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Living Donor Liver Transplantation (LDLT) is a promising approach to treating end-stage liver diseases, however, some post-operatory complications such as pneumonia, bacteremia, urinary tract infections, and hepatic dysfunction have been reported. In murine models using partial hepatectomy (PHx), a model that emulates LDLT, it has been determined that the synthesis of hepatic cell proliferation factors that are associated with noradrenaline synthesis are produced in locus coeruleus (LC). In addition, studies have shown that PHx decreases GABA and 5-HT2A receptors, promotes loss of dendritic spines, and favors microgliosis in rat hippocampus. The GABA and serotonin-altered circuits suggest that catecholaminergic neurons such as dopamine and noradrenaline neurons, which are highly susceptible to cellular stress, can also be damaged. To understand post-transplant affections and to perform well-controlled studies it is necessary to know the potential causes that explain as a liver surgical procedure can produce brain damage. In this paper, we review several cellular processes that could induce gliosis in LC after rat PHx.
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Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Masculino , Animais , Ratos Wistar , Bromodesoxiuridina/farmacologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologiaRESUMO
PURPOSE: The main goal of this study was to determine the relationship of cleaved-caspase-3 (C3)-related apoptosis and hepatic proliferation, during the liver repopulation in a living liver donor rat model. MATERIAL/METHODS: Thirty-three animals were randomized into eleven groups and evaluated on postoperative from 3 âh until 384 âh after 30%-partial hepatectomy (30%-PHx). Liver sections (5 âµm) were processed by hematoxylin-eosin, and immunostaining for C3, accompanied by hepatic function test. C3 content and the hepatic lobule enlargement were analyzed by optical density, followed by cell counting. RESULTS: Transient variations of alanine transferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were found. Significant increase in the C3 levels, and cell nuclei number, were detected at 12 âh and 48 âh after 30%-PHx, evidencing a correlation of p â= â-0.3679. CONCLUSION: In the 30%-PHx rat model, C3-related apoptosis prevents proliferative pathological conditions during the hepatic lobule re-modeling.
Assuntos
Apoptose , Caspase 3/metabolismo , Proliferação de Células , Hepatectomia/métodos , Regeneração Hepática , Fígado/patologia , Animais , Caspase 3/genética , Doadores Vivos/estatística & dados numéricos , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVES: Cassava (Manihot esculenta Crantz) contains cyanogenic glycosides (linamarin and lotaustralin) that have been associated with neurological disorders in humans and rats. In basal ganglia, the dopaminergic neurons of substantia nigra pars compacta (SNpc) show high cytotoxic susceptibility; therefore, the chronic consumption of cassava (CCC) could induce neurodegeneration in SNpc. In this study we examine the impact of CCC on the integrity of the nigrostriatal system, including apoptosis and microgliosis. MATERIALS AND METHODS: Male Wistar rats were administered cassava juice daily (3.57 g/kg and 28.56 g/kg, per os) or linamarin (0.15 mg/ml, IP), and its effects were evaluated in rota-rod and swim tests at days 7, 14, 21, 28, and 35 of administration. In SNpc, oxidative/nitrosative stress was determined by malondialdehyde/4-hydroxyalkenals (MDA-4-HAD) and nitrite contents. Tyrosine hydroxylase immunoreactivity (TH-IR) was evaluated in SNpc, neostriatum (NE), and nucleus accumbens (NA). Apoptosis and microgliosis were determined by active-caspase-3 (C3) and CD11b/c (OX42) expression in the medial region of SNpc. RESULTS: Chronic administration of cassava juice, or linamarin, increased motor impairment. The rats that received 28.56 g/kg cassava showed increased MDA-4-HAD content in SNpc and nitrite levels in NE with respect to controls. Significant loss of TH-IR in SNpc, NE, and NA was not found. The 28.56 g/kg cassava administration produced dopaminergic atrophy and microgliosis, whereas linamarin induced hypertrophy and C3-related apoptosis in SNpc. CONCLUSION: CCC induces cellular stress on dopaminergic neurons, which could contribute to motor impairment in the rat.
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The efficient extraction and fixation of a tissue allows in preserving the cytoarchitecture, chemical composition and tissue organization, which is key in physiological and histopathological studies. The main goal of this study was to establish a microsurgery technique to obtain ocular tissue and provide an optimized immersion fixation protocol based on the 10 % formalin-intraocular injection on Olive ridley sea turtle hatchlings (Lepidochelys olivacea). To evaluate this optimized technique, a histological comparison between traditional immersion and intraocular/immersion protocols was done. The eyeball were processed into five protocols: Frozen eyes (Group 1), frozen eyes immersed in 10 % formalin (Group 2), fresh eyes immersed in 10 % formalin (Group 3), fresh eyes intraocularly injected with 0.1 M phosphate buffer solution (PBS) and then immersed in 10 % formalin (Group 4), and fresh eyes fixed by 10 % formalin-intraocular followed by 10 % formalin-immersion (Group 5). In comparison with all groups evaluated, the intraocular/immersion fixation protocol lead the conservation of eyeball shape, cell integrity and maintenance of the organization of the retina layers of sea turtle hatchlings. If this method will be the key in studying sea turtle, we suppose that this procedure, with minimal adjustments, could be useful in animals with similar eye anatomy.