. Besides, other biochemical parameters such as superoxide generation, protein oxidation, and lipid peroxidation (LPO) were also measured. Our results indicated a significant decrease in the activities of enzymes of mitochondrial ETC complexes, i.e., complex I, II, III, IV, and V along with significant increase in LPO and protein oxidation. Additionally, a significant increase in mitochondrial superoxide generation was also observed. All these findings could be attributed to enhanced oxidative stress, decrease in reduced glutathione level, and decrease in the activity of superoxide dismutase in rat liver mitochondria isolated from BPA-treated rats. BPA treatment also caused a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase indicating its potential hepatotoxicity. Furthermore, histopathological findings revealed marked edema formation, hepatocellular degeneration, and necrosis of liver tissue in BPA-exposed rats. In conclusion, this study provides an evidence of impaired mitochondrial bioenergetics and liver toxicity after high-dose BPA exposure in rats. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1922-1934, 2016.

Khan S ，Beigh S ，Chaudhari BP ，Sharma S ，Aliul Hasan Abdi S ，Ahmad S ，Ahmad F ，Parvez S ，Raisuddin S ... -  《-》