ABSTRACT
Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is known to cause testicular toxicity in animals. In the present study, the effects of ZEA on spermatogenesis and possible mechanisms involved in germ cell injury were examined in rats. Ten-week-old Sprague-Dawley rats were treated with 5 mg/kg i.p. of ZEA and euthanized 3, 6, 12, 24 or 48 h after treatment. Histopathologically, spermatogonia and spermatocytes were found to be affected selectively. They were TUNEL-positive and found to be primarily in spermatogenic stages I-VI tubules from 6 h after dosing, increasing gradually until 12 h and then gradually decreasing. Western blot analysis revealed an increase in Fas and Fas ligand (Fas-L) protein levels in the ZEA-treated rats. However, the estrogen receptor (ER)alpha expression was not changed during the study. Collectively, our data suggest that acute exposure of ZEA induces apoptosis in germ cells of male rats and that this toxicity of ZEA is partially mediated through modulation of Fas and Fas-L systems, though ERalpha may not play a significant role.
Subject(s)
Animals , Male , Rats , fas Receptor/immunology , Apoptosis/drug effects , Estrogens, Non-Steroidal/toxicity , Fas Ligand Protein/immunology , Histocytochemistry , Immunoblotting , In Situ Nick-End Labeling , Random Allocation , Rats, Sprague-Dawley , Spermatocytes/cytology , Spermatogenesis/drug effects , Spermatogonia/drug effects , Testis/cytology , Zearalenone/toxicityABSTRACT
Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -alpha and -beta, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 micrometer). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-alpha and ER-beta compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-beta estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-kappaB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-kappaB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-kappaB pathway may be more closely involved in BPA-induced neuronal toxicity.
Subject(s)
Animals , Rats , Apoptosis/drug effects , Blotting, Western , Cell Differentiation/drug effects , Cell Survival/drug effects , Estradiol/analogs & derivatives , Estrogens, Non-Steroidal/toxicity , Flavonoids/pharmacology , NF-kappa B/metabolism , Neurons/drug effects , PC12 Cells , Phenols/toxicity , Receptors, Estrogen/metabolism , Tamoxifen/pharmacologyABSTRACT
Several sex steroids and estrogenic drugs are genotoxic in varying conditions and cause oxidative stress, which has been a field of interest to study the molecular mechanism of the genetic damage. Among the estrogenic drugs, a strong toxic effect is exerted by diethylstilbestrol (DES). In the present study it has been attempted to study its genotoxic effects in human lymphocyte assay system along with ameliorative or anticlastogenic effects of vitamin C. The drug was used with different dosage of concentrations on human lymphocytes administered in vitro. The parameters used were Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs). Higher levels of clastogeny and SCEs have been observed indicating significant damaging effect by the drug. Interesting ameliorating effects were observed in the presence of vitamin C which is a well-known antioxidant. The results support the possibility of practical application of natural protectors against the mutagenic/oenotoxic action of chemical mutagens.
Subject(s)
Ascorbic Acid/pharmacology , Cells, Cultured , Chromosome Aberrations/drug effects , Chromosomes/drug effects , Diethylstilbestrol/toxicity , Estrogens, Non-Steroidal/toxicity , Humans , Lymphocytes/drug effects , Sister Chromatid Exchange/drug effectsABSTRACT
Os fitoestrogênios säo substâncias vegetais näo esteróides, com atividades estrogênicas agonistas e antagonistas. Possuem açäo estrogênica considerada fraca, se comparados aos estrogênios naturais e sintéticos e säo encontrados principalmente na soja e seus derivados. Muitos autores têm avaliado a possibilidade do uso dos fitoestrogênios como opçäo alternativa de terapia de reposiçäo hormonal (TRH), particularmente para os casos de pacientes com contra-indicaçöes para as terapias convencionais. No presente artigo säo revisados aspectos relevantes acerca das propriedades, metabolismo e aplicabilidade dos fitoestrogênios.