Oxidative damage induced by the fullerene C 60 on photosensitization in rat liver microsomes (original) (raw)
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Toxicology, 2000
Fullerenes have attracted considerable attention in recent years due to their unique chemical structure and potential applications. Hence it is of interest to study their biological effects. Using rat liver microsomes as model systems we have examined the ability of the most commonly used fullerene, C60 and its water-soluble derivative, C60(OH)18 to induce membrane damage on photosensitization. For photoexcitation, UV or tungsten lamps were used. Damage was assessed as lipid peroxidation products like conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), protein oxidation in the form of protein carbonyls, besides loss of membrane bound enzymes. Both fullerene derivatives induced significant oxidative damage. The alterations induced were both time- and concentration-dependent. Role of different reactive oxygen species (ROS) in the damage induced was examined by various scavengers of ROS and by deuteration of the buffer. The changes induced by C60 were predominantly due to 1O2 while that by C60(OH)18 was mainly due to radical species. Biological antioxidants such as glutathione, ascorbic acid and α-tocopherol were capable of inhibiting membrane damage induced by both the fullerenes. However, the damage induced by C60(OH)18 was more for both lipids and proteins than that showed by C60. C60 also showed enhancement in the formation of lipid peroxidation in sarcoma 180 ascites microsomes. In conclusion, our studies indicate that fullerene/its derivative can generate ROS on photoexcitation and can induce significant lipid peroxidation/protein oxidation in membranes and these phenomena can be prevented by endogenous/natural antioxidants.
Possible mechanisms of fullerene C 60 antioxidant action
Novel mechanism of antioxidant activity of buckminsterfullerene C 60 based on protons absorbing and mild uncoupling of mitochondrial respiration and phosphorylation was postulated. In the present study we confirm this hypothesis using computer modeling based on Density Functional Theory. Fullerene's geroprotective activity is sufficiently higher than those of the most powerful reactive oxygen species scavengers. We propose here that C 60 has an ability to acquire positive charge by absorbing inside several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and phosphorylation. This, in turn, leads to the decrease in ROS production.
Journal of Medicinal Chemistry, 1999
C 60 , vitamin E, and three C 60 derivatives (polar 1 and water-soluble C 3 /D 3 C 60 s) were examined for their antioxidant effects on prevention of lipid peroxidation induced by superoxide and hydroxyl radicals. The protection effect on lipid peroxidation was found to be in the sequence: C 60 g vitamin E > 1 > none, for liposoluble antioxidants, and C 3 C 60. D 3 C 60 > none, for watersoluble ones. Fluorescence quenching of PyCH 2 COOH (Py) pyrene) by both C 3-and D 3 C 60 s shows that the Stern-Volmer constant, K SV , is about the same for both quenchers in aqueous solution. Upon addition of liposomes, the fluorescence quenching becomes more efficient: 5-fold higher in K SV for C 3 C 60 than for D 3 C 60. When Py(CH 2) n COOH (n) 1, 3, 5, 9, or 15) was incorporated in lipid membranes, the K SV s all were small and nearly equal for D 3 C 60 but were quite large and different for C 3 C 60 with the sequence: n) 1 < 3 < 5 < 9 < 15. The better protection effect of C 3 C 60 on lipid peroxidation than that of D 3 C 60 is attributed to its stronger interaction with membranes. Overall, the antioxidation abilities of the compounds examined were rationalized in terms of the number of reactive sites, the location of antioxidant in lipid membranes, and the strength of interactions between antioxidants and membranes.
Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C 60
Biomaterials, 2008
Fullerene (C 60 ), a third carbon allotrope, is a classical engineered material with the potential application in biomedicine. One of the biologically most relevant features of C 60 is the ability to quench various free radicals, behaving as a ''free radical sponge''. Conversely, photosensitization of C 60 leads to its transition to a long-lived triplet excited state and the subsequent energy or electron transfer to molecular oxygen, yielding highly reactive singlet oxygen ( 1 O 2 ) or superoxide anion (O 2 À ), respectively. These reactive oxygen species (ROS) react with a wide range of biological targets and are known to be involved in both cellular signaling and cell damage. Therefore, the dual property of fullerenes to either quench or generate cell-damaging ROS could be potentially exploited for their development as cytoprotective or cytotoxic anticancer/antimicrobial agents. However, the attempts to that effect have been hampered by the extremely low water solubility of C 60 , and by the fact that solubilization procedures profoundly influence the ROS-generating/quenching properties of C 60 , either through chemical modification or through formation of complex nanoscale particles with different photophysical properties. We here analyze the mechanisms and biological consequences of ROS generation/quenching by C 60 , focusing on the influence that different physico-chemical alterations exert on its ROS-related biological behavior.
Zanjan University of Medical Sciences, 2019
Article Info ABSTRACT 10.30699/jambs.27.124.8 Background & Objective: The potent antioxidant property of fullerene C60 nanoparticles and their derivatives has been demonstrated in a wide range of in vitro and in vivo studies. Hence, we examined the effects of fullerene C60 on the oxidative stress parameters in brain and liver of the rats in normal situation. Materials & Methods: The study was performed in two groups of Wistar rats (each group, n = 6); normal and fullerene-treated normal animals. Treated rats received fullerene via oral gavage at dose of 1 mg/kg/day for 60 days. At termination of the study, the oxidative stress parameters were determined in brain and liver tissues, including the contents of glutathione (GSH) and malondialdehyde (MDA), and the activities of catalase (CAT) and superoxide dismutase (SOD). The t-test was used to analyze the data between two groups. Results: Fullerene C60 treatment did not change blood glucose level in treated rats compared to untreated rats. Fullerene C60 significantly increased the value of CAT activity by 66% and MDA levels by 68%, while decreased SOD activity by 33% at liver of treated rats compared to untreated animals (P<0.05). Fullerene administration increased significantly only CAT activity of brain in the treated rats (0.34±0.10 U/mg protein) compared to untreated animals (0.12±0.03 U/mg protein), (P<0.05). Conclusion: Our findings indicated that oral administration of fullerene C60 nanoparticles differently changed the oxidative stress parameters in liver and brain in normal condition. It is suggested that these effects be considered for the application of these nanoparticles in various therapeutic purposes.
Journal of Advances in Medical and Biomedical Research
Background & Objective: The potent antioxidant property of fullerene C60 nanoparticles and their derivatives has been demonstrated in a wide range of in vitro and in vivo studies. Hence, we examined the effects of fullerene C60 on the oxidative stress parameters in brain and liver of the rats in normal situation. Materials & Methods: The study was performed in two groups of Wistar rats (each group, n = 6); normal and fullerene-treated normal animals. Treated rats received fullerene via oral gavage at dose of 1 mg/kg/day for 60 days. At termination of the study, the oxidative stress parameters were determined in brain and liver tissues, including the contents of glutathione (GSH) and malondialdehyde (MDA), and the activities of catalase (CAT) and superoxide dismutase (SOD). The t-test was used to analyze the data between two groups. Results: Fullerene C60 treatment did not change blood glucose level in treated rats compared to untreated rats. Fullerene C60 significantly increased the value of CAT activity by 66% and MDA levels by 68%, while decreased SOD activity by 33% at liver of treated rats compared to untreated animals (P<0.05). Fullerene administration increased significantly only CAT activity of brain in the treated rats (0.34±0.10 U/mg protein) compared to untreated animals (0.12±0.03 U/mg protein), (P<0.05). Conclusion: Our findings indicated that oral administration of fullerene C60 nanoparticles differently changed the oxidative stress parameters in liver and brain in normal condition. It is suggested that these effects be considered for the application of these nanoparticles in various therapeutic purposes.
Photodiagnosis and Photodynamic Therapy, 2013
The photodynamic mechanism of action induced by N,N-dimethyl-2-(4-N,N,Ntrimethylaminophenyl)fulleropyrrolidinium iodide (DTC 60 2+) was investigated on Candida albicans and Escherichia coli cells. First, photogeneration of superoxide anion radical by DTC 60 2+ in the presence of NADH was detected using nitro blue tetrazolium method in reverse micelles. In C. albicans suspensions, 10 M DTC 60 2+ was an effective photosensitizer, producing a ∼5 log decrease of cell survival when the cultures were irradiated for 30 min with visible light. Also, C. albicans cells growth was not detected in the presence of 10 M DTC 60 2+ and irradiation. Photodynamic mechanism investigations were compared in both C. albicans and E. coli cells. Studies under anoxic conditions indicated that oxygen was required for the photodynamic inactivation of these microorganisms. The photocytotoxicity induced by DTC 60 2+ was similar in D 2 O than in water cell suspensions. Furthermore, photoinactivation of microbial cells was negligible in the presence of azide ion, while the addition of mannitol produced a photoprotective effect on the cellular survival. These results indicate that DTC 60 2+ has potential as agent to the photodynamic inactivation of microbial cells. Also, the photocytotoxicity activity induced by this cationic fullerene derivative can involve the intermediacy of both superoxide anion radical and singlet molecular oxygen.
Environmental Toxicology and Chemistry, 2012
Studies concerning the impact of nanomaterials, especially fullerene (C 60 ), in fresh water environments and their effects on the physiology of aquatic organisms are still scarce and conflicting. We aimed to assess in vitro effects of fullerene in brain and gill homogenates of carp Cyprinus carpio, evaluating redox parameters. A fullerene suspension was prepared by continued stirring under fluorescent light during two months. The suspension concentration was measured by total carbon content and ultraviolet-visible spectroscopy nephelometry. Characterization of C 60 aggregates was performed with an enhanced dark-field microscopy system and transmission electronic microscopy. Organ homogenates were exposed during 1, 2, and 4 h under fluorescent light. Redox parameters evaluated were reduced glutathione and oxidized glutathione, cysteine and cystine, total antioxidant capacity; activity of the antioxidant enzymes glutathione S-transferase and glutathione reductase (GR), and lipid peroxidation (TBARS assay). Fullerene induced a significant increase ( p < 0.05) in lipid peroxidation after 2 h in both organs and reduced GR activity after 1 h (gills) and 4 h (brain) and antioxidant capacity after 4 h (brain). Levels of oxidized glutathione increased in the brain at 1 h and decreased at 2 h as well. Given these results, it can be concluded that C 60 can induce redox disruption via thiol/disulfide pathway, leading to oxidative damage (higher TBARS values) and loss of antioxidant competence. Environ. Toxicol. Chem. 2012;31:961-967. # 2012 SETAC
Archives of Toxicology, 2012
The fullerene C 60 , due to the physicochemical properties of its spherical cage-like molecule build exclusively from carbon atoms, is able to both scavenge and generate reactive oxygen species. While this unique dual property could be exploited in biomedicine, the low water solubility of C 60 hampers the investigation of its behavior in biological systems. The C 60 can be brought into water by solvent extraction, by complexation with surfactants/ polymers, or by long-term stirring, yielding pristine (unmodified) fullerene suspensions. On the other hand, a modification of the C 60 core by the attachment of various functional groups results in the formation of water-soluble fullerene derivatives. Assessment of toxicity associated with C 60 preparations is of pivotal importance for their biomedical application as cytoprotective (antioxidant), cytotoxic (anticancer), or drug delivery agents. Moreover, the widespread industrial utilization of fullerenes may also have implications for human health. However, the alterations in physicochemical properties imposed by the utilization of different methods for C 60 solubilization profoundly influence toxicological effects of fullerene preparations, thus making the analysis of their potential therapeutic and environmental toxicity difficult. This review provides a comprehensive evaluation of the in vitro and in vivo toxicity of fullerenes, focusing on the comparison between pristine and derivatized C 60 preparations and the mechanisms of their toxicity to mammalian cells and tissues.
Journal of applied toxicology : JAT, 2015
DNA damage and cytotoxicity induced by a hydroxylated fullerene [C60 (OH)24 ], which is a spherical nanomaterial and/or a water-soluble fullerene derivative, and their protection by sulfhydryl compounds were studied in freshly isolated rat hepatocytes. The exposure of hepatocytes to C60 (OH)24 at a concentration of 50 μM caused time (0 to 3 h)-dependent cell death accompanied by the formation of cell surface blebs, the loss of cellular levels of ATP and reduced glutathione, accumulation of glutathione disulfide, and induction of DNA fragmentation assayed using alkali single-cell agarose-gel electrophoresis. C60 (OH)24 -induced cytotoxicity was effectively prevented by pretreatment with sulfhydryl compounds. N-acetyl-L-cysteine (NAC), L-cysteine and L-methionine, at a concentration of 2.5 mM, ameliorated cell death, accompanied by a decrease in cellular ATP levels, formation of cell surface blebs, induction of reactive oxygen species (ROS) and loss of mitochondrial membrane potential...