3 research outputs found
Esculetin (dihydroxycoumarin) inhibits the production of matrix metalloproteinases in cartilage explants, and oral administration of its prodrug, CPA-926, suppresses cartilage destruction in rabbit experimental osteoarthritis
Objective. To investigate the in vitro effects of 6,7-dihydroxycoumarin (esculetin) on the production of matrix metalloproteinases (MMP) in rabbit articular cartilage, and the in vivo effects of orally administered CPA-926, a prodrug of esculetin, on cartilage destruction in rabbit experimental osteoarthritis (OA). Methods. In vitro studies were performed using rabbit articular cartilage explants. Esculetin 10-100 μM was added to cartilage explants in the presence or absence of interleukin 1α (IL-1α). Effects of esculetin on cartilage metabolism were assessed. Proteoglycan release into medium was determined by dye precipitation with 1,9-dimethylmethylene blue, synthesis of proMMP-1 (interstitial procollagenase) and proMMP-3 (prostromelysin 1) by Western blotting, and collagen degradation activity using FITC labeled collagen. In vivo experimental OA was induced in the knee joints of 15 Japanese adult white rabbits by partial lateral meniscectomy. Ten rabbits were orally administered 200 or 400 mg/kg/day of CPA-926 from the day of surgery for 14 days. The size of the macroscopic erosive area on the femoral condyle and tibial plateau was measured, and cartilage destruction was histologically evaluated. Collagenolytic activities in synovial fluid were measured using FITC labeled collagen as a substrate. Results. In vitro, esculetin inhibited the IL-1α induced release of proteoglycan into the medium in a dose dependent manner. The collagenolytic activities in cartilage explant medium induced by IL-1α were also suppressed with the addition of 33-100 μM esculetin (p = 0.0209 at 33 and 100 μM, p = 0.0202 at 66 μM). Western blotting of cartilage explant medium showed a decrease in the levels of proMMP-1 and proMMP-3 in the medium by treatment with esculetin. In vivo: At 14 days after surgery, the femoral condyle and tibial plateau in the control group showed macroscopic erosions of cartilage. Compared with the control group, the rabbits treated with CPA-926 at the dose of 400 mg/kg exhibited reduction of the size of the erosive area on the tibial plateau (p = 0.009). Histological evaluation indicated protection against the development of destructive changes in the tibial plateau cartilage at a dose of 200 mg/kg (p = 0.0442) and 400 mg/kg (p = 0.0446) of CPA-926. Conclusion. These results indicate that esculetin inhibits matrix degradation in rabbit joint cartilage explants through the suppression of MMP synthesis, secretion, or activity. Prophylactic administration of its prodrug, CPA-926, appears to provide some protection against cartilage destruction in a short term rabbit experimental OA model
The relationship between taste threshold change and serum zinc level in cancer patients treated with anticancer drugs <Original Articles>
化学療法の有害事象のうち味覚障害は発生頻度の高い有害事象である.味覚と血清亜鉛値との関連については以前から指摘されているが,抗がん剤投与後の味覚変化に血清亜鉛値が影響していることを示した報告は少ない.本研究の目的は,抗がん剤投与後のがん患者の味覚閾値と血清亜鉛値を測定し,両者の関連性を検証することである.60名のがん患者の抗がん剤投与前,抗がん剤投与後3日と投与後6日に味覚と血清亜鉛値,血清銅値を測定した.
抗がん剤投与後の味覚の変化は,塩味で時間経過による有意差を認めた(p<0.01).血清亜鉛値でも時間経過による有意差を認めた(p<0.01).味覚と血清亜鉛値との関係では,抗がん剤投与後3日において,血清亜鉛値と塩味の感度に負の相関を認め(r =- 0.402,p<0.01),血清亜鉛値が低い時,塩味の感度が鈍麻したことが示された.一方,血清銅値と味覚感度には相関を認めなかった.抗がん剤投与後の味覚感度,特に塩味の鈍麻については血清亜鉛値との関連が示された.Taste disorder is one of the most frequent side effects of chemotherapy. A relationship between serum zinc level and taste sensitivity has been pointed out in previous reports, but there have only been a few reports showing the effect of serum zinc level on taste sensitivity after anticancer drug administration. The purpose of this study was to examine the serum zinc levels and taste thresholds of cancer patients treated with anticancer drugs and to determine whether they are related.
Taste thresholds and levels of serum trace elements (zinc and copper) were measured in 60 cancer patients before administration of anticancer drugs and on the three and six days after administration.
There were significant differences in the salt threshold with elapse of time after chemotherapy (p<0.01). There were also significant differences in the serum zinc level with elapse of time after chemotherapy (p<0.01). There was a significant relationship between low salt sensitivity and change in serum zinc value (r = -0.402, p<0.01). Although there was no significant relationship between serum copper value and taste sensitivity, there was a relationship between salt sensitivity and serum zinc value