Fullerenes are a type of carbon molecules first discovered in the mid-1980s. The most well-known of these is the buckyball, which is a closed spherical molecule, shaped like a soccer ball. Many studies are presently in progress to search for pharmaceutical products that can capitalize on the excellent bioactivity of fullerenes and their derivatives. Thus far, different fullerene properties have been put to use, such as its ability to eliminate radicals as well as its particular molecular structure. Studies have found it to be efficient in suppression of metastases, treatment of cerebral conditions such as Alzheimer's and Parkinson's diseases, type-C hepatitis therapy, and HIV treatment. A polyhydroxilated derivative of fullerene, named fullerenols C60(OH)n, is being extensively studied due to its great potential as an antioxidant. It is proposed that fullerenols may act as free radical scavengers in biological systems, in xenobiotics, as well as radioactive irradiation-induced oxidative stress. It has demonstrated protective effects against cytotoxicity of doxorubicin (Dox) in animal models, especially by fullerenol C60(OH)24.
Different rat models with chemically induced cancer were used to investigate a potential protective role of fullerenol against cardio-, hepato-, nephro- and pulmotoxicity induced by Dox. According to preliminary studies on healthy adult Wistar rats, our research group confirmed that 100 mg/kg (i.p.) of fullerenol administered 30 min before Dox has a protective influence on heart and liver tissue. Therefore, that dose was chosen as effective against acute and chronic Dox-induced toxicity in further examinations. An in vivo – in vitro study was examined to confirm the potential protective role of fullerenol C60(OH)24 on Dox-induced liver toxicity. The in vivo results (Sprague-Dawley rats) showed that treatment with Dox alone caused significant changes in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alpha-hydroxybutyrate dehydrogenase (α-HBDH), as well as in levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) in the liver tissue. These effects were drastically reduced for all investigated parameters by pretreatment with fullerenol, although not for the MDA and GSH level. On the other hand, the human hepatocellular carcinoma (HepG2) cell line was continuously treated with fullerenol for 12, 24, 48 and 96 h, at concentrations of 10 and 44 μg/mL. With the aim of evaluating the modulating activity of fullerenol on Dox-induced hepatotoxicity, the cell line was concurrently treated with Dox (1 μM; 5 μM) and fullerenol (10 μg/mL; 44 μg/mL) in different combinations. When the cells are treated with 5 μM Dox along with the fullerenol, a significant development of cell capability during the entire timeline can be seen. It was concluded that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high, the cytotoxic effects of fullerenol are overcome bits protective role as a strong antioxidant compound. Damage to the heart muscle after Dox administration was also confirmed by changes in the ultstructural pathology results and SOD, MDA, CAT, GSSG (oxidized GSH), GR, and TAS levels, well as potential cardioprotective influence of fullerenol as a pretreatment agent for Dox therapy the acute phase. Fullerenol itself, in a dose of 100 mg/kg, did not affect heart injury in rats witbreast cancer. The presented results suggested that fullerenol might be a potential cardioprotector Dox-treated individuals.Effects of fullerenol C60(OH)24 at three different doses (25, 50, and 100 mg/kg/week) on heart anliver tissue after Dox-induced toxicity in rats with colorectal cancer were investigated durig a timspan of three weeks. An in vivo Wistar male rat model was used to explore whether fullerenocould protect against Dox-induced (1.5 mg/kg/week for three weeks) chronic cardio- andhepatotoxicity, and the effect was compared with a well-known antioxidant, vitamin C (10mg/kg/week for three weeks). According to macroscopic, microscopic, hematological, biochemicaphysiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examinedoses, fullerenol exhibits a protective influence on the heart and liver tissue against chronic toxiciinduced by Dox. The key benefit of fullerenol, in contrast to other known antioxidants, is its dual function as radprotector and organo-protector (heart, liver, kidney, and lung) during the anticancer therapy (radiand chemo-). However, there is a need to carry out further studies, including an acute and chroninvestigation in small pigs, and then after human trials.
|
