Endoplasmic Reticulum Stress in Myometrial Smooth Muscle Cells and Spontaneous Contraction Changes in the Uterus of Dehydroepiandrosterone-induced Polycystic Ovary Syndrome Rats.

Myometrial changes in polycystic ovary syndrome (PCOS) are poorly investigated. Thus, we aimed to investigate endoplasmic reticulum (ER) stress in myometrial smooth muscle cells and changes in spontaneous uterine contraction in PCOS. Twenty-one female Sprague-Dawley rats (21 days old) were divided into control (n = 7), vehicle (n = 7) and PCOS (n = 7) groups. While the control group was not injected subcutaneously, the vehicle group was injected subcutaneously with sesame oil (0.2 ml/day) for 20 consecutive days. The PCOS group was injected subcutaneously with dehydroepiandrosterone (6 mg/100 g/day dissolved in 0.2 ml sesame oil) for 20 consecutive days. Blood samples were collected for the measurement of follicle stimulating-hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) and glucose-regulated protein 78 (GRP78). The mRNA expression of GRP78 in the uterine tissue samples was analysed by quantitative real-time polymerase chain reaction. GRP78 protein expression was assessed by immunohistochemistry. Myometrial smooth muscle cells were examined by transmission electron microscopy. Uterine contractions were evaluated with isolated organ bath experiments. In the PCOS group, T and LH levels increased significantly, although FSH and E2 levels decreased, but this decrease was not statistically significant. Additionally, GRP78 levels increased significantly in the PCOS group. In the PCOS group, the mRNA level, immunostaining intensity of GRP78, and ER damage grade increased, but the uterine tissue calcium levels, and the frequency and amplitude of spontaneous uterine contractions decreased. The results indicated that increased ER stress in myometrial smooth muscle cells may play a causative role in the decreased spontaneous uterine contractions in PCOS.

The effects of topical mafenide acetate application on skin graft survival in bacterial contaminated wounds.

BACKGROUND: Infection related skin graft loss still remains as a common problem even with the use of systemic antibiotics. Mafenide acetate (Sulfamylon) is a topical antimicrobial agent with a wide spectrum of antimicrobial activity. Since mafenide acetate has the ability to penetrate the burn eschar, it was preferred in the treatment of infected full-thickness skin grafts. We investigated the effects of topical Mafenide acetate application on graft survival in an experimental model of contaminated wound beds in rats. MATERIALS AND METHODS: Twenty-eight male Wistar albino rats were included in the study. A full-thickness skin graft (FTSG) was harvested from the back region and the wound bed was inoculated with Pseudomonas aeruginosa. The same FTSG was sutured in place. Rats were divided into 4 groups. In groups 1 and 2, wound care was performed with gauze and hydrofiber dressings respectively. In groups 3 and 4, Mafenide acetate soaked hydrofiber and Mafenide acetate soaked gauze dressings were used respectively. The dressings were closed for 4 days in all groups. The rats in groups 1 and 2 received dressing changes every day. The dressing of the rats in group 3 was changed once every two days. The dressing of the rats in group 4 was changed twice a day. RESULTS: In groups 3 and 4, the graft survival rates decreased significantly from day 7 to day 14 in all groups. Histologically, detachment at the dermoepidermal junction, disorganization of collagen along with increased numbers of fibroblasts and a decrease in graft adhesion to the wound bed were determined in Mafenide acetate-treated groups. CONCLUSION: In rats treated with Mafenide acetate, graft survival was higher on day 7 and gradually decreased towards day 14. Application of a 2.5% solution of Mafenide acetate longer than 7 days on inoculated skin grafts in a rat model causes significant cytotoxicity and graft loss.

Protective effect of paricalcitol in rat testicular damage induced by subchronic 1800 MHz radiofrequency radiation.

In the present study, the possible protective effects of paricalcitol (P) were investigated in testicular damage because of 1800 MHz radiofrequency radiation (RFR) exposure. Male Sprague Dawley rats 8-10 weeks old (n = 28) were randomly divided into four groups as control (C) (n = 7), RFR (n = 7, 1800 MHz RFR 1 h/day for 30 days), P (n = 7, 0.2 µg/kg paricalcitol, 3 times a week for 30 days), and RFR + P (n = 7, 1800 MHz RFR 1 h/day for 30 days +0.2 µg/kg paricalcitol, 3 times a week for 30 days). Testicular tissue was evaluated with histological and biochemical methods. No statistically significant differences were detected between the groups in seminiferous tubule diameters and germinal epithelial thicknesses. While ultrastructural changes were observed in the seminiferous tubule and Leydig cells in the RFR group, these changes were decreased in the RFR + P group. It was found that the Johnsen Score, Ki67, and p63 immunoreactivity scores (IRS), superoxide dismutase (SOD), and catalase (CAT) activities in the RFR + P group were statistically increased as compared to the RFR group and the malondialdehyde (MDA) levels were decreased statistically and significantly. These results show that paricalcitol administration may have an ameliorative effect on testicular damage occurring because of 1800 MHz RFR exposure.

Perifosine and vitamin D combination induces apoptotic and non-apoptotic cell death in endometrial cancer cells.

Endometrial cancer is the most common cancer of the female reproductive system. Combination treatment with specific agents has been widely used as a targeted therapy for cancer. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of varying concentrations of perifosine and vitamin D on the human endometrial cancer cell line (HEC-1A). HEC-1A cells were exposed to perifosine (10 µM, 30 µM), vitamin D (50 nM, 200 nM) and combinations of both for 48 h and 72 h. Monitoring of cell proliferation in a time-dependent manner was performed with the xCELLigence RTCA DP system. The levels of BCL2, BAX and P53 mRNA expression were examined using RT-qPCR. Apoptosis was determined using Annexin V, which were followed by flow cytometry analysis. Ultra-structural morphology of cells was analyzed by transmission electron microscopy (TEM) for 72 h. The anti-proliferative and apoptotic effects of the perifosine+vitamin D combination (30 µM + 200 nM at 48 h and 10 µM + 200 nM at 72 h) on HEC-1A cells were higher than in perifosine and vitamin D alone. It was observed that perifosine has increased the expression of BAX mRNA in HEC-1A cells in a dose-dependent manner. While perifosine+vitamin D combinations increased P53 mRNA expression in HEC-1A cells we did not find any significant change in BCL2, BAX mRNA expression levels. In TEM examinations of HEC-1A cells, perifosine appeared to lead autophagic cell death, whereas vitamin D caused paraptosis-like cell death and combination of perifosine+vitamin D caused apoptotic and non-apoptotic (paraptotic, autophagic and necrotic) cell death. Therefore, it is considered that the combination of both drugs in the treatment of endometrial cancer might be an alternative and effective treatment option through activating the apoptotic and non-apoptotic cell death mechanisms in cancer cells.

Evaluation of the Rho A/Rho-kinase pathway in the uterus of the rat model of polycystic ovary syndrome.

The aim of this study was to investigate the expression of RhoA/Rho-kinase in the uterus and the effect of Rho-kinase inhibitors on uterine contractions of dehydroepiandrosterone (DHEA) induced polycystic ovary syndrome (PCOS) rats. Forty-four female Sprague-Dawley (21 days old) rats divided into three groups: The control group (n = 14, any procedure was not performed), vehicle group (n = 14, 0.2 ml of sesame oil, subcutaneous injection, 20 days) and PCOS group (n = 16, DHEA 6 mg/100 g in 0.2 ml of sesame oil, subcutaneous injection, 20 days). The myometrium thickness and uterine wet weight were assessed. The mRNA and protein expressions of Rho A, the effect of Rho-kinase inhibitors (fasudil and Y-27632) on KCl, carbachol, and PGF2α induced contractions were evaluated in the uterus. In the PCOS group, the myometrium thickness and uterine wet weight significantly increased compared to the control group and vehicle group. The mRNA expression level and the immunoreactive score of Rho A, ROCK 1, ROCK 2 were similar in all groups. In the PCOS group, KCl, carbachol, and PGF2α induced uterine contractions significantly increased compared to the control group and vehicle group. Fasudil and Y-27632 significantly inhibited KCl, carbachol, and PGF2α induced uterine contractions in all groups. In conclusion, the expression of Rho A, ROCK 1, ROCK 2 not changed although myometrium thickness, uterine wet weight and the contractile responses of uterus increased in the PCOS group. The results suggest that the Rho-kinase inhibitors effectively suppressed increased contractions in the PCOS group they might be potential therapeutic agents.

Effect of low-level 1800 MHz radiofrequency radiation on the rat sciatic nerve and the protective role of paricalcitol.

The nervous system is an important target of radiofrequency (RF) radiation exposure since it is the excitable component that is potentially able to interact with electromagnetic fields. The present study was designed to investigate the effects of 1,800 MHz RF radiation and the protective role of paricalcitol on the rat sciatic nerve. Rats were divided into four groups as control, paricalcitol, RF, and RF + paricalcitol. In RF groups, the rats were exposed to 1,800 MHz RF for 1 h per day for 4 weeks. Control and paricalcitol rats were kept under the same conditions without RF application. In paricalcitol groups, the rats were given 0.2 µg/kg/day paricalcitol, three times per week for 4 weeks. Amplitude and latency of nerve compound action potentials, catalase activities, malondialdehyde (MDA) levels, and ultrastructural changes of sciatic nerve were evaluated. In the RF group, a significant reduction in amplitude, prolongation in latency, an increase in the MDA level, and an increase in catalase activity and degeneration in the myelinated nerve fibers were observed. The electrophysiological and histological findings were consistent with neuropathy, and the neuropathic changes were partially ameliorated with paricalcitol administration. Bioelectromagnetics. 39:631-643, 2018. © 2018 Wiley Periodicals, Inc.

GDF9 and BMP15 Expressions and Fine Structure Changes During Folliculogenesis in Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%. AIMS: To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model. STUDY DESIGN: Animal experimentation. METHODS: Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations. RESULTS: The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (p<0.05) in the Polycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively) compared with the control group (33.72±11.22 and 31.12±11.05, respectively) and vehicle group (33.95±10.75 and 29.99±10.72, respectively). Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level. CONCLUSION: These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome.

Effects of ozone therapy on facial nerve regeneration / Efeitos da terapia com ozônio na regeneração do nervo facial

Abstract Introduction: Ozone may promote moderate oxidative stress, which increases antioxidant endogenous systems. There are a number of antioxidants that have been investigated therapeutically for improving peripheral nerve regeneration. However, no previous studies have reported the effect of ozone therapy on facial nerve regeneration. Objective: We aimed to evaluate the effect of ozone therapy on facial nerve regeneration. Methods: Fourteen Wistar albino rats were randomly divided into two groups with experimental nerve crush injuries: a control group, which received saline treatment post-crush, and an experimental group, which received ozone treatment. All animals underwent surgery in which the left facial nerve was exposed and crushed. Treatment with saline or ozone began on the day of the nerve crush. Left facial nerve stimulation thresholds were measured before crush, immediately after crush, and after 30 days. After measuring nerve stimulation thresholds at 30 days post-injury, the crushed facial nerve was excised. All specimens were studied using light and electron microscopy. Results: Post-crushing, the ozone-treated group had lower stimulation thresholds than the saline group. Although this did not achieve statistical significance, it is indicative of greater functional improvement in the ozone group. Significant differences were found in vascular congestion, macrovacuolization, and myelin thickness between the ozone and control groups. Significant differences were also found in axonal degeneration and myelin ultrastructure between the two groups. Conclusion: We found that ozone therapy exerted beneficial effect on the regeneration of crushed facial nerves in rats.

Resumo Introdução: O ozônio pode promover estresse oxidativo moderado, o que aumenta sistemas endógenos antioxidantes. Há determinado número de antioxidantes sendo investigados terapeuticamente para melhorar a regeneração do nervo periférico. No entanto, nenhum estudo anterior relatou o efeito da terapia com ozônio na regeneração do nervo facial. Objetivo: Nosso objetivo foi avaliar o efeito da terapia com ozônio na regeneração do nervo facial. Método: Ao todo, 14 ratos albinos Wistar foram divididos aleatoriamente em dois grupos com lesões experimentais por esmagamento do nervo: um grupo controle, que recebeu tratamento com solução salina pós-esmagamento; e um grupo experimental, que recebeu tratamento com ozônio. Todos os animais foram submetidos a cirurgia na qual o nervo facial esquerdo foi exposto e esmagado. O tratamento com solução salina ou ozônio se iniciou no dia do esmagamento do nervo. Os limiares de estimulação do nervo facial esquerdo foram medidos antes do esmagamento, imediatamente após o esmagamento e após 30 dias. Depois de medir limiares de estimulação do nervo aos 30 dias pós-lesão, o nervo facial esmagado foi excisado. Todas as amostras foram estudadas por meio de microscopia óptica e eletrônica. Resultados: Após o esmagamento, o grupo tratado com ozônio apresentou menores limiares de estimulação do que o grupo da solução salina. Embora isso não tenha significância estatística, é indicativo de maior melhoria funcional no grupo do ozônio. Foram encontradas diferenças significativas na congestão vascular, macrovacuolização e espessura da mielina entre os grupos do ozônio e controle. Diferenças significativas também foram encontradas na degeneração axonal e ultraestrutura de mielina entre os dois grupos. Conclusão: Verificou-se que a terapia com ozônio teve efeito benéfico sobre a regeneração dos nervos faciais esmagados em ratos.

Effects of ozone therapy on facial nerve regeneration.

INTRODUCTION: Ozone may promote moderate oxidative stress, which increases antioxidant endogenous systems. There are a number of antioxidants that have been investigated therapeutically for improving peripheral nerve regeneration. However, no previous studies have reported the effect of ozone therapy on facial nerve regeneration. OBJECTIVE: We aimed to evaluate the effect of ozone therapy on facial nerve regeneration. METHODS: Fourteen Wistar albino rats were randomly divided into two groups with experimental nerve crush injuries: a control group, which received saline treatment post-crush, and an experimental group, which received ozone treatment. All animals underwent surgery in which the left facial nerve was exposed and crushed. Treatment with saline or ozone began on the day of the nerve crush. Left facial nerve stimulation thresholds were measured before crush, immediately after crush, and after 30 days. After measuring nerve stimulation thresholds at 30 days post-injury, the crushed facial nerve was excised. All specimens were studied using light and electron microscopy. RESULTS: Post-crushing, the ozone-treated group had lower stimulation thresholds than the saline group. Although this did not achieve statistical significance, it is indicative of greater functional improvement in the ozone group. Significant differences were found in vascular congestion, macrovacuolization, and myelin thickness between the ozone and control groups. Significant differences were also found in axonal degeneration and myelin ultrastructure between the two groups. CONCLUSION: We found that ozone therapy exerted beneficial effect on the regeneration of crushed facial nerves in rats.

Is mycophenolate mofetil an alternative agent to corticosteroids in traumatic nerve paralysis?

OBJECTIVE: The effects of an immunosuppressive agent, mycophenolate mofetil (MM), were investigated and compared with those of methylprednisolone (MP) and dexamethasone (DXM) on the traumatic nerve function. STUDY DESIGN: This is a randomized controlled animal study. MATERIALS AND METHODS: This experimental study was performed on 84 male Wistar albino rats. The rats were assigned to 12 groups each consisting of 7 animals. The groups were formed according to application of normal-dose DXM (group 1A-B), high-dose MP (group 2A-B), normal-dose MP (group 3A-B), MM (group 4A-B), and MM with high-dose MP combination therapies (group VA-B). Right sciatic nerve dissection was performed, and compound muscle action potential thresholds were recorded. The nerve was traumatized with the compression of a Jeweller forceps for 20 seconds. Posttraumatic thresholds were also recorded. The compound muscle action potential thresholds were recorded in the first and fourth weeks for the assigned groups. Then, the nerve was transected and prepared for electron microscopic and histopathologic examinations. Nitric oxide and malondialdehyde assessments were performed on both tissue and blood samples. RESULTS: Only the MM and MP+MM groups had satisfactory electron microscopic findings and were about to reach the tissue characteristics of the control animals. Despite the electrophysiologic recovery, the DXM group was found to have poor electron microscopic scoring. CONCLUSIONS: Mycophenolate mofetil has been found to be beneficial in the treatment of traumatic nerve paralysis. Although a complementary investigation is needed, this immunosuppressive agent may be an alternative to corticosteroids for the selected cases where steroid therapy is contraindicated.

Electrophysiological, biochemical and ultrastructural effects of radiotherapy on normal rat sciatic nerve.

UNLABELLED: Abstract Purpose: The aim of the present study was to evaluate the electrophysiological, biochemical and ultrastructural changes on the rat sciatic nerve after radiotherapy. MATERIAL AND METHODS: Thirty male Wistar albino rats were divided into three groups as: Control group (n = 10), Group I: 3 months after radiotherapy (n = 10), and Group II: 6 months after radiotherapy (n = 10). Groups I and II were irradiated with a (60)Co gamma source. A dose of 20 Gy in 10 fractions was applied to Groups I and II. Compound motor action potentials (CMAP) were recorded in all groups. Superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) levels were measured in the sciatic nerve of rats using the biochemical methods. Ultrastructural changes were determined by electron microscopy. RESULTS: In Groups I and II, the amplitude of CMAP was significantly lower and the latency was significantly higher than that of the control group. There were no significant differences between Groups I and II regarding the CMAP amplitude and latency. The MDA levels were significantly increased, whereas the SOD and CAT activities were significantly decreased in experimental groups when compared with the control group. However, there were no significant changes in these parameters between Groups I and II. Degeneration in myelinated nerve fibers was observed ultrastructurally only in the experimental groups. Significant changes were observed between the control group and experimental groups in terms of ultrastructural myelin grading score and axonal damage score. No significant differences were found between Groups I and II. CONCLUSIONS: These findings indicated that the dose of 20 Gy in 10 fractions radiotherapy caused neuropathic damages in normal rat sciatic nerve 3 and 6 months after irradiation.

Effectiveness of the biophysical barriers on the peridural fibrosis of a postlaminectomy rat model: an experimental research.

PURPOSE: Long term results after surgical treatment of disc herniation have shown that epidural and/or peridural fibrosis formed during the healing process after surgical intervention. We conducted this experimental study to evaluation of the effectiveness of the bioresorbable barriers (ADCON-L and Seprafilm(®) Adhesion Barrier) on formation of the peridural fibrosis in rat model performed laminectomy. METHODS: Thirty-two male Wistar albino rats 250-350g body weight were distributed into three groups (CONTROL, AL group received ADCON-L; SAB group received Seprafilm(®) Adhesion Barrier). A dorsal laminectomy at L3, L4, L5 was performed, and then except those of the CONTROL group, the experimental material was left on the dura mater. Six weeks later spinal column of all rats was totally removed between the T10 and L5 levels, and peridural fibrosis, and dural adhesions were evaluated histologically and graded. The results were compared statistically by using the chi-square (χ(2)) test. Also three random regions were examined, and the fibroblast cells were counted. The fibroblast count results were statistically analysed by using the One-Way ANOVA test. RESULTS: The variation of histopathological grades was statistically significant regarding the comparison of the all groups obtained from the χ(2) test (χ(2)=16.40; p=0.003). However, the variation in the mean values of the fibroblast count result was not statistically significant obtained from the One-Way ANOVA test (F=2.114; p>0.05). CONCLUSION: Our study results suggest that Seprafilm(®) Adhesion Barrier and ADCON-L can be effective in reducing the prevalence of the postoperative peridural adhesions in rat laminectomy model. On the other hand, the fibroblast densities of the experimental groups were not different between groups. So, we could say that these materials can act as a foreign body in long term period in rat.

Protective effect of trapidil on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury.

OBJECTIVES: Trapidil is an antianginal compound with a broad spectrum of pharmacological activities. In recent years, it has been used successfully to decrease ischemia-reperfusion injury in several organ systems. We evaluated the effect of trapidil on the long-term histologic damage in testicular ischemia-reperfusion injury. METHODS: Adult male Wistar rats were divided into three groups of six rats each. One group underwent 2 h of testicular torsion; one received pretreatment with trapidil before detorsion; and one group underwent sham operation. All rats underwent bilateral orchiectomy 60 days after the experiment. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histological examination of each testis. RESULTS: Testicular torsion-detorsion caused a significant decrease in the mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score in the ipsilateral testes, but not in the contralateral testes. The animals treated with trapidil had a significant increase in these histological parameters as compared to the torsion-detorsion group. CONCLUSION: Trapidil administration before reperfusion may have the potential to decrease the long-term histologic damage that occurs after experimental testicular torsion. Trapidil is used as an antianginal drug and additional clinical studies are required to elucidate the protective role of trapidil in patients with testicular torsion.

Comparison of bony healing and cartilage degeneration following strut grafting and trapdoor procedures in an ovine model.

This experimental study compared bony healing and cartilage degeneration following strut grafting and trapdoor procedures for osteonecrosis of the femoral head in an ovine model. Osteonecrosis and a bony defect were created surgically in 16 hips of 8 Merino sheep, and the index grafting procedures were performed in a second session. Three months after surgery, the hips treated by strut grafting yielded better articular cartilage protection and bony healing compared to the osteonecrosis groups. The trapdoor group yielded better bony healing compared to the rest of the groups, but the grafts and the osteochondral flaps failed to unite with the host bone. These findings indicate elevating the osteochondral flap during the trapdoor procedure injures the cartilage and may cause degeneration.

The effect of tamoxifen on bladder functions and histology, and the role of estrogen receptor beta in a rat chemical cystitis model.

AIMS: The purpose of this study was to investigate the effect of tamoxifen citrate on bladder functions and histology, and also to investigate the role of estrogen receptor beta (ER beta) in a rat chemical cystitis model. METHODS: The study included 37 female Sprague-Dawley rats. Chemical cystitis was induced by intravesical instillation of hydrochloric acid in 32 rats, and the treatment group (n = 15) received daily 0.4 mg/kg of tamoxifen citrate with orogastric tube, and the control group (n = 17) received no treatment. The sham group consisted of five rats having no acid instillation and no treatment. Cystometric studies were performed in all rats at the beginning and end of the experiment. The rats were euthanized at 2 months. The bladders were removed and examined histologically for mast cells, inflammatory cells, and ER beta. RESULTS: The mean maximal bladder volume increased by 73.6% +/- 25.2 in the treatment group and decreased by 7.2% +/- 10.8 in the control group, revealing a significant difference (P = 0.007). The mean bladder compliance increased by 81.2% +/- 25.2 in the treatment group and decreased by 4.8% +/- 12.7 in the control group, revealing a significant difference between the two groups (P = 0.005). ER beta positive cells were significantly lower in the bladders with chronic cystitis than in the sham group (P = 0.038). CONCLUSIONS: Tamoxifen citrate may be an alternative choice, as easy, to other treatment options in the treatment of chronic inflammatory condition to improve deteriorated bladder function. In addition, ER beta may have a role on chronic bladder inflammation in a rat chemical cystitis model.

[The nitrosative effect of peripheral ischemia-reperfusion on lung and preventive of caffeic acid phenethyl ester]. / Periferik iskemi reperfüzyonun akcigerdeki nitrozatif etkileri ve "caffeic acid phenethyl ester" in koruyucu rolü.

Ischemia-reperfusion (IR) is characterized by microvascular disfunction and this involves both direct effected organ and remote organ by systemic inflammatory response. These remote effects of IR are most frequently observed in the lung and cardiovascular system. In this study we aim to determine lung damage which induced IR, and endothelial and microvascular disfunction using nitrosative markers. Previous studies suggest that caffeic acid phenethyl ester (CAPE) has some antioxidant effects. Therefore, we also investigated whether it has a role associated with nitric oxide during IR condition. Twenty-two adult male Wistar rats were divided into three groups: control (n= 7), IR (n= 7), and CAPE + IR (n= 8). 8 h IR period was performed on right hindlimb in the IR and the CAPE with IR group. In the CAPE with IR group, animals received CAPE 10 microM 1 h before the reperfusion. At the end of the reperfusion period, blood, bronchoalveolar lavage (BAL) and lung tissue were obtained, and were used for biochemical and histopathological examination. There was a significantly elevation in serum nitrate, BAL MPO, and leukocyte infiltration in the lung in the IR group compared to the CAPE + IR group. But, serum nitrite and lung 3-NT levels were not different between these groups. While nitrate (p< 0.0001), MPO (p< 0.0001) and leukocyte infiltration (chi2= 27.163, p= 0.0001), reduce by using CAPE before reperfusion, tissue 3-NT levels did not change. In conclusion, peripheral IR leads to systemic inflammatory responses and endothelial disfunction-induced NO production, and these harmful effects may reduced by CAPE.

Inhibition of poly(adenosine diphosphate-ribose) polymerase decreases long-term histologic damage in testicular ischemia-reperfusion injury.

OBJECTIVES: To evaluate the effect of 3-aminobenzamide, an inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), on the long-term histologic damage in testicular ischemia-reperfusion injury. PARP inhibitors have been used successfully to decrease ischemia-reperfusion injury in several organ systems. METHODS: Adult male Wistar rats were divided into four groups of 7 rats each. One group underwent 2 hours of testicular torsion; one received pretreatment with vehicle (dimethyl sulfoxide) before detorsion; one received pretreatment with 3-aminobenzamide, an inhibitor of PARP, before detorsion; and one group underwent a sham operation. All rats underwent bilateral orchiectomy 60 days after the experiment. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histologic examination of each testis. RESULTS: Testicular torsion-detorsion caused a significant decrease in the mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score in the ipsilateral testes (P <0.001), but not in the contralateral testes. The animals treated with 3-aminobenzamide had a statistically significant increase in these histologic parameters compared with the torsion-detorsion group (P <0.01). CONCLUSIONS: The results of this study show that PARP may have a role in the testicular damage caused by ischemia-reperfusion. Administering PARP inhibitors before reperfusion may have the potential to decrease the long-term histologic damage that occurs after testicular torsion.