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1.
Environ Health Prev Med ; 24(1): 41, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182008

RESUMO

OBJECTIVE: Bisphenol A (BPA) is a monomer primarily used in the production of polycarbonate plastic and epoxy resins. Bisphenol F (BPF) is apparently the main BPA replacement that is used increasingly. BPF has been detected in canned food, thermal paper receipts, and soft drinks. In the present experiment, we did both in vitro and in vivo studies to evaluate the effect of low and high-dose BPF exposures on testosterone concentration, oxidative stress, and antioxidants activity in reproductive tissues of male rats. METHODS: Adult (80-90 days old) male Sprague Dawley rats (n = 36) obtained from the rodent colony of Animal Sciences Department of Quaid-i-Azam University. The direct effects of BPF on the antioxidant enzymes and testosterone secretion were measured in vitro and in vivo studies. In an in vivo experiment, adult male Sprague Dawley rats (n = 42) were exposed to different concentrations of bisphenol F (1, 5, 25, and 50 mg/kg/d) for 28 days. Various biochemical parameters were analyzed including the level of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), reactive oxygen species (ROS), and lipid peroxidation (LPO). Moreover, sperm motility, daily sperm production (DSP), comet assay, and histological analysis were performed. RESULTS: In vitro study showed that BPF exposure significantly (p < 0.05) induced oxidative stress biomarkers, i.e., ROS and LPO, while it did not change antioxidant enzyme and testicular testosterone concentration. Whereas, an in vivo study revealed that BPF induced dose-dependent effect and high-dose (100 mg/kg) exposure of BPF significantly reduced tissue protein (p < 0.05) content, CAT (p < 0.001), SOD (p < 0.05), and POD (p < 0.05) levels while significantly (p < 0.05) augmented ROS and lipid peroxidation. Furthermore, BPF reduces testosterone, LH, and FSH secretion in a dose-dependent manner. Significant (p < 0.001) reduction in plasma and intra-testicular testosterone, LH, and FSH was noticed at 100 mg/kg BFP dose. High-dose exposure reduces spermatogenesis. CONCLUSION: BPF showed an antagonistic effect on male reproductive hormones and induce alterations in testicular morphology. Increased oxidative stress and decreased testicular antioxidant status might be the underlying mechanism of BFP-induced testicular toxicity.


Assuntos
Antioxidantes/metabolismo , Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Testosterona/metabolismo , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley
2.
Toxicol Ind Health ; 35(4): 294-303, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30871434

RESUMO

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report the mechanisms by which BPA and three of its analogues bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) cause generation of reactive oxygen species (ROS), sperm DNA damage, and oxidative stress in both in vivo and in vitro rat models. Sperm were incubated with different concentrations (1, 10, and 100 µg/L) of BPA and its analogues BPB, BPF, and BPS for 2 h. BPA and its analogues were observed to increase DNA fragmentation, formation of ROS, and affected levels of superoxide dismutase at higher concentration groups. In an in vivo experiment, rats were exposed to different concentrations (5, 25, and 50 mg/kg/day) of BPA, BPB, BPF, and BPS for 28 days. In the higher dose (50 mg/kg/day) treated groups of BPA and its analogues BPB, BPF, and BPS, DNA damage was observed while the motility of sperm was not affected.


Assuntos
Compostos Benzidrílicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Superóxido Dismutase/metabolismo
3.
Food Chem Toxicol ; 121: 24-36, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30120946

RESUMO

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.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Testículo/efeitos dos fármacos , Animais , Compostos Benzidrílicos/administração & dosagem , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/administração & dosagem , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Espermatogênese/efeitos dos fármacos , Sulfonas/administração & dosagem , Superóxido Dismutase/metabolismo , Testículo/enzimologia , Testículo/metabolismo , Testosterona/sangue
4.
Chemosphere ; 209: 508-516, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29940534

RESUMO

Bisphenol A (BPA) is used as the main component of many consumer products such as infant's feeding bottles, coatings of beverages, and food cans. BPA can migrate into the environment, and it has been detected in the saliva, blood, and food. BPA leakage from many consumer products resulted in a ban on its use in many countries where alternatives to BPA were introduced into the market. BPA alternatives such as bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) have a similar chemical structure and binding ability for estrogen receptor (ER), which shows toxicological effects in animals. In the present study, comparative effects of exposure to BPA and its analogs BPB, BPF, and BPS on testosterone concentration in the rat testis were evaluated by in vitro and in vivo approaches in which oxidative stress markers and antioxidant enzyme activities in reproductive tissues were determined. In the in vivo study, male rats were exposed to different concentrations of BPA and its analogs BPB, BPF, and BPS (5, 25, and 50 mg/kg/day) for 28 days. In the in vitro exposure study, antioxidant enzyme activities and oxidative stress markers were induced in the testes, whereas testosterone production was reduced. In the in vivo exposure study, we observed that antioxidant enzyme activities and protein content were reduced, whereas reactive oxygen species and lipid profile were increased in the treated groups compared to the control group. The present comparative study on BPA and its analogs, namely, BPB, BPF, and BPS suggests the toxic effect of these chemicals on the testes and spermatogenesis, and we also observed that these chemicals induce oxidative stress in the reproductive tissues of male rats.


Assuntos
Compostos Benzidrílicos/toxicidade , Sequestradores de Radicais Livres/toxicidade , Fenóis/toxicidade , Espermatozoides/patologia , Sulfonas/toxicidade , Testículo/patologia , Animais , Técnicas In Vitro , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
5.
J Ovarian Res ; 10(1): 62, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28915843

RESUMO

BACKGROUND: PCOs is a heterogeneous disorder with anovulation/oligo ovulation usually taken as oligo menorrhoea or amenorrhoea, hyperandrogenemia, hirsutism, acne, androgen alopecia and polycystic ovaries as the key diagnostic feathers. The study was undertaken to investigate the possible protective and ameliorating effects of GABA in Letrozole induced PCOS model in rats by targeting insulin resistance. METHODS: PCOs in Adult female rat was induced by the daily gastric administration of letrozole (1 mg/kg/day) in CMC (0.5%) for 36 days. Rats were given metformin (2 mg/kg), GABA (100 mg/kg/day) and GABA (500 mg/kg/day) along with letrozole. One group severed as vehicle control. On the 37 day, the animals were euthanized, and anthropometrical, biochemical (glucose, insulin, lipids, testosterone, Estradiol, Progesterone, oral glucose tolerance test, total protein content in ovary, cholesterol level, triglyceride, HDL, LDL), Antioxidants (CAT, POD, GSR, ROS, GSH, TBARS), and histopathological evaluation of ovaries were carried out. Daily colpocytological examination was also carried out until the termination. RESULTS: Both the doses of GABA significantly reduced body weight, body mass index and testosterone. While the levels of CAT, SOD, POD and Estradiol (E2) were significantly increased in the both doses of GABA. A favourable lipid profile, normal glucose tolerance, and decreased in the percentage of estrus smears were observed. Histopathological examination of ovary revealed a decreased in the number of cystic follicles, and decreased in the adipocytes respectively. The effects observed with GABA were comparable to that with metformin. CONCLUSION: The results suggest that GABA treatment has shown protective effect in PCOs and provide beneficial effect either by reducing insulin resistance or by inducing antioxidant defence mechanisms.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico , Antagonistas de Androgênios/farmacologia , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Estradiol/sangue , Feminino , Resistência à Insulina , Letrozol , Nitrilas , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Peroxidase/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Substâncias Protetoras/farmacologia , Ratos , Reprodução/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testosterona/sangue , Triazóis , Ácido gama-Aminobutírico/farmacologia
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