Protective effects of fullerenol against chronic doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

Abstract

Since the introduction of Doxorubicin (Dox) for the treatment of cancer in 1969, this compound has demonstrated high antitumor efficacy. Dox's use in chemotherapy has been limited largely due to its diverse toxicities, including cardiac, liver, renal, pulmonary, hematological and testicular toxicity. Various attempts have been made to reduce Dox-induced toxicity. These include dosage optimization, synthesis and use of analogues. Moreover, a number of agents have been investigated as protective agents during Dox therapy. Polyhydroxilated derivatives of fullerene, named fullerenols C60(OH)n, are being extensively studied due to their great potential as antioxidants. It is proposed that they might act as free radical scavengers in biological systems, in xenobiotics-induced oxidative stress as well as against radioactive irradiation. We have investigated the effects of fullerenol C60(OH)24 (Frl) at doses of 25, 50 and 100 mg kg-1 week (for a time-span of three weeks) on heart and liver tissue after Doxorubicin (Dox)-induced toxicity in rats with colorectal cancer. In the present study, in vivo Wistar male rat model was used to explore whether Frl could protect against Dox-induced (1.5 mg/kg/week for three weeks) chronic cardio- and hepatotoxicity and compared the effect with a well-known antioxidant, vitamin C (100 mg/kg/week for three weeks). Commercially available methods were used for blood and pathohystological analysis and for the measurement of enzyme activity (SOD, MDA, GSH, GSSH, GPx, GR, CAT, CK, LDH, ?-HBDH, AST, ALT) in serum and homogenate samples of heart and liver tissues. According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.