Soraya S Smaili

Universidade Federal de São Paulo, San Paulo, São Paulo, Brazil

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Publications (78)265.78 Total impact

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    ABSTRACT: Parkinson's disease is a neurodegenerative disorder characterized by motor impairment, cognitive decline and psychiatric symptoms. Schinus terebinthifolius Raddi, Anacardiaceae, had been studied for its anti-inflammatory and antioxidant properties, and in this study, the stem bark was evaluated for the neuroprotective effects on behavioral and biochemical alterations induced by administrations of rotenone in rats. Behavioral evaluations were performed using open-field and rotarod. The in vitro and in vivo antioxidant activities were determined by the DPPH radical scavenging activity and lipid peroxidation method respectively. The administration of rotenone (3mg/kg, s.c.) produced hypolocomotion, increase of immobility and muscle incoordination, while the treatment with S. terebinthifolius stem bark extract (150, 300 and 600mg/kg p.o.) for seven days prevented rotenone-induced dysfunctional behavior. Biochemical analysis of the substantia nigra, striatum and cortex revealed that rotenone administration significantly increased lipid peroxidation, which was inhibited by treatment with all doses of S. terebinthifolius. The results suggested neuroprotective effect of S. terebinthifolius possibly mediated through its antioxidant activity, indicating a potential therapeutic benefit of this species in the treatment of Parkinson's disease.
    Full-text · Article · Jan 2016 · Revista Brasileira de Farmacognosia
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    Daniel J Klionsky · Kotb Abdelmohsen · Akihisa Abe · Md Joynal Abedin · Hagai Abeliovich · Abraham Acevedo Arozena · Hiroaki Adachi · Christopher M Adams · Peter D Adams · Khosrow Adeli · [...] · Xiao-Feng Zhu · Yuhua Zhu · Shi-Mei Zhuang · Xiaohong Zhuang · Elio Ziparo · Christos E Zois · Teresa Zoladek · Wei-Xing Zong · Antonio Zorzano · Susu M Zughaier ·
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    ABSTRACT: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
    Full-text · Article · Jan 2016 · Autophagy
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    ABSTRACT: Recently, palladium complexes have been extensively studied as cyclization of these complexes by cyclometallation reactions increased their stability making them promising antitumor compounds. In this study, we have investigated apoptosis induced by the Biphosphinic Paladacycle Complex (BPC11) and possible cross talk between apoptosis and autophagy in cell line models of metastatic (Tm5) and non-metastatic (4C11-) melanoma. The BPC11-induced cell death in melanoma involved the lysosomal-mitochondrial axis, which is characterized by LMP, CatB activation and increased Bax protein levels following its translocation to mitochondria. Mitochondrial hyperpolarization, followed by membrane potential dissipation and cleavage of caspase-3, also resulted in cell death after 24 h of incubation. We also found that BPC11-mediated LC3II formation and increased p62 protein levels, suggesting blocked autophagy, probably due to LMP. Interestingly, the treatment of Tm5 and 4C11(-) cells with 3-methyladenine (3-MA), an inhibitor of the initial stage of autophagy, potentiated the effects of BPC11. We conclude that BPC11 is an anti-melanoma agent and that autophagy may be acting as a mechanism of melanoma cells resistance. Also, these data highlight the importance of studies involving autophagy and apoptosis during pre-clinical studies of new drugs with anticancer properties.
    No preview · Article · Nov 2015 · European Journal of Medicinal Chemistry
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    Soraya S. Smaili
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    ABSTRACT: Neste artigo foi abordado o enlace entre Oriente e Ocidente nas questões sociais e geopolíticas do século XX e início do XXI. Realiza-se uma breve análise sobre o colonialismo europeu e a sua construção considerando o mundo árabe e islâmico, os fluxos migratórios para os países centrais e a origem do fundamentalismo no Ocidente. As questões atuais se desdobram a partir da construção do orientalismo, da dominação política e econômica que levou à formação de estereótipos e preconceitos com o árabe e o islã. O objetivo é apresentar elementos para uma reflexão a respeito da migração dos árabes e muçulmanos no contexto das guerras e conflitos do século XX e início deste século. Também visa esclarecer a origem dos estereótipos e reforçar a necessidade do conhecimento do outro para que o diálogo e a coexistência estejam no centro do debate.
    Preview · Article · Aug 2015
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    ABSTRACT: Acute renal failure is a common complication caused by Bothrops viper envenomation. In this study, the nefrotoxicity of a main component of B. leucurus venom called L-aminoacid oxidase (LAAO-Bl) was evaluated by using tubular epithelial cell lines MDCK and HK-2 and perfused kidney from rats. LAAO-Bl exhibited cytotoxicity, inducing apoptosis and necrosis in MDCK and HK-2 cell lines in a concentration-dependent manner. MDCK apoptosis induction was accompanied by Ca 2+ release from the endoplasmic reticulum, reactive oxygen species (ROS) generation and mitochondrial dysfunction with enhanced expression of Bax protein levels. LAAO-Bl induced caspase-3 and caspase-7 activation in both cell lines. LAAO-Bl (10 μg/mL) exerts significant effects on the isolated kidney perfusion increasing perfusion pressure and urinary flow and decreasing the glomerular filtration rate and sodium, potassium and chloride tubular transport. Taken together our results suggest that LAAO-Bl is responsible for the nephrotoxicity observed in the envenomation by snakebites. Moreover, the cytotoxic of LAAO-Bl to renal epithelial cells might be responsible, at least in part, for the nephrotoxicity observed in isolated kidney.
    Full-text · Article · Jul 2015 · PLoS ONE
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    ABSTRACT: Bothropoides insularis (jararaca-ilhoa) is a native endemic snake limited to the specific region of Queimada Island, on São Paulo coast. Several local and systemic effects have been described due to envenomation caused by it, such as edema, tissue necrosis, hemorrhage and acute renal failure. Our previous studies have shown that Bothropoides insularis venom (BinsV) demonstrated important functional and morphologic alterations in rat isolated kidney, especially decrease in tubular electrolyte transport, osmotic clearance and tubular necrosis. In order to elucidate the direct nephrotoxicity mechanism, the aim of the present study was to investigate BinsV cytotoxicity effect on renal epithelial cells. The treatment with BinsV over MDCK culture decreased cell viability in all concentrations tested with IC50 of 9 μg/mL. BinsV was able to induce membrane rupture and cell death with phosphatidilserine externalization. Furthermore, BinsV induced ROS overproduction and mitochondrial membrane potential collapse, as well as Bax translocation and caspases 3 and 7 expression. Therefore, these events might be responsible by BinsV-induced cell death caused by mitochondrial dysfunction and ROS overproduction in the direct cytotoxicity process.
    No preview · Article · Sep 2014 · Toxicon
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    ABSTRACT: The p53 protein, a transcription factor with many gene targets, can also trigger apoptosis in the cytoplasm. The disruption of cell homeostasis, such as Ca(2+) signaling and mitochondrial respiration, contributes to the loss of viability and ultimately leads to cell death. However, the link between Ca(2+) signaling and p53 signaling remains unclear. During aging, there are alterations in cell physiology that are commonly associated with a reduced adaptive stress response, thus increasing cell vulnerability. In this work, we examined the effects of a cytoplasmic p53 inhibitor (pifithrin μ) in the striatum of young and aged rats by evaluating Ca(2+) signaling, mitochondrial respiration, apoptotic protein expression, and tissue viability. Our results showed that pifithrin μ differentially modulated cytoplasmic and mitochondrial Ca(2+) in young and aged rats. Cytoplasmic p53 inhibition appeared to reduce the mitochondrial respiration rate in both groups. In addition, p53 phosphorylation and Bax protein levels were elevated upon cytoplasmic p53 inhibition and could contribute to the reduction of tissue viability. Following glutamate challenge, pifithrin μ improved cell viability in aged tissue, reduced reactive oxygen species (ROS) generation, and reduced mitochondrial membrane potential (Δψm). Taken together, these results indicate that cytoplasmic p53 may have a special role in cell viability by influencing cellular Ca(2+) homeostasis and respiration and may produce differential effects in the striatum of young and aged rats.
    No preview · Article · Jul 2014 · Experimental Gerontology
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    ABSTRACT: Although the accumulation of the neurotoxic peptide β-amyloid (Aβ) in the central nervous system is a hallmark of Alzheimer's disease, whether Aβ acts in astrocytes is unclear, and downstream functional consequences have yet to be defined. Here, we show that cytosolic Ca2+ dysregulation, induced by a neurotoxic fragment (Aβ25–35), caused apoptosis in a concentration-dependent manner, leading to cytoplasmic Ca2+ mobilization from extra- and intracellular sources, mainly from the endoplasmic reticulum (ER) via IP3 receptor activation. This mechanism was related to Aβ-mediated apoptosis by the intrinsic pathway because the expression of pro-apoptotic Bax was accompanied by its translocation in cells transfected with GFP-Bax. Aβ-mediated apoptosis was reduced by BAPTA-AM, a fast Ca2+ chelator, indicating that an increase in intracellular Ca2+ was involved in cell death. Interestingly, the Bax translocation was dependent on Ca2+ mobilization from IP3 receptors because pre-incubation with xestospongin C, a selective IP3 receptor inhibitor, abolished this response. Taken together, these results provide evidence that Aβ dysregulation of Ca2+ homeostasis induces ER depletion of Ca2+ stores and leads to apoptosis; this mechanism plays a significant role in Aβ apoptotic cell death and might be a new target for neurodegeneration treatments.
    No preview · Article · May 2014 · European Journal of Neuroscience
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    ABSTRACT: Purpose: γ-rays (IR) cause an increase in intracellular calcium [Ca(2+)], alters contractility and triggers apoptosis via the activation of protein kinase C in intestinal guinea pig smooth muscle cells. The present study investigated the role of the mitochondria in these processes and characterized proteins involved in IR-induced apoptosis. Materials and methods: Intestinal smooth muscle cells were exposed to 10-50 Gy from a (60)Co γ-source. Reactive oxygen species (ROS) levels were measured by colourimetry with a fluorescente probe. Protein expression was analyzed by immunoblotting and immunofluorescence. Results: Apoptosis was inhibited by glutathione, possible by inhibiting the generation or scavenging ROS. Apoptosis was mediated by the mitochondria releasing cytochrome c leading to caspase 3 activation. IR increased the expression of the cyclins A, B2 and E and led to unbalanced cellular growth in an absorption dose-dependent manner. However, radiation did not induce alterations in the mitochondrial ultrastructure or in transmembrane electric potential. In contrast, IR increased the nuclear expression of cytoplasmic proteins and cyclins A and E. Conclusion: Smooth muscle cells subjected to IR undergo mitochondrial-mediated apoptosis that involves oncoproteins activation and preserves mitochondrial structure. IR also cause alterations in the expression and localization of both pro- and anti-apoptotic proteins.
    Full-text · Article · Apr 2014 · International Journal of Radiation Biology
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    ABSTRACT: Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca2+/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca2+ influx through voltage-dependent Ca2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders.
    Full-text · Article · Apr 2014 · Experimental Cell Research
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    ABSTRACT: Nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as an important modulator of Ca(2+) release from the endo-lysosomal system in a variety of cells by a new and ubiquitous class of endo-lysosomal ion channels known as the two-pore channels (TPCs). However, the role of TPCs in NAADP action in smooth muscle is not known. In the present work, we investigated the effects of NAADP in gastric smooth muscle cells and its ability to release Ca(2+) by TPCs. We show that Ca(2+) signals mediated by NAADP were inhibited by disrupting Ca(2+) handling by either acidic organelles (using bafilomycin A1) or the Endoplasmic Reticulum (using thapsigargin, ryanodine or 2-APB). Transcripts for endogenous TPC1 and TPC2 were readily detected and recombinant TPCs localized to the endosomes and/or lysosomes. Overexpression of wild-type TPCs but not pore mutants enhanced NAADP-mediated cytosolic Ca(2+) signals. Desensitizing the NAADP pathway inhibited Ca(2+)-responses to extracellular stimulation with carbachol but not ATP. Taken together, these results indicate that NAADP likely induces Ca(2+) release from the endolysosomal system through TPCs which is subsequently amplified via the ER in an agonist-specific manner. Thus, we suggest a second messenger role for NAADP in smooth muscle cells.
    No preview · Article · Apr 2014 · Cell Calcium
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    ABSTRACT: The search for new compounds that induce p53-independent apoptosis is the focus of many studies in cancer biology because these compounds could be more specific and would overcome chemotherapy resistance. In this study, we evaluated the in vitro antitumour activity of a Biphosphinic Palladacycle Complex (BPC) and extended preclinical studies to an in vivo model. Saos-2 cells, a p53-null human osteosarcoma drug-resistant cell line, were treated with BPC in the presence or absence of a cathepsin B inhibitor and a calcium chelator (CA074 and BAPTA-AM, respectively), and several parameters related to apoptosis were evaluated. Preclinical studies were performed with mice that were intravenously inoculated with murine melanoma B16F10-Nex2 cells and treated intraperitoneally (i.p.) with BPC (8 mg/kg/day) for ten consecutive days, when lung metastatic nodules were counted. In vitro data show that BPC induces cell death in Saos-2 cells mainly by apoptosis, which was accompanied by the effector caspase-3 activation. These events are most likely related to Bax translocation and increased cytosolic calcium mobilisation, mainly from intracellular compartments. Lysosomal Membrane Permeabilisation (LMP) was also observed after 12 h of BPC exposure. Interestingly, BAPTA-AM and CA074 significantly decreased BPC cytotoxicity, suggesting that both calcium and cathepsin B are required for BPC antitumour activity. In vivo studies demonstrated that BPC protects mice against murine metastatic melanoma. In conclusion, BPC complex is an effective anticancer compound against metastatic murine melanoma. This complex is cytotoxic to the drug-resistant osteosarcoma Saos-2 human tumour cells by inducing apoptosis triggered by calcium signalling and a lysosomal-dependent pathway.
    Full-text · Article · Mar 2014 · European Journal of Medicinal Chemistry
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    ABSTRACT: As the molecular mechanisms of Cytarabine, one of the most important drugs used in the leukaemia's treatment, are only partially understood and the role of autophagy on leukaemia development and treatment is only recently being investigated, in this study, by using Chloroquine (CQ) and 3-methyladenine (3MA) as autophagy inhibitors, we aim to evaluate the contribution of an autophagic mechanism to Cytarabine (AraC)-induced death of HL60 leukaemia cells. Trypan blue exclusion and AnnexinV/PI assays were used to evaluate HL60 cell death under AraC treatment in the presence or absence of 3MA and CQ. Western blotting and immunofluorescence experiments were performed to show the involvement of apoptosis and autophagy protein expressions. Phenotypic characterization of HL60-treated cells was performed by using immunophenotyping. Clonogenic assays were applied to analyse clonal function of HL60-treated cells. We observed that although autophagy inhibition by 3MA, but not CQ, increased the death of HL60 AraC cells after 24 h of treatment, no significant differences between AraC and AraC + 3MA-treated groups were observed by using clonogenic assay. In addition, increased number of immature (CD34(+)/CD38(-)Lin(-/low)) HL60 cells was found in AraC and AraC-3MA groups when compared with control untreated cells. Although AraC anti-leukaemia effects could be potentiated by 3MA autophagy inhibition after 24 h of exposure, leukaemia cell resistance, the main causes of treatment failure, is also promoted by autophagy initial stage impairment by 3MA, denoting the complex role of autophagy in leukaemia cells' response to chemotherapy.
    No preview · Article · Mar 2014 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: Significance: Aging is a multi-factorial process that may be associated with several functional and structural deficits which can evolve into degenerative diseases. In this review, we present data that may depict an expanded view of molecular aging theories, beginning with the idea that reactive oxygen species (ROS) are the major effectors in this process. In addition, we have correlated the importance of autophagy as a neuroprotective mechanism and discussed a link between age-related molecules, Ca(2+) signaling, and oxidative stress. Recent advances: There is evidence suggesting that alterations in Ca(2+) homeostasis, including mitochondrial Ca(2+) overload and alterations in electron transport chain (ETC) complexes, which increase cell vulnerability, are linked to oxidative stress in aging. As much as Ca(2+) signaling is altered in aged cells, excess ROS can be produced due to an ineffective coupling of mitochondrial respiration. Damaged mitochondria might not be removed by the macroautophagic system, which is hampered in aging by lipofuscin accumulation, boosting ROS generation, damaging DNA, and, ultimately, leading to apoptosis. Critical issues: This process can lead to altered protein expression (such as p53, Sirt1, and IGF-1) and progress to cell death. This cycle can lead to increased cell vulnerability in aging and contribute to an increased susceptibility to degenerative processes. Future directions: A better understanding of Ca(2+) signaling and molecular aging alterations is important for preventing apoptosis in age-related diseases. In addition, caloric restriction, resveratrol and autophagy modulation appear to be predominantly cytoprotective, and further studies of this process are promising in age-related disease therapeutics.
    No preview · Article · Feb 2014 · Antioxidants & Redox Signaling
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    ABSTRACT: Cited By (since 1996):4, Export Date: 18 October 2014
    No preview · Article · Jan 2014
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    ABSTRACT: Autophagy is a mechanism of protection against various forms of human diseases, such as cancer, in which autophagy seems to have an extremely complex role. In cancer, there is evidence that autophagy may be oncogenic in some contexts, whereas in others it clearly contributes to tumor suppression. In addition, studies have demonstrated the existence of a complex relationship between autophagy and cell death, determining whether a cell will live or die in response to anticancer therapies. Nevertheless, we still need to complete the autophagy-apoptosis puzzle in the tumor context to better address appropriate chemotherapy protocols with autophagy modulators. Generally, tumor cell resistance to anticancer induced-apoptosis can be overcome by autophagy inhibition. However, when an extensive autophagic stimulus is activated, autophagic cell death is observed. In this review, we discuss some details of autophagy and its relationship with tumor progression or suppression, as well as role of autophagy-apoptosis in cancer treatments.
    Full-text · Article · Oct 2013 · Chemico-biological interactions
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    ABSTRACT: Huntington's disease (HD) is a genetic neurodegenerative disorder that is characterized by severe striatal atrophy with extensive neuronal loss and gliosis. Although the molecular mechanism is not well understood, experimental studies use the irreversible mitochondrial inhibitor 3-nitropropionic acid (3-NP) to mimic the neuropathological features of HD. In this study, the role of autophagy as a neuroprotective mechanism against 3-NP-induced astrocyte cytotoxicity was evaluated. Autophagy is a catabolic process that is essential for the turnover of cytosolic proteins and organelles and is involved in the modulation of cell death and survival. We showed that 3-NP-induced apoptosis, which was accompanied by Bax and Beclin-1 upregulation, was dependent on acidic vesicular organelle (AVO) formation after a continuous exposure to 3-NP for 12 h. The upregulation of Bax and Beclin-1 as well as AVO formation were normalized 24 h after 3-NP exposure.
    No preview · Article · Oct 2013 · Neurochemical Research
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    ABSTRACT: It is well established that reduction of Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (L-type VDCC), or increase of cytosolic cAMP concentration ([cAMP]c), inhibit contractile activity of smooth muscles in response to transmitters released from sympathetic nerves. Surprisingly, in this work we observed that simultaneous administration of L-type VDCC blocker (verapamil) and [cAMP]c enhancers (rolipram, IBMX and forskolin) potentiated purinergic contractions evoked by electrical field stimulation of rat vas deferens, instead of inhibiting them. These results, including its role in sympathetic transmission, can be considered as a "calcium paradox". On the other hand, this potentiation was prevented by reduction of [cAMP]c by inhibition of adenylyl cyclase (SQ 22536) or depletion of Ca(2+) storage of sarco-endoplasmic reticulum by blockade of Ca(2+) reuptake (thapsigargin). In addition, cytosolic Ca(2+) concentration ([Ca(2+)]c) evaluated by fluorescence microscopy in rat adrenal medullary slices was significantly reduced by verapamil or rolipram. In contrast, simultaneous incubation of adrenal slices with these compounds significantly increased [Ca(2+)]c. This effect was prevented by thapsigargin. Thus, a reduction of [Ca(2+)]c due to blockade of Ca(2+) influx through L-type VDCC could stimulate adenylyl cyclase activity increasing [cAMP]c thereby stimulating Ca(2+) release from endoplasmic reticulum, resulting in augmented transmitter release in sympathetic nerves and contraction.
    Full-text · Article · Jul 2013 · Cell calcium
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    ABSTRACT: To verify if the medicinal plants Panax ginseng C.A. Mey, Turnera diffusa Willd. ex Schult., and Heteropterys tomentosa O. Mach., which are amply used by the population as tonics and cognition enhancers, could have a protective effect on cell death by apoptosis, since this could be one of the mechanisms of action of these substances. Aged male Wistar rats (n=24) were divided into four groups. Over 30 days, three groups received treatments with hydroalcoholic extracts of the plants, and one group received saline solution. A fifth group with young adult male Wistar rats (n=4) received saline solution during the same period. Using the TUNEL technique, the percentage of apoptosis in the hippocampus of these animals was evaluated. No differences were observed between the percentage of apoptotic cells in the hippocampus of aged animals and of young control animals. The percentage of apoptosis in the hippocampus of aged animals treated chronically with the extracts from the three plants also did not differ from the percentage of apoptosis in the hippocampus of the control group of aged animals. Treatment with the hydroalcoholic extracts of Panax ginseng, Turnera diffusa, and Heteropterys tomentosa did not influence the apoptosis of the hippocampal cells of aged rats.
    Full-text · Article · Jun 2013 · Einstein (São Paulo
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    ABSTRACT: Enhanced activity of the sympatho-adrenal axis and augmented circulating catecholamines has been implicated in the development of hypertension. Release of catecholamine from stimulated adrenal medulla chromaffin cells has been shown to be higher and longer in spontaneously hypertensive rats (SHRs), compared with normotensive Wistar rats (NWRs). Whether differences in the functional expression of voltage-dependent calcium channels (VDCCs) of the L-, N-, or P/Q subtypes may contribute to such distinct secretory behaviour, is unknown. We therefore approached here this study in voltage-clamped NWR and SHR chromaffin cells, using 10mM Ba(2+) as charge carrier (IBa) and selective blockers of each channel type. We found that compared with NWR cells, SHR chromaffin cells exhibited the following differences: (1) 30% diminution of the IBa fraction carried by L channels; (2) a doubling of the IBa fraction carried by P/Q channels; (3) more visible current modulation by ATP that could be linked to a 10-fold higher mRNA levels for purinergic receptors of the P2Y2 subtype; and (3) a higher contribution of PQ channels to the transients of the cytosolic calcium concentrations ([Ca(2+)]c) generated by K(+), compared with L channels. These results may contribute to the better understanding of the greater calcium signalling and exocytotic responses of SHR compared with NWR chromaffin cells, found in three previous reports from our laboratories.
    Full-text · Article · Mar 2013 · European journal of pharmacology

Publication Stats

3k Citations
265.78 Total Impact Points

Institutions

  • 1998-2015
    • Universidade Federal de São Paulo
      • Departamento de Farmacologia
      San Paulo, São Paulo, Brazil
  • 2012
    • University of Michigan
      • Life Sciences Institute
      Ann Arbor, MI, United States
  • 1999
    • National Institutes of Health
      • Section on Molecular Signal Transduction
      Maryland, United States