BIOCHEMICAL MARKERS OF DAMAGE IN RATS EXPOSED BY ORAL GAVAGE TO SINGLE-WALLED CARBON NANOTUBES IN COMBINATION WITH ANTIOXIDANT PREPARATION “AEVIT”

Abstract

Introduction. The toxicity of carbon nanotubes (CNT), which are chemically inert particles, is thought to be connected with responses of aseptic inflammation and oxidative stress. This study was conducted to determine how far antioxidants may reduce CNT toxicity in laboratory animals. Material and methods. Male Wistar rats were administered by oral gavage with 0.05 or 0.5 mg/kg/day of Tuball© single-walled CNT in vegetable oil for 2 weeks, without a modifier or in combination with Aevit© (mixture of retinol and α-tocopherol given in doses 25,000 IU/kg/day and 25 mg/kg/day correspondingly). Control animals received oil or Aevit without CNT. 10 markers of oxidative stress and 12 clinical chemistry markers were determined in the rat blood samples. Results. Aevit didn’t influence the above biochemical markers, but combination “Aevit + CNT” increased the prooxidant action of CNT and arose biochemical signs of malabsorption, presumably as a result of retinol inhibitory action onto repair of intestinal epithelial cells, damaged by CNT. Discussion. The lack of tocopherol protective action, which usually removes prooxidant effects of high retinol concentrations, can be explained by superposition of two mechanisms: 1) two components of Aevit, in the presence of CNT, may be separated in space, since only retinol has isoprenoid side chain needed for the formation of donor-acceptor complexes with CNT surface; 2) the effects of retinol on cell reproduction, differentiation and wound healing is not related to its anti - or pro-oxidant properties but takes place at the level of target genes transcription after binding of retinoic acid with nuclear receptors RARs and RXRs. The data obtained allowed supposing the mechanism of lung cancer increases in ATBC and CARET trials was not prooxidant action of retinol and its precursor β-carotene, but regulatory inhibition of lung epitheliocytes reparation during its continued damage by cigarette smoke and asbestos fibers by retinoic acid. Conclusion. Aevit (and, probably, other retinoid-containing preparations) can’t be recommended to ensure the safety of humans and animals during oral CNT intake. The results obtained explanation needs both functional activities of retinol, which is simultaneously antioxidant and one of the nuclear regulators; this, in turn, leads to the new assumption about the mechanisms of unsuccessful outcomes in ATBC and CARET trials.