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

Fullerenes have attracted considerable attention in recent years due to the ir unique chemical structure and potential applications. Hence it is of int erest to study their biological effects. Using rat liver microsomes as mode l 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 dam age on photosensitization. For photoexcitation, UV or tungsten lamps were u sed. Damage was assessed as lipid peroxidation products like conjugated die nes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBAR S), protein oxidation in the form of protein carbonyls, besides loss of mem brane bound enzymes. Both fullerene derivatives induced significant oxidati ve damage. The alterations induced were both time- and concentration-depend ent. 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 O-1(2) while that by C-60(OH)(18) was mainly due to radical species. Biological antioxidants su ch as glutathione, ascorbic acid and a-tocopherol were capable of inhibitin g membrane damage induced by both the fullerenes. However, the damage induc ed by C-60(OH)(18) was more for both lipids and proteins than that showed b y C-60. C-60 also showed enhancement in the formation of lipid peroxidation in sarcoma 180 ascites microsomes. In conclusion, our studies indicate tha t fullerene/its derivative can generate ROS on photoexcitation and can indu ce significant lipid peroxidation/protein oxidation in membranes and these phenomena can be prevented by endogenous/natural antioxidants. (C) 2000 Els evier Science Ireland Ltd. All rights reserved.