Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model.

INTRODUCTION: Etanercept has been widely used in autoimmune diseases for blocking tumor necrosis factor α (TNF-α), which is an inflammatory cytokine. The anti-apoptotic and anti-inflammatory effects of etanercept against ischemia/reperfusion (I/R) injury have been shown for several tissues in rat studies, but to the best of our knowledge, there are no reports on its protective effects following similar injury in ovarian tissue. The aim of this study was to investigate whether etanercept has beneficial effects on ovarian I/R injury, as well as on ovarian reserve. MATERIAL AND METHODS: Twenty-four rats were randomly divided into four groups (n = 6/group): sham (laparotomy only); sham + etanercept; I/R; and I/R + etanercept. Ischemia was induced for 3 h by twisting the ovary, and 24 h after detorsion the ovarian tissues were collected to evaluate histopathologic changes, glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) concentrations for oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, caspase-3 activity for apoptosis and ovarian follicle counts. To measure anti-Mullerian hormone (AMH), serum samples were drawn before and after surgery. RESULTS: Tissue GSH and SOD levels were significantly higher, while MDA and MPO levels were significantly lower in the I/R + etanercept group than in the I/R group (p < 0.05, p < 0.01, respectively). Tissue 8-OHdG and caspase-3 activity were significantly lower in the I/R+etanercept group than in the I/R group (p < 0.05, p < 0.01, respectively). Preoperative and postoperative AMH levels were compared and there was a significant reduction in the I/R and I/R + etanercept groups (p < 0.001, p < 0.001). The reduction of AMH in the I/R + etanercept group was significantly lower than in the I/R group. The primordial, preantral and small antral follicle numbers were also significantly higher in the I/R + etanercept group compared to the I/R group (p < 0.001, p < 0.001, p < 0.005, respectively). CONCLUSIONS: Etanercept attenuated inflammation and related oxidative stress and also helped to preserve ovarian reserve following ovarian I/R damage.

Effects of dapagliflozin in experimental sepsis model in rats.

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p<0.05). Dapagliflozin also decreased oxidative stress (MDA) in lung tissue and decreased inflammation (MPO) in lung and liver tissue (p<0.05). Caspase 8 and 9 levels in kidney, lung, and liver tissue were increased (p<0.05) in the dapagliflozin group compared with the sepsis group. According to the histopathological results, sepsis was moderately improved in renal tissue and slightly attenuated in lung and liver tissue with the administration of dapagliflozin. CONCLUSION: Dapagliflozin had a preventive effect on sepsis-induced kidney damage, but the protective effect was mild in lung and liver tissue in the present study.

Etanercept protects myocutaneous flaps from ischaemia reperfusion injury: An experimental study in a rat tram flap model.

Background Being an inevitable component of free tissue transfer, ischemia-reperfusion injury tends to contribute to flap failure. TNF-α is an important proinflammatory cytokine and a prominent mediator of the ischemia-reperfusion injury. Etanercept, a soluble TNF-α binding protein, has shown anti-inflammatory and anti-apoptotic effects in animal models of renal and myocardial ischemia-reperfusion injury. We have designed an experimental study to investigate the effect of etanercept on myocutaneous ischemia-reperfusion injury on transverse rectus abdominis myocutaneous flap model in rats. Methods Twenty-four male Sprague-Dawley rats were divided into 3 groups: In group 1 (sham), the TRAM flap was raised and sutured back without further intervention. In group 2 (control), the flap was raised and the ischemia-reperfusion protocol was followed. In group 3, etanercept (10 mg/kg, i.v.) was administered 10 minutes before reperfusion. At the end of the reperfusion period, biochemical and histolopathological evaluations were performed on serum and tissue samples. Results In the etanercept group the IMA and 8-OHdG levels (p = 0.005 and p = 0.004, respectively) were found significantly lower, and the GSH and SOD levels (p = 0.01 and p < 0.001, respectively) significantly higher in comparison to the control group. The histopathological analysis has revealed a lower degree of hyalinization, degenerated muscle fibers and nuclear change in the etanercept group compared to the control group. Conclusion The results of our experimental study indicate that etanercept offers protection against ischemia-reperfusion injury in skeletal muscle tissue, enhancing the TRAM flap viability. The ability of etanercept to induce ischemic tolerance suggests that it may be applicable in free-flap surgery.

The Effect of Liquid Nitrogen on Bone Graft Survival.

Liquid nitrogen is used in medicine for cancer treatment and tissue preservation; however, bone viability after its application is controversial. This study aims to evaluate both the tissue viability and the clinical and histopathologic findings following liquid nitrogen application with different thawing techniques in rats. Mandibular bone grafts were taken from 45 Wistar rats and freezed in liquid nitrogen for 20 minutes. In the rapid-thawing technique (Rapid Thawing-1, Rapid Thawing-2), the grafts were held for 20 minutes in room temperature; in the slow-thawing technique (Slow Thawing-1, Slow Thawing-2), 20 minutes in -20°C, 20 minutes in +4°C, and 20 minutes in room temperature, respectively. In Rapid Thawing-2 and Slow Thawing-2 groups, autografts were implanted to their origin for 3 weeks and bone staining with India ink was performed and samples taken for histologic examination. The amount of cells and blood vessels and the density of bone canaliculi were significantly reduced in Rapid Thawing-1 and Slow Thawing-1 groups comparing to the Control group. However, the reduction rate was more significant in the Slow Thawing-1 group. Histomorphometric evaluation of the healing autografts after 3 weeks revealed that the decreased amounts of canaliculi were not changed in Slow Thawing-2 group. The study results demonstrated that bone tissue survives after liquid nitrogen treatment regardless of the performed thawing technique; however, slow thawing causes more tissue damage and metabolism impairment.

The effect of Momordica charantia intake on the estrogen receptors ESRα/ESRß gene levels and apoptosis on uterine tissue in ovariectomy rats.

Estrogen or combinational hormone therapy can protect to menopausal symptoms but exogenous estrogen therapy has some potential risks which in turns lead to the appearance of various diseases. In recent years plants with high phytoestrogen content are recommended as therapeutic agents for postmenopausal hormonal treatment. In this research, we investigated the effects of Momordica charantia (MC) on the estrogen production and E2 as well as anti-oxidative and anti-apoptotic role on the ovariectomy rat model. The rats were ovariectomized and fed on 2 g/kg of fruit extra of MC for 30 days by gavage. 17-ß estradiol (E2) and 8-OHdG levels in serum, markers of oxidative damage of ROS and ESRα, ESRß and NF-kB gene levels were measured in uterus horn tissue. Caspase-3, caspase-9, TNF-α, IL-6, IL-10, Bcl-2 and Nf-kB proteins expression were assessed by western blotting. Structural changes in tissue were examined with H&E staining. MC administration also stimulated the E2 production and ESRα/ESRß gene levels and the inhibited oxidative damage. Furthermore, MC treatment enhanced anti-apoptotic and anti-inflammatory process and tissue regeneration. Data herein support that MC directly regulates uterine estrogen response and may serve as a new phytoestrogenic substance for the treatment of post-menopausal symptoms.

Nasal septal turbinate: cadaveric study.

BACKGROUND: Despite the importance of its location, the functional behavior of the nasal septal turbinate (NST) is still not completely understood. Basic histological knowledge is still lacking. The aim of this study was to describe the histological features of the NST and to compare its morphometric features to those of the adjacent nasal septum and the inferior and middle turbinates. METHODS: The study included 50 fresh cadavers. Excisional biopsy specimens of the NST with adjacent posterior septum were collected. In addition, mucosal and submucosal biopsy specimens were taken of the inferior and middle turbinates. Morphometric analysis was performed on five different tissue types: glandular elements, connective tissue stroma, arterial structures, and capillary or venous sinusoids. RESULTS: The mean proportion of venous sinusoids was statistically lower in the nasal septum and NST than in the inferior and middle turbinate. The mean proportion of glandular tissues was higher in the NST than in other regions of the nasal cavity. The mean proportion of arterial tissue was lower in the nasal septum and the NST. Significantly fewer capillary elements were found in the inferior and middle turbinates than in the nasal septum and NST. The mean proportion of connective tissues was lower in the NST than in other regions of the nasal cavity. CONCLUSION: The similar histopathological cell distribution in the middle and inferior turbinate supported a function as an erectile organ, but the findings for the NST pointed to different functional properties of this region.