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1.
Bull Environ Contam Toxicol ; 102(1): 32-38, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30406814

RESUMO

Cadmium (Cd), an extremely toxic heavy metal is extensively used in modern era because of its constructive chemical and physical properties. Recently Cd contamination was estimated in India's major cities fresh water ecosystem, which may have firm impact on human health. Hence, this study was aimed to detect the time dependent effect of cadmium in fresh water fish C. gariepinus, a bioindicator species of water pollution. In a controlled environment, fishes were exposed to cadmium for different duration and analyzed for Cd accumulation. Cd induced toxicity was assessed by estimating metallothionein biomarker protein of heavy metal toxicity and histomorphometric changes in liver and kidney. Our results revealed that fish exposed to Cd induced apoptosis in fish tissues via induction of caspases and in contrast the metallothionein was also increased consistently with different doses of Cd exposure. Hence we conclude Cd induced structural damages to fishes are attributed to induction of caspases and estimating MT level in tissues can be effective biomarker to analyze the effect of acute environmental exposure to Cd.


Assuntos
Cádmio/toxicidade , Peixes-Gato , Metalotioneína/análise , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Água Doce/química , Índia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Espécies Sentinelas , Fatores de Tempo
2.
J Endocrinol Invest ; 40(1): 91-100, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27614457

RESUMO

PURPOSE: Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants acting as endocrine disruptors. Many researches evidenced that PCBs affect the male reproductive system in adult rats and it can transfer from mother to offspring through milk. We investigated whether the lactational exposure to PCBs affects the Sertoli cell function in F1 offspring. METHODS: Dams were orally treated with different doses of PCB-Aroclor 1254 (1, 2 and 5 mg/kg bw/day, respectively) from postpartum day 1-20. Male offspring rats were killed on PND 21 and PND 60. Testes were used both for histological study and to isolate Sertoli cell. Serum and testicular interstitial fluid (TIF) levels of testosterone, ABP and estradiol were analyzed by ELISA method. The mRNA and protein expressions of follicle-stimulating hormone (FSHR), androgen-binding protein (ABP), Inhibinß, androgen receptor (AR) and estrogen receptor (ERß) were studied using real-time PCR and immunoblotting, respectively. RESULTS: The testicular architecture was altered in PCB-treated groups of both prepuberal and puberal rats. Testosterone, estradiol and androgen-binding protein levels were altered in both serum and TIF in PCB treated groups. The gene expression level of FSHR, ABP, ERß and AR was decreased in a dose-dependent manner, whereas Inhibinß gene expression level was increased in PCB-treated groups. CONCLUSION: Lactational exposure to PCB affects both the histoarchitecture of testis, Sertoli cell maker and functional regulators in both prepuberal and puberal F1 male progeny.


Assuntos
Poluentes Ambientais/farmacologia , Lactação/efeitos dos fármacos , Bifenilos Policlorados/farmacologia , Puberdade/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Immunoblotting , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células de Sertoli/metabolismo , Testículo/efeitos dos fármacos , Testosterona/sangue
3.
Neurochem Res ; 42(2): 428-438, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27804010

RESUMO

There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.


Assuntos
Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Locomoção/fisiologia , Melatonina/farmacologia , Fármacos Neuroprotetores/farmacologia , Bifenilos Policlorados/toxicidade , Animais , Proteína 5 Relacionada à Autofagia/metabolismo , Córtex Cerebral/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar
4.
Neurochem Res ; 40(9): 1858-69, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26224288

RESUMO

Various epidemiological survey suggests that the central nervous system is the target for many environmental contaminants. One among them is Aroclor 1254, a mixture of polychlorinated biphenyls (PCBs) which explore a spectrum of biochemical and neurotoxic responses in humans and laboratory animals. Learning and motor coordination deficits are the profound effects of PCBs which may be related to cerebral dysfunction. The aim of the study is to elicit the protective effect of melatonin (Mel), a potent, blood brain permeable antioxidant against the effect of Aroclor 1254 on the signaling of glutamate-principal excitatory neurotransmitter and brain derived neurotrophic factor (BDNF) in the cerebral cortex of adult rats which plays a key role in brain functions. Adult male Wistar rats were grouped into four and treated intraperitonealy (i.p) Group I with corn oil (Control), Group II with PCBs (2 mg/kg/bwt), Group III with PCBs + Mel (2 mg/kg/bwt + 5 mg/kg/bwt) and Group IV with Mel (5 mg/kg/bwt). The protein expression of glutamate signaling molecules and mRNA expressions of GLAST, BDNF signaling molecules were analyzed. The results suggest that simultaneous melatonin treatment significantly attenuated the NMDA receptor mediated glutamate excitotoxicity and protects the inhibition of BDNF signaling caused by PCBs exposure in cerebral cortex of adult male rats. Schematic pathway illustrating the proposed mechanism by which melatonin protects against A1254 mediated glutamate induced neurodegeneration in the cerebral cortex of adult male rats. PCBs induced neurodegeneration is caused by the overactivation of NMDAR, followed by the activation of voltage dependent calcium channels leading to the increase in intracellular Ca(2+) that stimulates calpain. Calpain inturn inhibits the PKA α and neurtrophin BDNF, its receptor and downstream signaling MAPK pathway leading to neurodegeneration. Melatonin had scavenged the ROS produced by PCBS and decreased the NMDAR expression which inturn protected the cells from neurodegeneration.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Melatonina/farmacologia , Bifenilos Policlorados/toxicidade , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Canais de Cálcio Tipo N/metabolismo , Calpaína/metabolismo , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Masculino , RNA Mensageiro/genética , Ratos , Receptores de Glutamato/metabolismo , Transdução de Sinais
5.
Neurol Sci ; 35(2): 163-70, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23771516

RESUMO

Neuroblastoma is a neuroendocrine tumour derived from neural crest cells and it remains a major therapeutic challenge in pediatric oncology. As response rates to chemotherapy are low, surgery remains the only effective treatment but since many tumors have metastasized at the time of diagnosis, curative surgery is rarely achieved. Consequently, a substantial need for new therapeutic options emerges. Quercetin a flavonoid, has been reported to lower the risk of several cancers. This study was designed to investigate its effects on apoptosis induction in the N2a, a mouse neuroblastoma cell line. The cell viability was determined by dimethyl thiazolyl tetrazolium bromide assay and diamidino-2-phenylindole staining was performed to confirm the apoptosis. The gene expression of bcl-w, p53, p27 and protein expression of caspases (3 and 9), bax, cytochrome-c were studied. This in vitro outcome suggests that quercetin can be used as a potent anti-cancer drug in future.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Quercetina/farmacologia , Animais , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose , Western Blotting , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citocromos c/metabolismo , Expressão Gênica/efeitos dos fármacos , Indóis , Camundongos , Neuroblastoma/fisiopatologia , Reação em Cadeia da Polimerase , Proteínas/metabolismo , RNA Mensageiro/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
6.
Toxicol Lett ; 222(1): 45-54, 2013 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-23831945

RESUMO

Polychlorinated biphenyls (PCBs) are extremely toxic environmental contaminant speculated to accelerate neurochemical and behavioral damages. Developmental and behavioral development relies on the proper functioning of the endogenous neurotransmitters that remain the pivotal target of neurotoxicants. This study intent to evidence the neuroprotective efficacy of quercetin against PCBs induced hippocampal degeneration. Animals were sorted into four (n=6), Group I: received corn oil (vehicle) intraperitoneally (i.p.); Group II: received quercetin 50 mg/kg bwt (gavage); Group III: were induced with Aroclor 1254 (commercial mixture of PCB) at 2 mg/kg bwt (i.p); Group IV: received quercetin 50 mg/kg bwt (gavage) and along with PCBs 2 mg/kg bwt (i.p.) for 30 days. Cognitive behaviors such as learning and memory were assessed by 8-arm radial maze behavior test throughout the experimental period. Subsequently, anxiety and stress were studied by open field test at the termination of experiment. Hippocampal tissue and blood were collected after the intended experimental period to analyze the levels of oxidative stressors, antioxidants in tissue and estimation of neurotransmitters. Perhaps, PCBs evoke detrimental deterioration of the neurotransmitters and integrative antioxidant defense by elevation of reactive oxygen species (ROS). Concurrent treatment with quercetin prominently suppresses the oxidative stressors, improved the levels of enzymatic antioxidants and neurotransmitter levels significantly at the level of p<0.05. Behavioral analysis claims drastic revitalization of cognitive functions like learning and memory on treatment with quercetin. The results coalesced depicts neurotoxicity stimulated by PCBs is augmented by simultaneous quercetin administration.


Assuntos
Ansiolíticos , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Hipocampo/patologia , Doenças Neurodegenerativas/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Quercetina/farmacologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/prevenção & controle , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Doenças Neurodegenerativas/patologia , Neurotransmissores/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Estresse Psicológico/psicologia , Substâncias Reativas com Ácido Tiobarbitúrico
7.
Environ Toxicol Pharmacol ; 36(1): 152-63, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23619521

RESUMO

Polychlorinated biphenyls (PCBs) are widespread persistent environmental contaminants that display a complex spectrum of toxicological properties, including neurotoxicity. Studies have shown that PCBs increase oxidative stress in brain, leading to apoptosis. The progressive loss of neurons in cerebral cortex and cerebellum, leads to various neurodegenerative diseases. Hence the present study is designed to determine PCBs toxicity toward neuronal cells and whether it could be inhibited by potent antioxidant melatonin. Four groups of adult male Wistar rats were treated for 30 days with corn oil, PCBs, PCBs+Mel and Melatonin, respectively. After treatment period the rats were euthanized and the brain was dissected to isolate cerebral cortex and cerebellum. The neuronal cells alone were then separated from the isolated brain regions, to detect the mRNA levels of apoptotic and neurofilament gene, a neuronal specific marker. Our results suggests that PCBs induces apoptosis in neuronal cells which is subsided by the anti apoptotic effect of melatonin.


Assuntos
Poluentes Ambientais/toxicidade , Melatonina/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Bifenilos Policlorados/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 8/genética , Caspase 8/metabolismo , Células Cultivadas , Cerebelo/citologia , Córtex Cerebral/citologia , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , NF-kappa B/genética , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Wistar
8.
Hum Exp Toxicol ; 32(7): 706-20, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23155198

RESUMO

Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances associated with carcinogenic and tumor-promoting effects as well as neurotoxic properties. Reactive oxygen species, which is produced from PCBs, alters blood-brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements and redistribution and disappearance of tight junction proteins (TJPs) like claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and other vegetables, appears to protect brain cells against oxidative stress, a tissue-damaging process associated with Alzheimer's and other neurodegenerative disorders. The aim of this study is to analyze the role of quercetin on oxidative stress markers and transcription of transmembrane and cytoplasmic accessory TJPs on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were divided into the following four groups. Group I: received only vehicle (corn oil) intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received quercetin alone gavage. From the experiment, the levels of hydrogen peroxide, lipid peroxidation and thiobarbituric acid reactive substances were observed to increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and 20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP in rats exposed to PCBs is decreased and is retrieved to the normal level simultaneously in quercetin-treated rats. Hence, quercetin can be used as a preventive medicine to PCBs exposure and prevents neurodegenerative disorders.


Assuntos
Encéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Fármacos Neuroprotetores/farmacologia , Bifenilos Policlorados/toxicidade , Quercetina/farmacologia , Animais , Encéfalo/metabolismo , Feminino , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Proteínas de Junções Íntimas/genética
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