Biological & pharmaceutical bulletin
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Parkinson's disease (PD) is the second most common neurodegenerative disease. Although the etiology of PD is not completely understood, it is well-documented that oxidative stress and Ca(2+)-mediated cellular damage play important roles in the progression of PD. 2-[[(1,1-Dimethylethyl)oxidoimino]-methyl]-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has shown significant therapeutic effects in stroke models due to its multiple functions, including calcium overload blockade and free radical-scavenging. In this study, we investigated the neuroprotective and neurorescue effects of TBN on various in vitro and in vivo models of PD and explored its possible mechanisms of action. ⋯ In addition, TBN improved apomorphine-induced rotational behavior in the 6-OHDA-lesioned PD rats. TBN suppressed the MPP(+)-induced intracellular reactive oxygen species (ROS) in SH-SY5Y cells, increased the superoxide dismutase (SOD) activity and glutathione (GSH) concentration in the substantial nigra of MPTP-treated mice. These data indicate that TBN protects and rescues dopaminergic neurons from MPP(+) and MPTP/6-OHDA-induced damage by reducing ROS and increasing cellular antioxidative defense capability.
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Inflammatory pain and neuropathic pain are major health issues that represent considerable social and economic burden worldwide. In this study we investigated the potential of obtusifolin and gluco-obtusifolin, two anthraquinones found in the seeds of the widely used traditional Chinese medical botanical Cassia obtusifolia, to reduce neuropathic and inflammatory pain. The potential analgesic effects of obtusifolin and gluco-obtusifolin were evaluated by mice formalin test and complete Freund's adjuvant (CFA)-induced nociceptive behaviors in rats. ⋯ Furthermore, repeated administration of obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed mechanical allodynia induced by CFA, CCI, L5 SNL, diabetes, and oxaliplatin in a dose-dependent manner in rats. Levels of activated nuclear factor-kappa B (NF-κB) and proinflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α)) in lumbar spinal cord were elevated in rats following CFA treatment and CCI induction, and obtusifolin and gluco-obtusifolin significantly inhibited these effects. Our results demonstrate that obtusifolin and gluco-obtusifolin produce significant antinociceptive action in rodent behavioral models of inflammatory/neuropathic pain, and that this activity is associated with modulation of neuroinflammation in spinal cord.
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Observational Study
A retrospective study on the influence of nutritional status on pain management in cancer patients using the transdermal fentanyl patch.
It is unknown whether nutritional status influences pain intensity in cancer patients receiving a transdermal fentanyl patch (FP). This study aimed to determine whether nutritional status is associated with pain intensity and to evaluate the influence of changes in nutritional status on pain intensity in cancer patients receiving transdermal FP treatment. We included 92 patients receiving transdermal FP treatment for the first time with switching from oxycodone. ⋯ In 52 of 92 patients, who were evaluated using the NRS 2002 score and pain intensity on day 30 after FP application, the changes in NRS 2002 scores were significantly related to changes in pain intensities (odds ratio, 30.0; 95% confidence interval, 4.48-200.97; p=0.0005). These results suggest that an increase in the NRS 2002 score is a risk factor for an increase in pain intensity in cancer patients receiving FP treatment. Malnutrition may lead to poor pain management in cancer patients receiving FP treatment.
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We investigated the effects of epigenetic modifiers such as DNA methyltransferase (DNMT) or histone deacetylase (HDAC) inhibitors on the cytotoxicity induced by 3 anticancer drugs (5-fluorouracil (5-FU), irinotecan (CPT-11) or its active form SN38, and oxaliplatin (L-OHP)) in human colorectal cancer (CRC) cells. Cytotoxicity in 4 CRC cell lines (HT29, SW480, SW48 and HCT116) was examined by colorimetric assay after drug treatment for 72 h. The effects of drug combinations were analyzed by an isobologram method. ⋯ Thus, we examined whether the synergic effect of DAC is observed in other different CRC cell lines, HT29, SW48 and HCT116 cells. In all 4 CRC cell lines, the cytotoxicity of L-OHP was enhanced in a synergic manner by co-treatment with DAC. However, synergic effects of DAC with 5-FU or CPT-11 (SN-38) were not observed in 4 CRC cell lines.
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Pregabalin, (S)-3-isobutyl-γ-aminobutyric acid (GABA), is a widely used adjuvant therapy for patients with neuropathic pain, which is defined as chronic pain caused by lesions or diseases of the somatosensory nervous system. However, dizziness and somnolence (sleepiness) are common dose-limiting side effects, probably due to excessive sedative effects on higher centers of the central nervous system (CNS) which are involved in the anticonvulsant and analgesic actions of pregabalin. We speculated that transdermal delivery would minimize centrally mediated side effects. ⋯ Transdermally administered pregabalin increased the pain thresholds in response to mechanical stimuli in a partial sciatic nerve ligation model in rats and a spinal nerve ligation model in mice, and surprisingly also in normal animals. It is noteworthy that simple transdermal application of an aqueous solution of pregabalin is effective. This could be a useful treatment option to avoid or minimize the CNS-mediated side effects of orally administered pregabalin.