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他莫昔芬诱导糖尿病和非糖尿病雌性Wistar大鼠发生肝脏铁过载。

Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats.

作者信息

Jatobá Carlos André Nunes, de Rezende Adriana Augusto, de Paiva Rodrigues Sarah Jane, de Almeida Câmara Maria Margareth, das Graças Almeida Maria, Freire-Neto Francisco, da Rocha Luiz Reginaldo Menezes, da Medeiros Aldo Cunha, Brandão-Neto José, de Carvalho Formiga Maria Célia, de Azevedo Italo Medeiros, de Oliveira Ramos Ana Maria

机构信息

Postgraduate Course in Health Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil.

出版信息

Biometals. 2008 Apr;21(2):171-8. doi: 10.1007/s10534-007-9105-8. Epub 2007 Jul 17.

Abstract

Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.

摘要

他莫昔芬(TX)是一种用于治疗乳腺癌的药物,可能会使一些患者出现肝脏变化。其对患有或未患糖尿病(DM)的大鼠肝脏组织的影响尚未得到充分研究。本研究的目的是评估血浆肝酶水平与使用TX的链脲佐菌素诱导的DM雌性Wistar大鼠肝组织中铁过载之间的相关性。在对照组中对雌性大鼠进行研究:C-0(未使用药物)、C-V(仅使用山梨醇载体)和C-TX(使用TX)。DM组(糖尿病未使用药物)和DM-TX组(糖尿病使用TX)为试验组。诱导DM 60天后,采集血样检测血糖、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)和胆红素。对肝组织切片进行苏木精-伊红染色、Masson三色染色、普鲁士蓝染色处理。通过原子吸收光谱法定量肝铁含量。DM组和DM-TX组的AST、ALT和ALP水平显著升高,胆红素水平无变化。仅在C-TX组和DM-TX组中观察到使用普鲁士蓝染色和原子吸收光谱法检测的肝脏铁过载。DM-TX组中AST、ALT和ALP水平与肝脏显微镜下铁沉积强度呈正相关。总之,在糖尿病和非糖尿病大鼠中,TX给药与肝脏铁沉积有关。此外,TX在非糖尿病大鼠中诱导肝脏铁过载且肝功能未改变,可能是研究铁代谢生物调控的有用工具。

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