Histopathology of mammary tumours in female rats treated with 1-methyl-1-nitrosourea.
ABSTRACT To induce, evaluate and classify advanced stages of mammary gland tumours induced by MNU.
Female Sprague-Dawley rats were injected intraperitoneally with 1-methyl-1-nitrosourea (MNU; 50 mg.kg-1) on the day 33, 40, 47, 54 and 61 of age in the first experiment and on 50th and 113th day in the second experiment. On the 117th day (first experiment) and on the 153rd day of age (second experiment) the rats were sacrificed by decapitation and their mammary glands were evaluated both macroscopically and microscopically for the presence of grossly detectable mammary tumours. Mammary tumours were classified according to Russo et al. (1990).
The final incidence of palpable carcinomas was ranging from 60 % to 76 %. All microscopically evaluated tumours were malignant. Among the total number of lesions classified the percentage of invasive tumours ranged from 35 % to 44 %. No metastases were observed in other organs in MNU treated animals.
- SourceAvailable from: Aleksandar Djordjevic
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- "All 32 rats received i.p. applications of MNU (50 mg/kg of body weight) (carcinogenicity was induced chemically) on the 50th and 113th day of age . On the 160th day of age, the rats were treated with Dox and/or Full. "
ABSTRACT: The aim of this study was to investigate the potential protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8mg/kg), doxorubicin/fullerenol (100mg/kg of fullerenol 30min before administration of 8mg/kg doxorubicin) and fullerenol (100mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12h, 24h, 48h and 96h at concentrations of 10microg/mL and 44microg/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1microm; 5microm) and fullerenol (10microg/mL; 44microg/mL) in different combinations. When the cells are treated with 5microm doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound.Biomaterials 08/2008; 29(24-25):3451-60. DOI:10.1016/j.biomaterials.2008.04.048 · 8.31 Impact Factor
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ABSTRACT: Oxidative stress has an important role in the pathogenesis of doxorubicin (DOX)-induced nephrotoxicity. The aim of this study was to investigate the nephroprotective effects of fullerenol (FLR), an antioxidant agent, on DOX-induced nephrotoxicity. The investigation was carried out on adult female Sprague Dawley outbred rats with chemically induced breast cancer (1-methyl-1-nitrosourea; 50 mg/kg; ip). Rats were divided into the following groups: control healthy, control cancer, DOX alone (8 mg/kg, ip, cancer), DOX plus FLR as a pre-treatment (8 mg/kg and 100 mg/kg, respectively, ip, cancer), and FLR alone (100 mg/kg, ip, cancer). At the end of the 2nd day after drug administration, blood and kidney tissues were taken for analysis. The activity of lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase as serum enzymes, as well as level of malondialdehyde, glutathione, glutathione peroxidase, glutathione reductases, catalase and superoxide dismutase, were determined. DOX caused nephrotoxicity, but FLR pre-treatment prevented oxidative stress, lipid peroxidation and the disbalance of GSH/GSSG levels in kidney tissue caused by DOX. Our results confirm satisfactory nephroprotective efficacy of FLR in the acute phase of toxicity and encourage further studies regarding its use as a potential nephroprotector.Pharmacological reports: PR 11/2007; 60(5):742-9. · 2.17 Impact Factor
- American Journal of Infection Control 09/2002; 30(5):318-9. DOI:10.1067/mic.2002.127205 · 2.33 Impact Factor