Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications

• Published in: Toxicology (Amsterdam) Vol. 155; no. 1; pp. 55 - 61
• Main Authors: Kamat, J.P., Devasagayam, T.P.A., Priyadarsini, K.I., Mohan, H.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 30.11.2000
• Subjects: Animals; Antioxidants; Ascitic Fluid - drug therapy; Ascitic Fluid - metabolism; Ascitic Fluid - radiotherapy; Ascorbic Acid - pharmacology; Carbon - pharmacology; Dose-Response Relationship, Drug; Drug Antagonism; Fullerenes; Glutathione - pharmacology; Intracellular Membranes - drug effects; Intracellular Membranes - physiology; Intracellular Membranes - radiation effects; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipid Peroxidation - radiation effects; Microsome; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Microsomes, Liver - radiation effects; Models, Animal; Photosensitization; Photosensitizing Agents - pharmacology; Rats; Reactive Oxygen Species - physiology; Sarcoma 180 - metabolism; Vitamin E - pharmacology; Antioxidants; Photosensitization; Fullerenes; Lipid peroxidation; Microsome
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(00)00277-8

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, C 60 and its water-soluble derivative, C 60(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 C 60 were predominantly due to 1O 2 while that by C 60(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 C 60(OH) 18 was more for both lipids and proteins than that showed by C 60. C 60 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.