Navegando por Palavras-chave "amifostine"

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    Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo
    (Wiley-Blackwell, 2002-11-01) Segreto, Helena Regina Comodo [UNIFESP]; Ferreira, Alice Teixeira [UNIFESP]; Kimura, Edna Teruko [UNIFESP]; Franco, Marcello [UNIFESP]; Egami, Mizue Imoto [UNIFESP]; Silva, Maria Regina Regis da [UNIFESP]; Segreto, Roberto Araujo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Experiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. in amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo. (C) 2002 Wiley-Liss, Inc.
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    Amifostine protective effect on cisplatin-treated rat testis
    (Wiley-Blackwell, 2008-07-01) Lirdi, Leandra Campos [UNIFESP]; Stumpp, Taiza [UNIFESP]; Sasso-Cerri, Estela; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); São Paulo State Univ
    Cisplatin is a potent drug used in clinical oncology but causes spermatogenesis damage. Amifostine is a drug used against toxicity caused by ionizing irradiation and chemotherapeutic drugs. Since cisplatin provokes fertility and induces germ cell apoptosis and necrosis, we proposed to evaluate the amifostine cytoprotective action on testes of cisplatin-treated rats. Thirty-day-old prepubertal Wistar rats received a single cisplatin dose of 5 mg/kg and were killed after 3, 6, and 12 hr. the hematoxylin-eosin stained testicular sections were submitted to histological, morphometric, and stereological analysis. the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) method was used to label apoptotic cells. TUNEL-positive and TUNEL-negative germ cells with abnormal nuclear morphology (ANM) were scored. Significant alterations of greater part of the parameters occurred in the cisplatin-treated group (CE) compared to the group that received amifostine before the cisplatin-treatment (ACE); however, testicular weight and volume did not vary between these groups. Tubular diameter was reduced in CE in comparison to ACE rats, while interstitial tissue and lymphatic space volume and volume density were significantly higher in CE rats; interstitial testicular edema probably occurred in cisplatin-treated rats. CE rats showed important histological alterations, which were more accentuated than in ACE rats. the numerical densities of apoptotic germ cells and TUNEL-negative cells with ANM were lower in ACE than in CE rats. in conclusion, the amifostine previously administered to prepubertal rats reduced the testicular damage caused by cisplatin. We conclude that amifostine partially protected the rat seminiferous epithelium against cisplatin toxicity.
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    Amifostine-doxorubicin association causes long-term prepubertal spermatogonia DNA damage and early developmental arrest
    (Oxford Univ Press, 2012-08-01) Vendramini, V. [UNIFESP]; Robaire, B.; Miraglia, S. M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); McGill Univ
    In a previous study, we found that amifostine provides some protection to the seminiferous epithelium of prepubertal doxorubicin-treated male rats but does not improve their fertility status as adults. Based on these results, a long-term study was undertaken to evaluate the DNA damage caused to spermatogonia and the consequences for embryo development.Twenty-four male prepubertal rats (30-day-old) were divided into four equal groups and treated with: doxorubicin (D5 mg/kg), amifostine (A400 mg/kg), amifostine/doxorubicin (ADamifostine 15 min before doxorubicin) and control (C0.9 saline solution). Sixty-four days after the treatment, animals were euthanized and the testes and epididymides were excised. the testes were fixed in Bouins solution and historesin-embedded for histopathological analysis. Spermatozoa from the cauda epididymides were collected for chromatin structure analyses (Comet Assay and SCSA). Adult rats (100-day-old) were mated with fertile females for embryo analyses on 2.5, 4.5 and 20 days post-coitum (d.p.c.).The seminiferous epithelium histopathology of AD group was better preserved compared with the D group. On the other hand, rats from the D and AD groups presented an increased percentage of sperm DNA strand breaks, as assessed by the comet assay, as well as an increased level of sperm chromatin denaturation, as assessed by the SCSA assay. in amifostine-treated groups (A and AD) there was a significant increase in the number of arrested embryos, as observed by the number of oocytes/zygotes on 2.5 d.p.c., when compared with control and doxorubicin groups; however, this number was increased when the AD group was compared with the A group.These results raise a concern about the effects of the association of these two drugs on the germ cell genome. Amifostinedoxorubicin-exposed rat spermatogonia produced long-term damage on sperm DNA, compromised conceptus development and reduced pregnancy outcome.