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Water soluble fullerene (C60) derivative fullerenol C60(OH)24 nano-particles (FNP) are a promising candidate for many biomedical applications due to, besides other properties, strong free-radical scavenging and antioxidative potential. Using the carrageenan-induced rat footpad oedema test, the anti-inflammatory effect of FNP have been estimated in comparison with those of amifostine (AMI) and indomethacin (IND). FNP and IND, dissolved in dimethylsulfoxide, and AMI, dissolved in saline, were intraperitoneally injected to rats in a dose range 12.5 - 75 mg/kg, 3 - 10 mg/kg, and 50 - 300 mg/kg, respectively. The control groups were given corresponding vehicles. The drugs or vehicles were given 30 min before carrageenan injection. Footpad swelling was measured 3 hours after carrageenan application. Calculation of a per cent of inhibition derived through comparison with the control groups was done. Histopathological examination of the inflamed foot skin biopsies was also performed. FNP dose-dependently and significantly reduced the extent of footpad oedema, comparable to that of IND and significantly better than AMI; their ED50 values (in μmol/kg) were: 35.36, 32.12 and 871.0, respectively. Histopathological examination confirmed these results. The largest therapeutic index of FNP suggests their safety for potential use in humans. Our results support the hypothesis that FNP produce a strong acute anti-inflammatory activity.
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... Further, progressive loss of renal function was tightly associated with increased levels of creatinine, uric acid, and blood urea nitrogen [11,28]. It is considered that the successful prevention or treatment of these DOX-induced harmful effects depends on antioxidative potential of different cytoprotective agents and their ability to react with highly reactive oxygen species (ROS) [12,13,26,[28][29][30][31][32]. ...
... Moreover, in our study, in AMI-treated group, both in the liver and kidney of the experimental animals, most of the blood vessels were just slightly dilated without prominent alterations in their basal membranes, and were surrounded by small groups or by individual PMNCs. In our previous work, we actually showed that AMI in a range of doses, from 100 to 300 mg/kg body weight, had potent anti-inflammatory activity in a model of acute inflammation in rats [29]. This mechanism of action might additionally offer protection against DOX-induced acute [12,33], and especially chronic [69] cardiotoxicity in rats. ...
... This mechanism of action might additionally offer protection against DOX-induced acute [12,33], and especially chronic [69] cardiotoxicity in rats. It was probably a consequence of inhibition of PMNCs infiltration, as well as main pro-inflammatory mediator production, including free radicals [12,29,33,36,59,70,71]. Therefore, we hypothesize that protective effects of AMI against hepatic and renal alterations caused by DOX are also based on its potent antioxidative and anti-inflammatory effects. ...
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... • a mean lethal dose (LD 50 ) [178,179], • pharmacological-toxicological profile (i.e., absorption, distribution, metabolism, and excretion (ADME)) [180][181][182][183], as well as • pathohistological alterations in tissues in which they primarily accumulate [176,180]. In these studies, the acute toxicity of FNPs was directly dependent on the dose administered, the exposure conditions, and the duration of exposure. ...
... The relatively lower toxicity has been confirmed in our previous in vivo studies when FNPs were applied in an increasing-dose regimen. The calculated medial lethal dose (LD 50 ) [178,179], however, has reached similar values, as can be seen in Figure 6a,b. Nanomaterials 2020, 10, 1508 19 of 30 ...
... In addition, due to the possible different routes of exposure, assessment of acute FNP toxicity is the first step in considering their general toxic effects [17]. Namely, FNP toxicity studies performed mainly in mice and rats [177] were based on the determination of:  a mean lethal dose (LD50) [178,179],  pharmacological-toxicological profile (i.e., absorption, distribution, metabolism, and excretion (ADME)) [180][181][182][183], as well as  pathohistological alterations in tissues in which they primarily accumulate [176,180]. In these studies, the acute toxicity of FNPs was directly dependent on the dose administered, the exposure conditions, and the duration of exposure. ...
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Chapter
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... For example, Chedid et al. demonstrated the ability of vasoactive intestinal peptide (VIP) to reduce cellular ROS production in vitro and ameliorate footpad edema in vivo when administered 1 day and 1 h prior to carrageenan injection. 73 Similarly, antioxidant fullerenol nanoparticles 74 and Ficus exasperata bark extract 75 significantly reduced edema as a prophylactic treatment. These results support systemic antioxidant treatment for aggressively inflammatory conditions. ...
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... Additionally, Injac et al. confirmed that polyhydroxylated fullerene derivatives could be as potential antioxidant agents in biological systems (Injac et al., 2013). Moreover, it has been reported that fullerene nanoparticles have anti-inflammatory activity (Dragojevic-Simic et al., 2011). According to mentioned studies, oxygen free radicals (ROS) play a crucial role in pathogenesis of reperfusion injury after ischemic stroke. ...
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... The carrageenan-induced rat footpad edema test performed by Dragojevic Simic et al. showed that when all the formulations were intraperitoneally injected to rats in different doses, the fullerol nanoparticles significantly reduced the extent of footpad edema in a dosedependent manner as compared with amifostine and indomethacin. The results were confirmed by the following histopathological examination (Dragojevic Simic et al., 2011). ...
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