Einfluss der selektiven Inhibition proinflammatorischer Lipoxygenase auf den osteoporotischen Knochen im Ovariektomodell der Ratte
Influence of the selective inhibition of proinflammatory lipoxygenase on the osteoporotic bone in the ovariectomized rat model
by Marc Hendrik Zimmermann
Date of Examination:2018-03-26
Date of issue:2018-03-23
Advisor:Prof. Dr. Stephan Sehmisch
Referee:Prof. Dr. Stephan Sehmisch
Referee:Prof. Dr. Hubertus Jarry
Referee:Prof. Dr. Rainer Mausberg
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Abstract
English
Osteoporosis is now a serious widespread disease in Germany. Since the population aged and health care costs continuously increased, the treatment of osteoporosis poses a major socio-economic challenge for society. Established treatments, such as the administration of bisphosphonates, however had some negative side effects. As a result, there is a need for research into alternative therapies. As part of Traditional Chinese Medicine, baicalein has been used for centuries for various heart-, circulatory- and bone-diseases. Futhermore, the low toxicity makes baicalein interesting for osteoporosis research. In the present study, the effects of the treatment with baicalein applied at different concentrations on the osteoporotic bone were examined using femur. For this purpose, 61 female rats, which were 3 months old at the start of the trial, were divided into 5 experimental groups. To induce osteoporosis, a bilateral ovariectomy was performed in groups 2 - 5. The unoperated animals of group 1 served as a control group. After 8-week period, the ovariectomized rats developed a severe osteoporosis. Thereafter, treatments with baicalein were performed as follows: in group 3: 1 mg/kg body weight (bw), group 4: 10 mg/kg bw and group 5: 100 mg/kg bw. Baicalein dissolved in dimethyl sulfoxide was administrated by daily s.c. injection. After 28 days all experimental animals were killed by decapitation. The non-drug treated group 2 was designated as an ovariectomized control group. After the biopsy, the femora was subjected to a biomechanical compression test in order to check its mechanical properties. In addition, the bone samples were examined after ashing in terms of their organic and inorganic composition and their calcium and phosphate content. Further, a micro-computed tomographic analysis was performed to examine the trabecular network in the region of the femur head. Evaluation of the results from the biomechanical analysis revealed a significant decrease in the elasticity parameter for the baicalein-treated experimental groups. Furthermore, a slight improvement in the maximal strength was observed in the 1-mg- and 10-mg-baicalein-groups, although the differences were not significant. In ashing analysis, there were no differences between the OVX-control-group and the baicalein-groups in both the organic and inorganic masses. In addition, the values of calcium and phosphate content were very close to each other across groups. Based on the results of the micro-computed tomographic analysis, inhomogeneous results were found in the baicalein-treated experimental groups. While no improvement in the density of the individual bone compartments could be registered, there was an increase in the cortical area around the collum femoris, especially in the 100-mg-baicalein-group. In the area of substantia spongiosa, the therapy with baicalein revealed no advantage over the OVX control group. In the present study it could be shown that the treatment with baicalein had barely measurable influence on the osteoporotic bone. Due to inhomogeneous effects in bone and side effect of s.c. administration further investigations with modified experimental setup (e.g. longer duration, oral administration etc.) are necessary.
Keywords: Baicalein; Osteoporosis; Femur; Rat
Schlagwörter: Baicalein; Osteoporose; Femur; Ratte