Pharmacol Rep
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To investigate the cytotoxicity of FM-Nov17 against chronic myeloid leukemia (CML) cells, we explored its underlying mechanisms mediating the induction of DNA damage and apoptotic cell death by reactive oxygen species (ROS). ⋯ FM-Nov17-induces DNA damage and mitochondria-dependent cellular apoptosis in CML cells. The process is mediated by the generation of ROS.
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Prolonged morphine treatment leads to antinociceptive tolerance. Suppression of spinal astrocytes or d-amino acid oxidase (DAAO), an astroglial enzyme catalyzing oxidation of d-amino acids, has reversed morphine antinociceptive tolerance. Since the astrocyte-DAAO pathway generates hydrogen peroxide, an agonist of the TRPA1 channel expressed spinally on nociceptive nerve terminals and astrocytes, we tested a hypothesis that the spinal TRPA1 contributes to antinociceptive tolerance to prolonged spinal morphine treatment. ⋯ Antinociceptive morphine tolerance and up-regulation of spinal DAAO were attenuated in morphine-treated animals by blocking the spinal TRPA1. This finding suggests that spinal TRPA1 may contribute, at least partly, to facilitation of morphine antinociceptive tolerance through mechanisms that possibly involve TRPA1-mediated up-regulation of the astroglial DAAO, a generator of hydrogen peroxide, a pronociceptive compound acting also on TRPA1.
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The purpose of this study was to determine the role of spinal 5-HT2A, 5-HT2B and 5-HT2C receptors in the development and maintenance of formalin-induced long-lasting secondary allodynia and hyperalgesia in rats, as well as their expression in the dorsal root ganglia (DRG) during this process. ⋯ Data suggest that spinal 5-HT2A/2B/2C receptors have pronociceptive effects and participate in the development and maintenance of formalin-induced long-lasting hypersensitivity. These receptors are expressed in DRG and their expression is modulated by formalin.