ABSTRACT
BACKGROUND: Bisphenol-A (BPA) is an industrial chemical, used to manufacture polycarbonate and numerous plastic articles. It has been found to cause biological effects, mimic that of oestrogen. It belongs to a group of chemicals termed "endocrine disruptors" able to disrupt the chemical messenger system in the body. Aim of the study was to demonstrate the biological effects of BPA on the vagina of female rats, with the prediction of the neoplastic changes in relation to its potential impact. MATERIALS AND METHODS: Sprague-Dawley gravid dams were divided into three groups (10 per group): G1 - control group had an equivalent volume of sesame oil to that taken in the treated groups, G2 - group was administered by gavage 0.1 mg BPA/kg body weight (low-dose group) per day, and G3 - group was administered 50 mg BPA/kg body weight (high-dose group) per day, dissolved in sesame oil. Treatment was carried out on gestation days 10 through 20. The female offsprings of each group were weaned at day 21 and the vagina was dissected when became 3 months old for histological, immunohistochemical analysis (for detection of oestrogen receptors a [ERa], and the proliferation marker Ki-67), and ultrastructural study. RESULTS: The low dose group showed degeneration of the epithelial lining with focal patches of decreased epithelial layers. The high dose group revealed cytoplasmic hydropic degeneration, and the pyknotic nuclei of epithelial cells. Oestrogen receptors demonstrated a significant decrease of positive cells in low dose treated group and this decrease markedly accentuated in the high dose one. Positive nuclei for Ki-67 were markedly increased with increasing doses of BPA. Electron microscopic study revealed cytoplasmic degeneration, vacuolation and mitochondrial degeneration in both treated groups. CONCLUSIONS: BPA showed an obvious mix of degenerative and proliferative histological changes and clear damage of the cellular organelles. This stressful condition may predispose to neoplastic changes of the vagina.
ABSTRACT
BACKGROUND: Infection with the hepatitis C virus (HCV) causes acute hepatitis. This disease has a high probability of becoming chronic and leading to cirrhosis, but a more deadly consequence is hepatocellular carcinoma. Interferon alpha (IFN alpha)-based treatment combined with ribavirin is the major therapeutic choice available for the treatment of chronic HCV infection. AIMS: The scavenger receptor class B type I (SR-BI) or its human homologue CD36 and LIMPII Analogous-1 (hSR-BI/CLA-1) has recently been shown to interact with HCV envelope glycoprotein E2, thus suggesting that it might participate in entry of the virus into host cells. This rationale underlies current interest in the potential role of IFN alpha in hSR-BI/CLA-1 expression in HepG2 cells. RESULTS: It was shown that endogenous hepatocyte expression of hSR-BI/CLA-1 was suppressed by exposure to IFN alpha. Decreased hSR-BI/CLA-1 expression in IFN alpha-treated cells was due to lower transcriptional activity of the promoter. A potential pathway for the effect of IFN alpha on hSR-BI/CLA-1 promoter activity was identified when the inhibitory action of IFN was abrogated in signal transducer and activator of transcription 1 (STAT1)/STAT2 knocked-down cells. Exposure of HepG2 cells to IFN alpha elicited a rapid phosphorylation of STAT1/STAT2, a known target of IFN alpha signalling. In addition, the mutagenesis of a STAT1/STAT2 response element in the hSR-BI/CLA-1 promoter abolished the ability of IFN alpha to suppress promoter activity. CONCLUSIONS: Together, these results indicate that the STAT1/STAT2 pathway participates in IFN alpha inhibition of hSR-BI/CLA-1 expression, and raise the possibility that lowering the expression of this gene may be of therapeutic value for treating HCV infections.
