Volume 1 Issue 1
Research Article: Exposure to BDE-47 Alters Thyroid Hormone Levels and Gene Transcription in the Hypothalamic-Pituitary-Thyroid Axis of Zebra?sh Larvae (Danio Rerio)
Xin Ren, Hang Zhao, and Xuesong Zhao*
2,2',4,4'-Tetrabromodi-phenyl ether (BDE-47) has the potential to disrupt thyroid hormone homeostasis, but the molecular mechanisms underlying this process have not yet been clari?ed. In the present study, zebra?sh embryos were BDE-47 (0, 1, 5, or 10 μg/L) from fertilization to 14 d thereafter (dpf). The whole-body content of Thyroid Hormones (THs) and the transcription of genes and proteins related to the Hypothalamic-Pituitary-Thyroid (HPT) axis were analyzed. Abnormal morphologies and inhibition of body-weight gain have been associated with decreased levels of Thyroid Hormones (THs) in zebrafish larvae. BDE-47 exposure (up to 10 μg/L) significantly reduced Thyroxine (T4), indicating thyroid-related endocrine disruption. The gene expression levels of CRH and TSHβ were significantly induced by BDE-47 exposure (5 and 10 μg/L). The transcription of genes involved in the synthesis of TH proteins, NIS, TG, Pax8 and Nkx2.1 were signi?cantly up-regulated by BDE-47 exposure (5 and 10 μg/L). Furthermore, the protein level of TG was signi?cantly up-regulated in a concentration-dependent manner. The expression of Deio2 was also signi?cantly up-regulated in BDE-47-treated groups (5 and 10 μg/L), possibly as a compensatory response to the decreased T4 levels. The transcription of TRa and TRβ was down-regulated in a concentration-dependent manner. However, BDE-47 exposure downregulated both the transcriptional and protein levels of TTR. The exposure to BDE-47 (10 μg/L) signi?cantly increased the transcription of the UGT1 gene. The results described above that BDE-47 can alter gene and protein expression in the HPT axis, which may subsequently contribute to BDE-47-induced thyroid disruption.
Cite this Article: Ren X, Zhao H, Zhao X. Exposure to BDE-47 Alters Thyroid Hormone Levels and Gene Transcription in the Hypothalamic-Pituitary-Thyroid Axis of Zebra?sh Larvae (Danio Rerio). Int J Toxicol Curr Res. 2017;1(1): 023-032.
Published: 26 September 2017
Research Article: Crocin Affects Passive Avoidance Memory Following Formaldehyde-Induced Neurotoxicity in a Rat Model
Mahsa Mashak shahabadi, Seyyedeh Zahra Mousavi, Seyyedeh Elaheh Mousavi and Majid Hassanpour Ezzati*
Crocin, the main constituent of Crocus sativus L., protected against inflammation-induced neurotoxicity and improved learning behavior. Also, crocin inhibited production of inducible nitric oxide synthase. Studies also indicated an interaction between NO and Formaldehyde (FA) -induced neurotoxicity. In this study, effect of crocin on memory and body weight changes in neurotoxicity induced by FA was evaluated in a rat model. Moreover, the possible involvement of NO on protective effects of crocin was investigated. FA (5 mg/kg) was administered intraperitoneally for 5 consecutive days. Effect of crocin post-treatment (25, 50 and 100 mg/kg, i.p.) on FA neurotoxicity was evaluated on passive avoidance memory. To determine the contribution of NO, a NO synthesis precursor, L-arginine (L-Arg) 100 mg/kg, i.p.; and a nonselective NO synthase inhibitor N (G)-Nitro-L-Arginine Methyl Ester, (L-NAME) (10 mg/kg, i.p.) were used. Then, the hippocampus was evaluated histologically. FA caused weight loss and increased mortality rate. It also impaired fear memory. On the contrary, crocin (25 mg/kg, i.p.) reduced mortality rate, weight loss and hippocampal tissue damage induced by FA. Further, it improved the memory impairment by reducing the latency time and the hippocampus cell loss. Moreover, L-NAME reversed the protective effects of crocin, nevertheless; L-Arg enhanced the effects of crocin. Pretreatment with crocin protected the central and peripheral damages. Exogenous NO ameliorated the neuroprotective effect of crocin; as a result, crocin exerted its protective effects through NO up-regulation. Results of the present study suggest that inhibition of NO synthesis may exaggerate the neurotoxic effects of FA.
Cite this Article: Shahabadi MM, Mousavi SZ, Mousavi SE, Ezzati HM. Crocin Affects Passive Avoidance Memory Following Formaldehyde-Induced Neurotoxicity in a Rat Model. Int J Toxicol Curr Res. 2017;1(1): 015-022.
Published: 21 September 2017
Research Article: Aluminum Oxide Nanoparticles Induced Cognitive Deficits and Oxidative Stress in Frontal Cortex and Cerebellum of Rat
Imen Mrad, Mohsen Sakly and Salem Amara*
Aluminum oxide nanoparticles (Al2O3-NPs) are widely used in industry. Nevertheless the information about its toxicity on humans and environment is still deficient. The present study aimed to investigate the effect of four intravenous injections of Al2O3-NPs (20mg /kg body weight) on Wistar male rat brain. For this purpose we highlight behavioral consequences as well as oxidative response, Acetylcholinesterase (AChE) activity, Aluminum (Al) biodistribution, and histological changes in Frontal Cortex (FC) and Cerebellum (Cb). In anxiety related behaviors, Al2O3-NPs treated rats entered less frequently and spent more time in the plus maze's enclosed arms than control rats. Al2O3-NPs exposure increased the Malondialdehyde (MDA) and thiol group levels in FC and decreased Catalase Activity (CAT) in this latter. Furthermore, Superoxide Dismutase (SOD) and AChE activities decreased both in FC and Cb. Glutathione Peroxidase Activity (GPx) decreased only in Cb. Sub-acute Al2O3-NPs exposure increased contents of Al and Magnesium (Mg) in FC and Cb. Nevertheless, calcium (Ca) contents decreased in the both same structures while iron (Fe) contents decreased only in FC compared to the control. The most pronounced histological changes were observed in FC tissue included astroglyosis, vascular congestion, neuronal degeneration, presence of edema and necrosis, degenerative neurofibrillary tangles and vacuolated cytoplasm.
Cite this Article: Mrad I, Sakly M, Amara S. Aluminum Oxide Nanoparticles Induced Cognitive Deficits and Oxidative Stress in Frontal Cortex and Cerebellum of Rat. Int J Toxicol Curr Res. 2017;1(1): 007-014.
Published: 15 September 2017
Research Article: Effect Of Methyl- Propyl (MP), Methyl-Butyl (MB), and Methyl-Propyl-Butyl (MPB) Mixtures on the Proliferation, DNA Fragmentation and Estradiol Secretion of MCF-7 Breast Cancer Cells and MCF-10A Normal Breast Epithelial Cells
Ewa Lucja Gregoraszczuk*
Since parabens are used as preservatives in cosmetics as mixtures, here we aimed to compare the effects of Methyl- Propyl (MP), Methyl-Butyl (MB), and Methyl-Propyl-Butyl (MPB) on MCF-7 (breast cancer cells) and MF-10A (non-cancer breast epithelial cells) proliferation (Alamar Blue assay), DNA fragmentation ( ELISA), and estradiol (E2) secretion (ELISA). Cells were exposed to mixtures at a concentration of 20 N, either alone or supplemented with parabens together with 10 nM 17β-estradiol. ICI 182,780 (100 nM) was used to demonstrate the involvement of Estradiol Receptor (ER) in the action of the paraben mixture. For the MCF-7 cells, all mixtures increased cell proliferation and inhibited DNA fragmentation. No synergistic action with E2 was observed, and only the MPB increased E2 secretion by MCF-7 cells. For the MCF-10A cells, none of the mixtures affected cell proliferation, and only MPB decreased DNA fragmentation. No mixture affected the secretion of estradiol in either cell line. The ICI 182,780 inhibitory effect on parabens stimulated cell proliferation only in ER+ cells, thereby confirming their ER-mediated action. In conclusion, based on the presented results we suggest that simultaneous application of more than one paraben might promote the progression of malignancy but not initiation of cancer.
Cite this Article: Gregoraszczuk EL. Effect Of Methyl- Propyl (MP), Methyl-Butyl (MB), and Methyl-Propyl-Butyl (MPB) Mixtures on the Proliferation, DNA Fragmentation and Estradiol Secretion of MCF-7 Breast Cancer Cells and MCF-10A Normal Breast Epithelial Cells. Int J Toxicol Curr Res. 2017;1(1): 001-006.
Published: 08 September 2017
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