Tranexamic acid has positive effect in early period of tendon healing by stimulating the tumor necrosis factor-alpha and matrix metalloproteinase-3 expression levels.

OBJECTIVES: This study aims to evaluate the effect of tranexamic acid (TXA) application in tendon healing by using its immunohistochemical effects on tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and transforming growth factor-beta (TGF-ß) expression; and to identify if TNF-α, MMP-3, and TGF-ß can be used to monitor and evaluate tendon healing or not in tenotomized rat Achilles tendons. MATERIALS AND METHODS: Twelve male Wistar-Albino rats (age 6-7-month-old; weighing 300-350 g) were used in this retrospective study conducted between November 2016 and May 2017. The rats were divided into two groups with similar weights. The right legs of the rats were determined as the study group (TXA), and the left legs as the control serum physiologic (SP) group. Under anesthesia, bilateral Achilles tenotomy was performed and surgically repaired. 1 mL of TXA was applied locally for the right side and 1 mL of SP was locally applied for the left side. Half of the rats were sacrificed at the third week (right leg-TXA3, left leg-SP3) and the other half at sixth week (right leg-TXA6, left leg-SP6) and tendon samples were taken from the extremities. Immunohistochemical findings of TNF-α, MMP-3, and TGF-ß were evaluated on the basis of the frequency and intensity of staining. RESULTS: In TNF-α and MMP-3 and TXA groups, there was a significant difference in staining compared to SP groups (p<0.05). Regarding TNF-α expression, the total index score in the TXA6 subgroup was higher than the TXA3, SP6, and SP3 subgroups (8, 7, 3, and 4, respectively). Overall scores of TNF-α showed that TXA groups had significantly higher scores when compared to SP groups (p<0.05). In addition, total MMP-3 expression scores were significantly higher in TXA groups than in SP groups, respectively; TXA3: 14, TXA6: 11, SP3: 10, and SP6: 9 (p<0.05). However, the degree of staining with TNF-α was found to be significantly lower than MMP-3 (p<0.05). Immunohistochemical reactivity was not observed with TGF-ß. CONCLUSION: Tranexamic acid has positive effect in early period of tendon healing by stimulating the TNF-α and MMP-3 expression levels. TNF-α and MMP-3 can be used to monitor and evaluate tendon healing.

Histopathological and biochemical evaluation of the effect of Paeoniflorin on the periodontium during and after periodontitis formation in rats.

OBJECTIVES: Appraise the effect of systemic Paeoniflorin (Pae) application on the periodontium during and after induction of experimental periodontitis in the presence of ligature and after its removal. DESIGN: Seventy male Wistar rats were separated into seven equal groups. The first group was reserved as healthy control group (Group 1: no periodontitis, no medication) and experimental periodontitis was induced with ligature in the remaining rats. In experimental periodontitis groups, Pae or saline was administered systemically in three differet periods; during the experimental periodontitis induction (period 1), after experimental periodontitis induction which ligature removed (period 2) or ligature kept in position (period 3). Only, one of the groups acted as the control periodontitis group and received no treatment. Experimental periodontitis groups were as follows; Group 2: medication in period 1, Group 3: periodontitis and no medication, Group 4: medication in period 2, Group 5: saline application in period 2, Group 6: medication in period 3, Group 7: saline application in period 3. Matrix metalloproteinases-9 (MMP-9) levels and interleukin-10 (IL-10) levels were detected biochemically and histomorphometric analyses were performed. These analyses included measurements of the area of alveolar bone, the level of alveolar bone, and attachment loss. RESULTS: Area of alveolar bone and IL-10 levels were higher in the Pae-administered groups; level of alveolar bone, attachment loss, and MMP-9 levels were correspondingly lower (P < 0.05). The beneficial effects at histomorphometrical and biochemical levels of Pae were the strongest in the rats that were administered Pae after the removal of ligature. CONCLUSIONS: Systemically administered Pae had a positive effect on the healing of periodontal tissues. Pae can be used as a new therapeutic agent for periodontal diseases, but microbiology-based studies and more extensive biochemistry-based experimental and clinical studies are needed to address this possibility.

Local application of tranexamic acid affects tendon healing negatively in the late period.

OBJECTIVES: This study aims to evaluate the potential adverse effects of tranexamic acid (TA) on tendon healing. MATERIALS AND METHODS: Twelve male Wistar-Albino rats (weighing 300 g to 350 g) were used in the study. Rats were divided into two groups. Right legs of the rats were determined as the TA group and left legs as the serum physiologic (SP) group. Bilateral Achilles tenotomy was performed and surgically repaired. For the right side, 1 mL of TA and for the left side, 1 mL of SP were applied. Half of the rats were sacrificed at the third week and the other half at the sixth week and tendon samples were collected from the extremities. Histological analyses were performed according to the tendon scoring system (Bonar classification). RESULTS: Tenocyte cell morphology was better in the third week in TA group than in SP group. In terms of colloidal organization, SP groups gave superior results in all weeks. An analysis of total tendon healing scores revealed that the results of the third week TA groups were superior to the results of the sixth week TA groups. Tenocyte morphology and total tendon healing scores of rats in the sixth week TA group were statistically significantly lower compared to the third week TA group (tenocyte morphology p=0.009, total score p=0.041). CONCLUSION: In this study, we detected that locally administered TA has an adverse effect on tendon healing in late period. However, further immunohistochemical and biomechanical studies are needed to support these results.

Rutin ameliorates methotrexate induced hepatic injury in rats.

PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.

Rutin ameliorates methotrexate induced hepatic injury in rats

PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.

The impact of dietary induced hyperparathyroidism on healthy and diseased periodontia: an experimental study in rats.

BACKGROUND AND OBJECTIVE: Nutrition may be a potential modifying factor in periodontal conditions. The present study investigated this phenomenon for dietary induced hyperparathyroidism (dHPT) by revealing the histopathological and histomorphometrical profiles of healthy and diseased periodontia in dHPT. METHODS: Dietary induced hyperparathyroidism was induced in 12 rats by dietary calcium/phosphorous imbalance and 12 rats were fed standard diet (SD). Periodontitis was induced on the right mandibular molar teeth (mmt) of these rats by injecting an endotoxin + saline solution whereas injecting pure saline to the left mmt. Thus, four study groups were created: dHPT + saline (group 1), dHPT + endotoxin (group 2), SD + endotoxin (group 3) and SD + saline (group 4). Histological sections were obtained from the second mmt and examined using light microscope. RESULTS: Group 1 demonstrated inflammatory and degenerative alterations in periodontium without pocket formation. Periodontitis was evident in groups 2 and 3. Group 2 revealed the highest amounts of gingival inflammatory cell and vessel counts (group 2 > group 3 > group 1 > group 4), attachment and bone losses (group 2 > group 3 > groups 1 > group 4) and osteoclast count (group 2 > group 3 > group 1 > group 4) (p < 0.05). CONCLUSION: These results propose that dHPT may impair the health status of periodontium and may worsen the pathobiology of periodontal diseases.

Effects of intramuscular parecoxib administration on vasospasm in an experimental subarachnoid hemorrhage model.

AIM: We examined whether intramuscular parecoxib administration has a preventive or therapeutic effect on vasospasm following experimental subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Twenty New Zealand White Rabbits were assigned randomly to one of four groups. Animals in Group I were not subjected to SAH (control group). Animals in all other groups were subjected to SAH. Animals in Group II received no treatment after SAH induction (SAH group). Animals in Group III received intramuscular parecoxib (diluted with saline) injection at 6 and at 30 hours after SAH (treatment group). Animals in Group IV received only intramuscular saline injection at 6 and at 30 hours after SAH (vehicle group). Animals were euthanized by perfusion and fixation 48 hours after SAH induction. Basilar artery cross-sectional areas and wall thicknesses were measured. Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Basilar artery cross-sectional areas in the treatment group were significantly higher than in the SAH or vehicle group (p<.05). Basilar artery wall thickness in the treatment group was significantly smaller than in the SAH or vehicle group (p<.05). CONCLUSION: Our study revealed that intramuscular administration of parecoxib significantly attenuates vasospasm following experimental SAH.

Effects of risedronate on alveolar bone loss and angiogenesis: a stereologic study in rats.

BACKGROUND: The present study was designed to evaluate the effects of risedronate, one of the most potent bisphosphonates, on alveolar bone resorption and angiogenesis in rats with experimental periodontitis to identify dose-response curves and treatment durations that can be therapeutic for periodontal therapy versus those associated with osteonecrosis of the jaws. METHODS: Thirty-five rats, 25 with experimental periodontitis (groups 1 through 5) and 10 with healthy periodontium (groups 6 and 7), were divided into seven equal groups: group 1 received no treatment; groups 2 and 3 received risedronate, 0.1 and 1 mg/kg, respectively, for 3 weeks; groups 4 and 5 received risedronate, 0.1 and 1 mg/kg, respectively, for 8 weeks; and groups 6 and 7 received 0.9% NaCl for 3 and 8 weeks, respectively. Animals in groups 2 through 7 were administered treatment 5 days per week. After histologic processing, histomorphometric and stereologic analyses were carried out to estimate the number of blood vessels (NBV) and the volumetric densities of bone (Vb), marrow (Vm), osteoblasts (Vob), and osteoclasts (Voc). RESULTS: A total of 0.1 and 1 mg/kg risedronate for 3 weeks (groups 2 and 3) significantly increased Vb and Vob and decreased Vm more prominently in group 2 (P <0.001), whereas 1 mg/kg risedronate for 8 weeks (group 5) induced no significant improvement in these parameters compared to group 1 (P >0.05). No significant decrease in Voc was found in drug-administered groups compared to group 1 (P >0.05). A significant decrease in NBV (P <0.01) and positive correlation between NBV and Vb (r(2) = 0.941; P = 0.006) were found only in group 5. CONCLUSION: A short duration of risedronate administration may be useful in inhibiting bone resorption in periodontitis, whereas excessive dosages of the drug administered in longer durations can lead to impairment of bone formation and angiogenesis.