Anti-inflammatory and Anti-apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage

Background: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. Aims: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition. Study Design: Animal experimentation. Methods: Twenty-six Wistar rats were randomized into four groups: control (CTRL), radiation (RT), VA plus radiation (VA+RT), and DX plus radiation (DX+RT).Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and matrix metalloproteinases (MMP-2 and MMP 9) were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: VA decreased the levels of TNF-α and IL-1β proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis. Conclusion: Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in early radiation and these effects are independent from MMP inhibition

Anti-inflammatory and Anti-apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage

Background: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. Aims: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition. Study Design: Animal experimentation. Methods: Twenty-six Wistar rats were randomized into four groups: control (CTRL), radiation (RT), VA plus radiation (VA+RT), and DX plus radiation (DX+RT).Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and matrix metalloproteinases (MMP-2 and MMP 9) were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: VA decreased the levels of TNF-α and IL-1β proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis. Conclusion: Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in early radiation and these effects are independent from MMP inhibition

Ritmik cimmastikçilerde sıçrama yükseklikleri, izokinetik kuvvet ve EMG profillerinin karşılaştırılması

The aim of the present study was to investigate the relationships between EMG records and vertical jumping scores and isokinetic strength on the preferred legs of the rhythmic gymnasts. Eleven elite rhythmic female gymnasts volunteered to participate to the study. The mean age, body weight and body fat percentage of the subjects were 11.6;plusmn;1.8 years, 30.3;plusmn;5.5 kg and 7.9;plusmn;2.7 % (mean;plusmn;SD), respectively. The subjects performed triple maximal vertical jumps on their preferred (right) leg and double legs on ;quot;Newtest;quot; jumping platform. Surface EMG data of leg muscles (quadriceps femoris and biceps femoris) were recorded during the jumps (Biopac MP30). On a separate day, subjects performed flexio and extension muscle contractions at three randomly selected contraction velocities (60, 180 and 300 ;deg;/s) (Cybex II). The median frequencies (mf) and power spectrum analyses (rms) were done from EMG records. Mean jumping heights of one and double-leg jumps were 16.3+2.3 and29.6;plusmn;2.8 cm, respectively. Right leg flexion peak torques at 60, 180 and 300 ;deg;/s were 46.3;plusmn;9.9, 38.3;plusmn;9.4 and 26.7;plusmn;7.5 Nm; and, extension peak torques at 60, 180 and 300 ;deg;/s were 78.2+12.7, 53.3+12.4 and 37.4;plusmn;9.2 Nm, respectively. A statistically significant correlation was found between jumping heights and right biceps femoris EMG rms values at both one and double-leg jumps (p;lt;0.05). No significant relations were observed between isokinetic force values and EMG data. There were small numbers of studies involved with rhythmic gymnasts and/or that age group. The results of this study supported the earlier findings that revealed a relation between vertical jumping height and EMG power spectrum. Contrary to the studies suggested a correlation between contraction force and EMG data of quadriceps femoris muscle, no correlation was found among EMG data, force production of quadriceps femoris muscle and vertical jumping height in the present study. This result may be due to the difference of the properties of the subjects comparing to the other studies.Bu çalışmada ritmik cimnastikçilerin tek ve çift bacak dikey sıçrama sırasında EMG verileri ile dikey sıçrama yükseklikleri ve izokinetik kuvvet ölçümleri arasındaki ilişki araştırılmıştır. On bir elit ritmik cimnastikçi gönüllü olarak çalışmaya katılmıştır. Deneklerin yaş, vücut ağırlığı ve vücut yağ yüzdeleri sırasıyla (ortalama±SS) 11.6±1.8yıl, 30.3±5.5 kg, 7.9±2.7 dir. Denekler Newtest platformu üzerinde üçer kez çift ve tek bacak üzerinde sıçrama yapmışlardır. Sıçrama sırasında sağ bacak quadriseps ve biseps femoris kaslarından yüzeyel elektrodlar ile EMG kayıtları alınmış (Biopac MP30), farklı bir günde ise 60, 180 ve 300 °/sn'de fleksiyon ve ekstansiyon izokinetik kuvvet ölçümleri yapılmıştır (Cybexll). EMG kayıtlarından medyan frekans (mf) ve "root mean square" (rms) hesaplamaları yapılmıştır. Dikey sıçrama yükseklikleri çift bacakla sıçramada 29.6±2.8 cm, tek bacak sıçramada ise 16.3±2.3 cm olarak bulunmuştur, izokinetik kuvvet ölçümleri sonucunda: sağ bacak fleksiyon pik tork 60,180 ve 300 o/sn sırasıyla 46.3±9.9, 38.3±9.4 ve 26.7±7.5 Nm; ekstansiyon pik tork 60,180 ve 300 °/sn ise sırasıyla 78.2±12.7, 53.3±12.4 ve 37.4±9.2 Nm olarak ölçülmüştür. Çift bacak ve tek bacak sıçrama yükseklikleri ile sağ biseps femoris rms değerleri arasında istatistiksel olarak anlamlı-ilişki bulunurken (p0.05), izokinetik kuvvet ölçümleri ile EMG verileri arasında anlamlı ilişki saptanamamıştır. Literatürde ritmik cimnastikçiler ve bu yaş grubu ile ilgili çalışmalar oldukça sınırlıdır. Bu çalismanın bulguları sıçrama yüksekliği ile EMG güç spektrumu arasındaki ilişkiyi desteklemektedir. Quadriseps femoris kası EMG değerleri ile kasılma kuvveti arasında ilişki olduğunu bildiren çalışmaların aksine, bu çalışmada quadriseps kasına ait kuvvet verileri ile EMG ölçümleri sıçrama yüksekliği arasında anlamlı ilişki bulunamamıştır. Bu sonuçlar seçilen denek grubunun özelliklerinden kaynaklanmış olabilir