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Fullerene C60 Protects Against Intestinal Injury from Deoxynivalenol Toxicity by Improving Antioxidant Capacity.

ABSTRACT: Oxidative stress is involved in a wide variety of pathologies, and fullerene has been shown to have an antioxidant ability. Mycotoxins exert toxic effects through induction of excessive reactive oxygen species (ROS). Here, we evaluated water-soluble fullerene C60 for its anti-mycotoxin and antioxidant effects in vitro and in vivo. Intestinal epithelial cells were cultured with fullerene during deoxynivalenol (DON) exposure. The results revealed that fullerene C60 significantly promoted cell viability, decreased apoptosis and necrotic cell number, and significantly reduced intracellular ROS levels during DON exposure (p < 0.05). To investigate the role of fullerene in antioxidant capacity in vivo further, 40 three-week-old male C57BL/6 mice were randomly divided into four groups. There were no significant differences between the control and fullerene groups (p > 0.05). In mice exposed to DON, supplementation with fullerene C60 significantly improved growth performance, and enhanced the total antioxidant status and the activities of SOD and GPX in the intestine and liver (p < 0.05). In addition, fullerene C60 supplementation improved intestinal morphology, as indicated by a higher villus height and tight junction protein expression (p < 0.05). Furthermore, fullerene supplementation decreased serum concentrations of inflammatory cytokine and lipopolysaccharide (LPS; a penetrability marker) compared to the DON-challenged group (p < 0.05). The current study suggests that fullerene C60 improves intestinal antioxidant status against DON-induced oxidative stress in vitro and in vivo.

SUBMITTER: Liao S

PROVIDER: S-EPMC8229202 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: C60 fullerene has received great attention as a candidate for biomedical applications. Due to unique structure and properties, C60 fullerene nanoparticles are supposed to be useful in drug delivery, photodynamic therapy (PDT) of cancer, and reversion of tumor cells' multidrug resistance. The aim of this study was to elucidate the possible molecular mechanisms involved in photoexcited C60 fullerene-dependent enhancement of cisplatin toxicity against leukemic cells resistant to cisplatin. Methods: Stable homogeneous pristine C60 fullerene aqueous colloid solution (10-4 ?, purity 99.5%) was used in the study. The photoactivation of C60 fullerene accumulated by L1210R cells was done by irradiation in microplates with light-emitting diode lamp (420-700 nm light, 100 mW·cm-2). Cells were further incubated with the addition of Cis-Pt to a final concentration of 1 ?g/mL. Activation of p38 MAPK was visualized by Western blot analysis. Flow cytometry was used for the estimation of cells distribution on cell cycle. Mitochondrial membrane potential (??m) was estimated with the use of fluorescent potential-sensitive probe TMRE (Tetramethylrhodamine Ethyl Ester). Results: Cis-Pt applied alone at 1 ?g/mL concentration failed to affect mitochondrial membrane potential in L1210R cells or cell cycle distribution as compared with untreated cells. Activation of ROS-sensitive proapoptotic p38 kinase and enhanced content of cells in subG1 phase were detected after irradiation of L1210R cells treated with 10-5M C60 fullerene. Combined treatment with photoexcited C60 fullerene and Cis-Pt was followed by the dissipation of ??m at early-term period, blockage of cell transition into S phase, and considerable accumulation of cells in proapoptotic subG1 phase at prolonged incubation. Conclusion: The effect of the synergic cytotoxic activity of both agents allowed to suppose that photoexcited C60 fullerene promoted Cis-Pt accumulation in leukemic cells resistant to Cis-Pt. The data obtained could be useful for the development of new approaches to overcome drug-resistance of leukemic cells.

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Fullerene C60 Protects Against Intestinal Injury from Deoxynivalenol Toxicity by Improving Antioxidant Capacity.

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