Navegando por Palavras-chave "doxorubicin"
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- ItemSomente MetadadadosAmifostine-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 UnivIn 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.
- ItemAcesso aberto (Open Access)Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxorubicin-treated rats(Wiley, 2018) Cabral, R. E. L. [UNIFESP]; Mendes, T. B. [UNIFESP]; Vendramini, V. [UNIFESP]; Miraglia, S. M. [UNIFESP]Doxorubicin has been largely used in anticancer therapy in adults, adolescents, and children. The efficacy of l-carnitine as an antioxidant substance has been confirmed both in humans and rats. Carnitine, present in testis and epididymis, is involved in sperm maturation. It is also effective in infertility treatment. As a continuation of a previous study, we evaluated whether some spermatic qualitative parameters, DNA integrity, chromatin structure, and fertility status, could be ameliorated by the carnitine treatment in adult rats, which were subsequently exposed to doxorubicin at pre-puberty. Pre-pubertal male rats were distributed into four groups: Sham Control
- ItemSomente MetadadadosCarnitine partially protects the rat testis against the late damage produced by doxorubicin administered during pre-puberty(Wiley-Blackwell, 2014-11-01) Cabral, R. E. L. [UNIFESP]; Okada, F. K. [UNIFESP]; Stumpp, Taiza [UNIFESP]; Vendramini, V. [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Doxorubicin, an anticancer drug, is widely included in chemotherapy protocols to combat childhood cancer. Carnitine, an important quaternary amine, is present in testis and epididymis and is involved in sperm maturation; it has been used in infertility treatment. in a previous study, our group observed that l-carnitine given before etoposide, another chemotherapeutic drug, reduces the spermatogenic damage and protects germ cells against apoptosis. This study aimed to evaluate the antiapoptotic and cytoprotective actions of l-carnitine in long- and mid-term basis, on the seminiferous epithelium of doxorubicin-treated pre-pubertal rats. Forty-eight 30-day-old male Wistar rats were distributed into four groups: sham-control; doxorubicin; carnitine; carnitine/doxorubicin (l-carnitine injected 1h before doxorubicin). the rats were submitted to euthanasia at 64 and 100days of age and their testes were collected for biometric, morphometric, and histopathological analyses. the numerical density of apoptotic germ cells was obtained (TUNEL method). in adult phase (100days), the following spermatic parameters were analyzed: mature spermatid (19 step) count and sperm daily production per testis; sperm number and transit time through the epididymal caput/corpus and cauda; frequency of morphologically abnormal spermatozoa (from epididymal fluid), as well as sperm DNA integrity (Comet assay). the testicular and spermatic parameters at both ages were improved in rats treated with carnitine before doxorubicin. At 64days, the TUNEL-positive germ cell frequency was lower in the carnitine/doxorubicin-treated rats comparatively to the doxorubicin-treated rats. At 100days of age, the sperm DNA fragmentation was also lower in the previously carnitine-treated rats, as evidenced by the analysis of three parameters. Carnitine reduced the late testicular and spermatic damages caused by doxorubicin, probably providing a partial cytoprotection against the deleterious action of doxorubicin administration to pre-pubertal rats. However, further studies shall be undertaken to investigate the protective mechanisms involved in such germ cell preservation.
- ItemAcesso aberto (Open Access)Função sistólica do ventrículo esquerdo pela ecocardiografia em crianças e adolescentes com osteossarcoma tratados com doxorrubicina com e sem dexrazoxane(Sociedade Brasileira de Cardiologia - SBC, 2006-12-01) Matos Neto, Ranulfo Pinheiro de [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Silva, Célia Maria Campos [UNIFESP]; Campos Filho, Orlando [UNIFESP]; Oporto, Victor Manuel [UNIFESP]; Gomes, Lourdes de Fátima Gonçalves [UNIFESP]; Paiva, Marcelo Goulart [UNIFESP]; Carvalho, Antonio Carlos [UNIFESP]; Moisés, Valdir Ambrósio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To evaluate left ventricular (LV) systolic function by means of echocardiography in patients with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane. METHODS: The study analyzed 55 patients with osteosarcoma, with or without metastasis, undergoing a six-cycle chemotherapy regimen of doxorubicin, who were divided into two groups according to dexrazoxane use. Group I: Thirty-seven patients who did not receive dexrazoxane (28 males, average age 15.4 years). Group II: Eighteen patients who did receive dexrazoxane (15 males, average age 15.1 years). Four echocardiographic evaluations were performed: 1) before the beginning of the chemotherapy (initial evaluation); 2) up to two weeks after the third cycle; 3) up to two weeks after the fifth cycle; and 4) up to four weeks after the sixth cycle of chemotherapy (final evaluation). The left ventricular systolic function was assessed by the fractional percentage of systolic shortening (FS%) on echocardiography. Alterations in the contractile function or cardiac toxicity were defined as FS% values equal to or lower than 29%, and/or by a drop in FS% by an absolute value equal to or greater than 10 units of the baseline value of each patient. RESULTS: No significant difference as to age, gender, and race was observed between the groups. The cumulative dose of doxorubicin was significantly higher in group II throughout all phases of the treatment: 174 x 203 mg/m²; 292 x 338 mg/m² and 345 x 405 mg/² (p < 0.0001). According to previously established criteria, the incidence of LV systolic dysfunction was not significantly different (p=0.248) between patients in group I (18.92%) and patients in group II (11.1%). The variance analysis with repeated measurements did not show significant differences in the means of fractional percentage of systolic percentage (FS%) throughout the study (p=0.967). However, a significant difference (p=0.029) was observed between the FS% means in groups I and II at evaluations 2 (35.67 x 37.21%), 3 (34.95 x 38.47%) and 4 (35.26 x 38.22%). CONCLUSION: Data in this study show that in patients with osteosarcoma treated with doxorubicin alone or combined with dexrazoxane, the LV systolic function, as assessed by the fractional percentage of systolic shortening mean, showed a better performance in the group that received dexrazoxane. On the other hand, the occurrence of systolic dysfunction was similar in both groups.
- ItemAcesso aberto (Open Access)Metformin Mitigates Fibrosis and Glucose Intolerance Induced by Doxorubicin in Subcutaneous Adipose Tissue(Frontiers Media Sa, 2018) Biondo, Luana A.; Batatinha, Helena A.; Souza, Camila O.; Teixeira, Alexandre A. S.; Silveira, Loreana S.; Alonso-Vale, Maria Isabel C. [UNIFESP]; Oyama, Lila Missae [UNIFESP]; Alves, Michele J.; Seelaender, Marilia [UNIFESP]; Neto, Jose C. R.Doxorubicin (DX) is a chemotherapeutic drug that is used in clinical practice that promotes deleterious side effects in non-tumor tissues such as adipose tissue. We showed that DX leads to extensive damage in adipose tissue via a disruption in 5'-adenosine monophosphate-activated protein kinase (AMPK) and PPAR-gamma signaling. Thus, we investigated whether co-treatment with the biguanide drug metformin (MET) could prevent the side effects of DX through the activation of AMPK in adipose tissue. The goal of the present study was to verify the effects of DX and adjuvant MET treatment in subcutaneous adipose tissue (SAT) and to determine whether MET could protect against chemotherapy-induced side effects. C57/BL6 mice received DX hydrochloride (2.5 mg/kg) intraperitoneally 2 times per week for 2 weeks (DX), concomitantly or not, with MET administration (300 mg/kg oral daily) (DX + MET). The control group (CTRL) was pair-fed according to the food consumption of the DX group. After euthanasia, adipose tissue fat pads were collected, and SAT was extracted so that adipocytes could be isolated. Glucose uptake was then measured, and histological, gene, and protein analyses were performed. One-way analysis of variance was also performed, and significance was set to 5%. DX reduced retroperitoneal fat mass and epididymal pads and decreased glycemia. In cultured primary subcutaneous adipocytes, mice in the DX group had lower glucose uptake when stimulated with insulin compared with mice in the CTRL group. Adipocytes in the DX group exhibited a reduced area, perimeter, and diameter