Protective effect of fullerenol nano particles on colon cancer development in dimethylhydrazine rat model (original) (raw)
Related papers
Digest Journal of Nanomaterials and Biostructures
Colorectal cancer (CRC) is one of the most common cancers world-wide, with highest incidence rates in western countries. In recent years, much effort has been dedicated in search for natural or pharmacological preventive agents, which would block or attenuate CRC process. In search for new pharmacological agent, the effects of fullerenol C60(OH)24 nano particles (FNP) on liver oxidative status and promotion or progression phase of colorectal carcinogenesis in dimethylhydrazine-induced rat model of CRC were investigated. Our results demonstrate that FNP effectively inhibited formation of dysplastic aberrant crypt foci, which are regarded as early histopathological lesions in the pathogenesis of CRC. FNP treatment also improved activity of antioxidant enzymes in the liver. Since this was the first study investigating FNP effects on colon carcinogenesis further studies are needed to evaluate its protective effect also in other phases of carcinogenesis and to investigate whether its inh...
Protective effects of orally applied fullerenol nanoparticles in rats
Polyhydroxylated, water soluble, fullerenol C 60 (OH) 24 nano particles (FNP) in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX) (8 mg/kg (i.p.)) 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP), in H 2 O:dimethyl sulfoxide (DMSO) (80:20, w/w) solution given orally in final doses of 10, 14.4, and 21.2 mg/kg, three days successively, has the protective (hepatoprotective and nephroprotective) effect against doxorubicin-induced cytotoxicity via its antioxidant properties.
Hemijska industrija, 2011
Polyhydroxylated, water soluble, fullerenol C 60 (OH) 24 nano particles (FNP) in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX) (8 mg/kg (i.p.)) 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP), in H 2 O:dimethyl sulfoxide (DMSO) (80:20, w/w) solution given orally in final doses of 10, 14.4, and 21.2 mg/kg, three days successively, has the protective (hepatoprotective and nephroprotective) effect against doxorubicin-induced cytotoxicity via its antioxidant properties.
Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats
Experimental and molecular pathology, 2017
Doxorubicin (DOX), commonly used antineoplastic agent, affects bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects. Main mechanism of its toxicity is the production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential FNP protective role against DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into five groups: (1) 0.9% NaCl (control), (2) 100mg/kg ip FNP, (3) 10mg/kg DOX iv, (4) 50mg/kg ip FNP 30min before 10mg/kg iv DOX, (5) 100mg/kg ip FNP 30min before 10mg/kg iv DOX. A general health condition, body and liver weight, TBARS level and antioxidative enzyme activity, as well as pathohistological examination of the liver tissue were conducted on days 2 and 14 of the study. FNP, applied alone, did not alter any examinated parameters. Howev...
Studies on anti-tumor and antimetastatic activities of fullerenol in a mouse breast cancer model
2010
The purpose was to examine the anti-tumor and antimetastatic activities of fullerenol and their related mechanisms. Thirty EMT-6 tumor-bearing mice were injected intraperitoneally with 0.1 ml saline or 0.1 ml saline containing fullerenol C 60 (OH) 20 (0.08 and 0.4 mg/ml) daily for 16 days. Using tumor tissues, we investigated imbalances in the oxidative defense system and the expression of several angiogenesis factors. C 60 (OH) 20 exhibits anti-tumor and antimetastatic activities in EMT-6 breast cancer metastasis model. Treatment with C 60 (OH) 20 was found to modulate oxidative stress significantly. The expression of several angiogenesis factors was reduced in tumor tissues after treatment with fullerenol. Importantly, CD31 (also known as PECAM-1, platelet endothelial cell adhesion molecule) expression and vessel density were markedly reduced in tumors from fullerenol-treated mice compared with controls. Modulation of oxidative stress in tumor tissues, inhibition of the formation of angiogenesis factors, and subsequent reduction in tumor vessel density and the nutrient supply to tumor cells could be important mechanisms by which fullerenol aggregates inhibit tumor growth and suppress carcinoma metastasis in vivo.
Fullerenols as a New Therapeutic Approach in Nanomedicine
Volume 2013 (2013), Article ID 751913. , 2013
Recently, much attention has been paid to the bioactive properties of water-soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics. Anthracycline therapy, in spite of its effective antitumor activity, induces systemic oxidative stress, which interferes with the effectiveness of the treatment and results in serious side effects. Fullerenols may counteract the harmful effects of anthracyclines by scavenging free radicals and thereby improve the effects of chemotherapy. Additionally, due to the hollow spherical shape, fullerenols may be used as drug carriers. Moreover, because of the existence of the currently ineffective ways for neurodegenerative diseases treatment, alternative compounds, which could prevent the negative effects of oxidative stress in the brain, are still sought. In the search of alternative methods of treatment and diagnosis, today’s science is increasingly reaching for tools in the field of nanomedicine, for example, fullerenes and their water-soluble derivatives, which is addressed in the present paper.
Hepatoprotective effect of fullerenol/doxorubicin nanocomposite in acute treatment of healthy rats
Experimental and molecular pathology, 2018
In our recent studies we have designed fullerenol/doxorubicin nanocomposite (FNP/DOX) as the new drug nanocarrier. This research has demonstrated that this novel nanocomposite has had better implications on the liver tissue in vivo (Wistar rats treated intraperitoneally), than treatment based only on DOX. FNP/DOX has been characterised by DLS, TEM and AFM measurements which have shown that DOX loaded onto FNP did not influence fullerenol nanoparticle's size. FNP/DOX affected oxidative status in blood causing a significant decrease of catalase and SOD activity in comparison to DOX, implicating the reduction in oxidative stress. qRT-PCR results on the mRNA level of antioxidative enzymes (catalase and MnSOD) revealed that the effect of oxidative stress is significantly reduced by the treatment with FNP/DOX (p < .05). The ultrastructural analysis of the liver tissue has revealed that FNP/DOX nanocomposite generated considerably less damage in the liver tissue, than DOX applied at...
With the recent rapid development of nanoscience and nanotechnology, the interest in carbon nanomaterials has been gradually diverted into biological and medical fields. Water soluble fullerene (C 60) derivatives synthesized by attaching various polar functional groups to the fullerene cage are promising candidates for many biomedical applications [1]. Fullerene derivatives have the potential to scavenge reactive oxygen species (ROS) [2]. The chemical modification of fullerenes by adding the OH groups to their carbon surface yields a variety of polyhydroxylated structures C 60 (OH) x, also known as fullerenols or fullerols, exhibiting different degrees of solubility and antioxidant activity in the aqueous environment [3-5]. Fullerenol C 60 (OH) 24 nano-particles (FNP) , synthesized in alkaline media by complete substitution of bromine atoms from C 60 Br 24 [6], exerted
Mater Sci Forum, 2005
The aims of this paper were to investigate cell growth activity of fullerenol C 60 (OH) 24 , its modulating effect on antitumor drug-induced cytotoxicity, and genotoxic influence of fullerenol at nanomolar concentrations. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with fullerenol at concentrations from 0.9 to 3.9 µg/ml alone or simultaneously with antitumor drugs (doxorubicin, cisplatin, taxol, and tiazofurin; IC50 concentrations) for 2 hours. Growth inhibition was evaluated by colorimetric SRB assay after recovery period of 24, 48, and 96 hours. The genotoxic examination was performed using sister chromatid exchange test and micronucleus assay, at fullerenol concentration ranging from 1 to 5 µg/ml. The fullerenol alone mildly inhibits the growth of both cell lines. Simultaneous administration of fullerenol and antitumor drugs strongly suppressed antitumor drug-induced cytotoxicity. The rate of cytotoxicity inhibition depended on fullerenol concentration, type of antitumor drug and cell line. Protection against doxorubicin and cisplatin was more pronounced than against taxol and tiazofurin. Fullerenol was not found to be genotoxic to investigated cell lines.