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Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats 下载免费PDF全文
Hassan I El-Sayyad Mohamed F Ismail F M Shalaby RF Abou-El-Magd Rajiv L Gaur Augusta Fernando Madhwa HG Raj Allal Ouhtit 《International journal of biological sciences》2009,5(5):466-473
Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs. 相似文献
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Joana RF Abreu Daphne de Launay Marjolein E Sanders Aleksander M Grabiec G Marleen van de Sande Paul P Tak Kris A Reedquist 《Arthritis research & therapy》2009,11(4):R121-13
Introduction
Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases (MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to contribute to inflammation and joint destruction in RA, and abrogation of Ras family signaling is therapeutic in animal models of RA. Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. Here, we examine the potential relationship between RasGRF1 expression and MMP production in RA, reactive arthritis, and inflammatory osteoarthritis synovial tissue and FLS. 相似文献4.
Viability selection and fecundity of size-related traits has been demonstrated to be strong in vertebrates. In small mammals,
both offspring and adult size are important for viability and fecundity, respectively. We studied the role of early phenotypic
selection on size attributes and female fecundity in the leaf-eared mouse (Phyllotis darwini). Our results support that larger females produce more offspring, and since the likelihood of attaining adulthood is similar
for different sizes of the females, those larger females also produce more offspring that attain sexual maturity. From the
offspring perspective, larger pups at birth have significantly more probability of attaining sexual maturity. However, weaning
mass and growth rate did not show any differential survival. Our study suggests that early selection could be important and
could prevent further episodes of selection by early culling of the distribution of sizes, and that “effective” fecundity
is strongly dependent on the size of the female. 相似文献
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Roberto F. Nespolo Fabien Halkett Christian C. Figueroa Manuel Plantegenest Jean-Christophe Simon 《Evolution; international journal of organic evolution》2009,63(9):2402-2412
Life‐history theory postulates that evolution is constrained by trade‐offs (i.e., negative genetic correlations) among traits that contribute to fitness. However, in organisms with complex life cycles, trade‐offs may drastically differ between phases, putatively leading to different evolutionary trajectories. Here, we tested this possibility by examining changes in life‐history traits in an aphid species that alternates asexual and sexual reproduction in its life cycle. The quantitative genetics of reproductive and dispersal traits was studied in 23 lineages (genotypes) of the bird cherry‐oat aphid Rhopalosiphum padi, during both the sexual and asexual phases, which were induced experimentally under specific environmental conditions. We found large and significant heritabilities (broad‐sense) for all traits and several negative genetic correlations between traits (trade‐offs), which are related to reproduction (i.e., numbers of the various sexual or asexual morphs) or dispersal (i.e., numbers of winged or wingless morphs). These results suggest that R. padi exhibits lineage specialization both in reproductive and dispersal strategies. In addition, we found important differences in the structure of genetic variance–covariance matrices ( G ) between phases. These differences were due to two large, negative genetic correlations detected during the asexual phase only: (1) between fecundity and age at maturity and (2) between the production of wingless and winged parthenogenetic females. We propose that this differential expression in genetic architecture results from a reallocation scheme during the asexual phase, when sexual morphs are not produced. We also found significant G × E interaction and nonsignificant genetic correlations across phases, indicating that genotypes could respond independently to selection in each phase. Our results reveal a rather unique situation in which the same population and even the same genotypes express different genetic (co)variation under different environmental conditions, driven by optimal resource allocation criteria. 相似文献
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The ability of organisms to perform at different temperatures could be described by a continuous nonlinear reaction norm (i.e., thermal performance curve, TPC), in which the phenotypic trait value varies as a function of temperature. Almost any shift in the parameters of this performance curve could highlight the direct effect of temperature on organism fitness, providing a powerful framework for testing thermal adaptation hypotheses. Inter-and intraspecific differences in this performance curve are also reflected in thermal tolerances limits (e.g., critical and lethal limits), influencing the biogeographic patterns of species’ distribution. Within this context, here we investigated the intraspecific variation in thermal sensitivities and thermal tolerances in three populations of the invasive snail Cornu aspersum across a geographical gradient, characterized by different climatic conditions. Thus, we examined population differentiation in the TPCs, thermal-coma recovery times, expression of heat-shock proteins and standard metabolic rate (i.e., energetic costs of physiological differentiation). We tested two competing hypotheses regarding thermal adaptation (the “hotter is better” and the generalist-specialist trade-offs). Our results show that the differences in thermal sensitivity among populations of C. aspersum follow a latitudinal pattern, which is likely the result of a combination of thermodynamic constraints (“hotter is better”) and thermal adaptations to their local environments (generalist-specialist trade-offs). This finding is also consistent with some thermal tolerance indices such as the Heat-Shock Protein Response and the recovery time from chill-coma. However, mixed responses in the evaluated traits suggest that thermal adaptation in this species is not complete, as we were not able to detect any differences in neither energetic costs of physiological differentiation among populations, nor in the heat-coma recovery. 相似文献
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Artacho P Soto-Gamboa M Verdugo C Nespolo RF 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,147(4):1060-1066
Living organisms are continuously faced with several forms of environmental perturbation, one of the most important being human activity. In this scenario, the role of physiological studies on wildlife has proved to be important given that in vivo physiological variables reflect a great deal how sensitive animals are to acute environmental changes. We studied the haematological parameters in black-necked swans (Cygnus melanocoryphus) at the Ramsar site at the Carlos Anwandter Sanctuary, which were experiencing a drastic population decrease. Through seven months, body mass (body mass corrected by total length) was reduced 30%, which was followed by significant reductions of haemoglobin concentration, haematocrit and red blood cell count. Mean cell volume and mean cell haemoglobin concentration did not change with time, whereas there was a significant increase of the white blood cells and heterophile / lymphocyte ratio. Our results, together with the published evidence, suggests that the proximal factors associated with the mass mortality and emigration of the black - necked swan population at the "Carlos Anwandter Sanctuary" was a drastic nutritional deficiency, and the potentially toxic effects of iron pollution in the waters of the Ramsar site. 相似文献
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Nespolo RF Artacho P Verdugo C Castañeda LE 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2008,150(3):366-368
Avian bioenergetic studies suggest that, compared with other vertebrates, birds are efficient thermoregulators. However, most avian physiological studies have been performed in species of small body masses (less than 1 kg). In contrast to what might be anticipated, thermoregulatory abilities of large, flying birds are scarcely studied, especially in temperate zones and aquatic systems. In order to determine short-term metabolic adjustment after thermal challenge, we studied the bioenergetics of a South American anseriform, the black-necked swan (Cygnus melanocoryphus). Our results suggest that this swan species exhibits lower resting metabolic rate compared with other anseriforms, and some hetherothermia. In addition, the black-necked swans in our study changed "wet" thermal conductance at different ambient temperatures. At our working Ta range (5, 10, 15, 20 and 25 degrees C) calculated values were considerably higher than expected (23%, 26%, 39% and 51% higher than expected, respectively). Our results differ considerably from the only two previous reports in swan species, suggesting that C. melanocoryphus, perhaps due to its temperate distribution, is more sensitive to changes in environmental temperature. 相似文献
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