Protective Effect of Glutathione Administration on Ovarian Function in Female Rats with Cyclophosphamide-Induced Ovarian Damage.

OBJECTIVES: We investigated the potential of glutathione to protect ovarian function in rats exposed to cyclophosphamide by measuring serum anti-Mullerian hormone (AMH) levels, follicle counts, and related parameters. DESIGN: Forty-two adult female Sprague-Dawley rats were randomly divided into six groups and treated with various combinations of cyclophosphamide, glutathione, and sodium chloride. On day 21, the rats were anesthetized, and their ovaries were removed for examination. PARTICIPANTS/MATERIALS, SETTING, METHODS: Histopathological examination, serum AMH concentrations, follicle counts, AMH-positive staining of follicle percentages were analyzed. Statistical analysis was performed using a one-way analysis of variance and Tukey's test, with significance set at p < 0.05. Secondary measures encompassed histopathological examination and percentages of AMH-positive staining of follicles. RESULTS: Significant differences were observed in follicle counts, AMH-positive follicle parameters, and serum AMH concentrations among the six groups. Group 2 (treated with cyclophosphamide) had the lowest primordial, primary, secondary, and antral follicle counts and the highest atretic count. Group 6, treated with cyclophosphamide and 200 mg/kg glutathione, showed improved follicle counts compared to those in group 2. Reducing the glutathione dose to 100 mg/kg was ineffective. LIMITATIONS: This was an experimental animal investigation with a comparatively modest sample size. Experimental studies should be conducted to determine the optimal dosage and duration of glutathione therapy. Information gathered from an experimental animal model may not yield precisely similar outcomes in humans; therefore, additional investigations are necessary to examine the impact of glutathione on women experiencing POI. CONCLUSIONS: The anti-oxidative protective effect of directly administered glutathione was demonstrated for the first time. Low-dose glutathione was ineffective, whereas a high dose yielded significant ovarian protection against cyclophosphamide. Our findings provide valuable insights for supplementing clinical trials on the protective effects of glutathione against ovarian damage.

Comparative effects of the antioxidant glutathione with metformin and Diane-35 on hormonal, metabolic, and inflammatory indicators in a DHEA-induced PCOS rat model.

OBJECTIVE: Comparison of hormonal, metabolic and inflammatory markers of glutathione with metformin and Diane-35 in a rat model of PCOS induced by dehydroepiandrosterone. METHODS: Twenty-five female rats were randomized into four groups. Group 1 was administered a subcutaneous dose of 0.2 ml saline/day. Group 2 was given 0.2 ml of 1% carboxymethyl cellulose (CMC)/day orally for 28 days. A PCOS model was established with DHEA in rats. Group 3 was given 4.5 mg/kg/day of Diane-35 orally dissolved in 1% CMC for 28 days. Group 4 was given 300 mg/kg/day of metformin orally dissolved in 1 ml of saline for 28 days, and Group 5 was administered 100 mg/kg of glutathione intraperitoneally on days 35, 42, and 49. On day 56, the rats were sacrificed. Serum markers and follicle count were examined. RESULTS: Serum IL-6, hs-CRP, insulin, testosterone, SHBG, and MDA values were significantly lower in the glutathione group than in the PCOS group (p = 0.0006, p = 0.023, p = 0.0082, p = 0.0007, p = 0.0048, and p < 0.0001, respectively).The number of all follicles was similar between the control and glutathione groups (p < 0.05). When we compared the other groups with the PCOS group, the number of primary, secondary, atretic, and cystic follicles was significantly lower in the metformin and glutathione groups. The number of primordial and antral follicles was significantly higher than in the PCOS group. CONCLUSIONS: Glutathione plays anti-inflammatory and antioxidant roles, similar to metformin, by lowering serum IL-6, insulin, testosterone, CRP, and MDA levels; decreasing atretic/cystic follicle count; and improving antral follicle count and folliculogenesis in PCOS patients.

Treatment of ovarian damage induced by chemotherapeutic drugs in female rats with G-CSF and platelet-rich plasma(PRP): an immunohistochemical study correlation with novel marker INSL-3.

OBJECTIVE: To assess the impacts of Platelet-Rich Plasma(PRP) and Granulocyte Colony-Stimulating Factor(G-CSF) on a rat model with induced ovarian follicular damage caused by cyclophosphamide(Cy). MATERIALS AND METHODS: Forty-two Sprague-Dawley rats were randomly allocated into seven distinct groups as; Group 1(control): NaCl intraperitoneal (IP) injection was administered on days D1, D7, and D14. Group 2(Cy):Cy IP injection on D1 + NaCl IP injection on D7 and D14 were administered. Group 3(PRP): PRP IP injection on D1,D7 and D14 were administered. Group 4(Cy + PRP):Cy IP injection on D1 and PRP IP injection on D1, D7 and D14 were administered. Group 5(G-CSF): G-CSF IP injection on D1, D7 and D14 were administered. Group 6(Cy + G-CSF):Cy IP injection on D1+ G-CSF IP injection on D1, D7 and D14 were administered. Group 7(Cy + PRP + G-CSF):Cy IP injection on D1+ PRP IP injection on D1,D7 and D14+ G-CSF IP injection on D1,D7 and D14 were administered. Follicular number, histological scores of AMH and INSL3 stained follicles at different stages of follicular development, and serum Anti-Müllerian hormone(AMH) were evaluated. RESULTS: The primary, secondary, and antral follicle intensity scores for AMH-positive staining were most prominent in Groups 3 and 5. There was no significant difference between groups 4, 6 and 7 compared to group 1 in terms of follicule counts and AMH staining. The intensity scores of AMH-positive staining follicles were notably reduced in group 2 compared to groups 4, 6, and 7, with a significant difference (p < .01). Among the groups, group 2 exhibited the least intense antral follicle staining for INSL3, displaying a significant difference(p < .01) compared to the remaining groups. CONCLUSIONS: Autologous PRP and G-CSF might protect ovarian function in the face of ovarian damage caused by Cy-induced effects.

Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model.

RESEARCH QUESTION: Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects? DESIGN: Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated. RESULTS: Significant reductions in the endometriotic implant surface area (P = 0.0213), serum TOS (P = 0.0491), OSI (P = 0.0056), IL-6 (P = 0.0236), TNF-α (P = 0.0083) and peritoneal fluid OSI (P = 0.0401), IL-6 (P = 0.0205) and TNF-α (P = 0.0045) concentrations were observed in the CBD5 group when compared with the saline solution group. Compared with the saline solution group, increased TAS concentrations in serum (P = 0.0012) and peritoneal fluid (P = 0.0145) were found in the CBD5 group. The CBD5 and leuprolide acetate groups were similar regarding inflammatory and oxidative stress parameters of serum and peritoneal fluid samples. The CBD5 group showed significantly lower mean intensity in both surface epithelium and stromal cells for VEGF (both P = 0.002) and only in surface epithelium cells for IL-6 (P = 0.0108), when compared with the leuprolide acetate group. CONCLUSION: Due to its anti-inflammatory, antioxidative and antiangiogenic effects, CBD might be a therapeutic agent candidate for endometriosis.

The Effects of Transcranial Focused Ultrasound Stimulation of Nucleus Accumbens on Neuronal Gene Expression and Brain Tissue in High Alcohol-Preferring Rats.

We investigated the effect of low-intensity focused ultrasound (LIFU) on gene expression related to alcohol dependence and histological effects on brain tissue. We also aimed at determining the miRNA-mRNA relationship and their pathways in alcohol dependence-induced expression changes after focused ultrasound therapy. We designed a case-control study for 100 days of observation to investigate differences in gene expression in the short-term stimulation group (STS) and long-term stimulation group (LTS) compared with the control sham group (SG). The study was performed in our Experimental Research Laboratory. 24 male high alcohol-preferring rats 63 to 79 days old, weighing 270 to 300 g, were included in the experiment. LTS received 50-day LIFU and STS received 10-day LIFU and 40-day sham stimulation, while the SG received 50-day sham stimulation. In miRNA expression analysis, it was found that LIFU caused gene expression differences in NAc. Significant differences were found between the groups for gene expression. Compared to the SG, the expression of 454 genes in the NAc region was changed in the STS while the expression of 382 genes was changed in the LTS. In the LTS, the expression of 32 genes was changed in total compared to STS. Our data suggest that LIFU targeted on NAc may assist in the treatment of alcohol dependence, especially in the long term possibly through altering gene expression. Our immunohistochemical studies verified that LIFU does not cause any tissue damage. These findings may lead to new studies in investigating the efficacy of LIFU for the treatment of alcohol dependence and also for other psychiatric disorders.

Comparison of 3 Cell-Free Matrix Scaffolds Used to Treat Osteochondral Lesions in a Rabbit Model.

BACKGROUND: Various cell-free scaffolds are already in use for the treatment of osteochondral defects (OCDs); however, a gold standard material has not yet been defined. PURPOSE: This study compared the macroscopic, histological, and scanning electron microscopy (SEM) characteristics of Chondro-Gide (CG), MaioRegen (MA), and poly-d,l-lactide-co-caprolactone (PLCL) cell-free scaffolds enhanced with small-diameter microfractures (SDMs) for OCDs in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: In total, 54 knees from 27 rabbits were used in this study. Three rabbits were sacrificed at the beginning of the study to form an intact cartilage control group (group IC). An OCD model was created at the center of the trochlea, and SDMs were generated in 24 rabbits. Rabbits with OCDs were divided into 4 groups (n = 12 knees per group) according to the cell-free scaffold applied: CG (group CG), MA (group MA), PLCL (group PLCL), and a control group (group SDM). Half of the rabbits were sacrificed at 1 month after treatment, while the other half were sacrificed at 3 months after treatment. Healed cartilage was evaluated macroscopically (using International Cartilage Regeneration & Joint Preservation Society [ICRS] classification criteria) and histopathologically (using modified O'Driscoll scores and collagen staining). Additionally, cell-free scaffold morphologies were compared using SEM analysis. RESULTS: ICRS and modified O'Driscoll classification and staining with collagen type 1 and type 2 demonstrated significant differences among groups at both 1 and 3 months after treatment (P < .05). The histological characteristics of the group IC samples were superior to those of all other groups, except group PLCL, at 3 months after treatment (P < .05). In addition, the histological properties of group PLCL samples were superior to those of group SDM samples at both 1 and 3 months after treatment in terms of the modified O'Driscoll scores and type 1 collagen staining (P < .05). Concerning type 2 collagen staining intensity, the groups were ranked from highest to lowest at 3 months after treatment as follows: group PLCL (30.3 ± 2.6) > group MA (26.6 ± 1.2) > group CG (23.3 ± 2.3) > group SDM (18.9 ± 0.9). CONCLUSION: OCDs treated with enhanced SDM using cell-free PLCL scaffolds had superior histopathological and microenvironmental properties, more hyaline cartilage, and more type 2 collagen compared with those treated using CG or MA scaffolds. CLINICAL RELEVANCE: OCDs treated with PLCL cell-free scaffolds may have superior histopathological properties and contain more type 2 collagen than do OCDs treated with CG or MA cell-free scaffolds.

The association of oxidative stress and DNA damage with XRCC1 and XRCC3 polymorphisms in radiology technicians.

Ionizing radiation has widespread use in medicine in the diagnosis and treatment of many medical conditions. Radiology technicians are one group that is occupationally exposed to low doses of radiation. There are questions regarding whether low dose exposure to radiation could have long-term health consequences. Assessing the effect of radiation on genetic material is essential for appraising long-term health results. Hereditary variations in DNA repair genes cause differentiation in individual responses to radiation related health effects. This study aimed to determine oxidative stress and DNA damage, and their relationship to XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms in radiology technicians occupationally exposed to low dose radiation. Peripheral blood samples were collected from 45 radiology technicians and age-matched with 40 healthy control individuals working in office environments. Our results showed that radiology technicians had significantly greater oxidative stress and DNA damage than the control group, and women appeared more susceptible to occupational radiation exposure than men. Individuals with wild-type genotypes for XRCC1 (Arg/Arg) and XRCC3 (Thr/Thr) had less DNA damage. Lower DNA damage levels could be explained by the enhanced capacity to repair low dose radiation induced DNA damage. Further studies are needed to evaluate the role of DNA repair genes in individuals that are occupationally exposed to low dose radiation.

New bone-generative effect of Salvia officinalis L. in the expanded midpalatal suture : An in vivo and in vitro study.

PURPOSE: The aims of this study were to evaluate the effects of systemic administration of Salvia officinalis Linnaeus (L.) leaf extract on new bone formation in the expanded premaxillary suture in rats in vivo and to examine the antioxidant effects and phenolic profile of Salvia officinalis (SO) leaf and root extracts in vitro. METHODS: Fourteen male Sprague Dawley rats were allocated to two groups: SO group (n = 7) and control group (n = 7). An open-loop spring was attached to the upper incisors of each rat to expand the premaxillae. A 5-day expansion period followed by a 12-day retention period was observed. The rats in the SO group received systemic administration of 20 mg SO/kg/day via the orogastric route for 17 days. Histomorphometric examinations were carried out to examine the amount of new bone formation, number of capillaries, and intensity of inflammatory cell response. Immunohistochemical analysis was conducted to examine the number of osteoblasts and osteoclasts. Leaf and root extracts of SO were also analyzed for antioxidant activity and phenolic compounds in vitro. RESULTS: Statistical analysis showed that the following were higher in the SO group than in the control group: new bone formation, number of osteoblasts and osteoclasts, intensity of inflammatory cell response (neutrophils, lymphocytes, and macrophages), and number of capillaries. The major compound identified in SO leaf extract was rosmarinic acid, while luteolin derivatives, salvianolic acid F, and medioresinol were also present. CONCLUSIONS: Salvia officinalis L. from leaf extract provided antioxidant effects and stimulated enhanced new bone formation in the expanded midpalatal suture after maxillary expansion in rats.

Culturing, Freezing, Processing, and Imaging of Entire Organoids and Spheroids While Still in a Hydrogel.

Organoids and spheroids, three-dimensional growing structures in cell culture labs, are becoming increasingly recognized as superior models compared to two-dimensional culture models, since they mimic the human body better and have advantages over animal studies. However, these studies commonly face problems with reproducibility and consistency. During the long experimental processes - with transfers of organoids and spheroids between different cell culture vessels, pipetting, and centrifuging - these susceptible and fragile 3D growing structures are often damaged or lost. Ultimately, the results are significantly affected, since the 3D structures cannot maintain the same characteristics and quality. The methods described here minimize these stressful steps and ensure a safe and consistent environment for organoids and spheroids throughout the processing sequence while they are still in a hydrogel in a multipurpose device. The researchers can grow, freeze, thaw, process, stain, label, and then examine the structure of organoids or spheroids under various high-tech instruments, from confocal to electron microscopes, using a single multipurpose device. This technology improves the studies' reproducibility, reliability, and validity, while maintaining a stable and protective environment for the 3D growing structures during processing. In addition, eliminating stressful steps minimizes handling errors, reduces time taken, and decreases the risk of contamination.

Electromagnetic Waves from Mobile Phones may Affect Rat Brain During Development.

AIM: To investigate the effects of electromagnetic waves (EMWs) from mobile phones (MPs) on rat brains of rats by morphological and biochemical analysis. MATERIAL AND METHODS: EMW was applied for two hours/day until birth in stand-by fetal and EMW fetal groups and postnatal 60 < sup > th < /sup > day in stand-by and EMW groups. The control group was not exposed to MP. On postnatal 60 < sup > th < /sup > day, brain malondialdehyde (MDA) and glutathione (GSH) levels were measured, and western blot analysis was performed to determine glial fibrillary acidic protein (GFAP) content. Hematoxylin and eosin staining and GFAP immunohistochemistry were applied. Trigeminal nerves were examined using the transmission electron microscope. RESULTS: In comparison to controls, rats exposed to MP in stand-by or talk modes had significantly increased neuronal damage in the cortex and hippocampus. Increased MDA levels in the EMW group and decreased GSH levels in the stand-by, EMW fetal and EMW groups were found compared with controls. Increased GFAP content in the EMW group and increased GFAP staining in the EMW fetal and EMW groups compared to controls were observed. EMW group had a significantly decreased number of myelinated axons than control animals. CONCLUSION: The results of this study suggests that 1800 MHz EMWs (SAR=1.79 W/kg) exposure in the prenatal and early postnatal life may lead to trigeminal nerve damage in addition to oxidative stress-induced neuronal degeneration and astroglial activation in the rat brain. Effects seem to be mode related, being more detrimental in groups exposed to MP during talk mode.

Effect of salvianolic acid B on new bone formation in the orthopedically expanded suture.

OBJECTIVES: To determine the effects of Salvianolic acid B (Sal B) on new bone formation in the orthopedically expanded premaxillary sutures in rats. MATERIALS AND METHODS: The sample consisting of Sprague Dawley rats (male, n = 14) was split in half by random selection: the experiment group (Sal B) and the control group. The premaxillary suture of each rat was expanded by bonding an open-loop spring to two maxillary incisors, each end to one tooth. A 5-day expansion period followed by a 12-day retention period was conducted. The 17-day intraperitoneal administration of Sal B was performed daily for the experiment group at a dose of 40 mg/kilo. The trial was completed after sacrificing the rats and dissection of the premaxillae for histological analysis. The amount of new bone, quantity of capillaries and intensity of inflammatory cells were histomorphometrically determined while the quantities of osteoblasts and osteoclasts were determined immunohistochemically. RESULTS: The Sal B group was significantly different from the control group and had greater quantities of new bone, capillaries, inflammatory cells, osteoblasts, and osteoclasts. CONCLUSIONS: Salvianolic acid B displays a positive effect during premaxillary expansion with a greater number of capillaries potentially in association with higher bone formation and improved angiogenesis in rats.

Cholesterol induced autophagy via IRE1/JNK pathway promotes autophagic cell death in heart tissue.

BACKGROUND: Cardiovascular diseases (CVDs), with highest mortality and morbidity rates, are the major cause of death in the world. Due to the limited information on heart tissue changes, mediated by hypercholesterolemia, we planned to investigate molecular mechanisms of endoplasmic reticulum (ER) stress and related cell death in high cholesterol fed rabbit model and possible beneficial effects of α-tocopherol. METHODS: Molecular changes in rabbit heart tissue and cultured cardiomyocytes (H9c2 cells) were measured by western blotting, qRT-PCR, immunflouresence and flow cytometry experiments. Histological modifications were assessed by light and electron microscopes, while degradation of mitochondria was quantified through confocal microscope. RESULTS: Feeding rabbits 2% cholesterol diet for 8 weeks and treatment of cultured cardiomyocytes with 10 µg/mL cholesterol for 3 h induced excessive autophagic activity via IRE1/JNK pathway. While no change in ER-associated degradation (ERAD) and apoptotic cell death were determined, electron and confocal microscopy analyses in cholesterol supplemented rabbits revealed significant parameters of autophagic cell death, including cytoplasmic autophagosomes, autolysosomes and organelle loss in juxtanuclear area as well as mitochondria engulfment by autophagosome. Either inhibition of ER stress or JNK in cultured cardiomyocytes or α-tocopherol supplementation in rabbits could counteract the effects of cholesterol. CONCLUSION: Our findings underline the essential role of hypercholesterolemia in stimulating IRE1/JNK branch of ER stress response which then leads to autophagic cell death in heart tissue. Results also showed α-tocopherol as a promising regulator of autophagic cell death in cardiomyocytes.

The efficiency of ozone therapy and low-level laser therapy in rat facial nerve injury.

PURPOSE: Comparison of low-level laser therapy (LLLT) and ozone therapy (OT) methods for the treatment of facial nerve injury (FNI) in rats, evaluated by histomorphometric measurement analysis. MATERIALS AND METHODS: Thirty rats were randomly divided into control (C), LLLT, and OT groups. The left facial nerves (FNs) of all rats (n = 30) were used in this study. These were held in a surgical clamp for 30 s to create neuropathic damage. The non-injured right FNs of the rats in the control group formed the fourth, sham (S) group in this study (n = 10). Therefore the total number of evaluated samples was 40. The injured FNs of rats in the control group were left to heal spontaneously, whereas LLLT was applied for 21 consecutive days (output 100 mW/cm2 and wavelength 850 nm) and OT (2 ml; 80 µm/ml) once every 2 days for 21 days. RESULTS: After histomorphological evaluation, the OT group revealed statistically significant outcomes following FNI compared with the OT and control groups in terms of branching of nerve fibers (p = 0.003), nerve fiber diameters (p = 0.0398), nerve fiber areas (p = 0.042), and axon numbers (p = 0.0327). Although the LLLT group revealed a better healing process than the control group, the outcome was not statistically significant in terms of branching of nerve fibers (p = 0.6804), nerve fiber diameters (p = 0.7424), nerve fiber areas (p = 0.7048), and axon numbers (p = 0.7588). CONCLUSIONS: OT resulted in statistically significant differences in outcome when compared with the LLLT and control groups, and provided a safe and effective treatment for FNI in rats. OT could therefore be considered as an alternative treatment of FNI. Clinical studies should now be performed to establish whether comparable results can be achieved in humans.

The protective effect of platelet-rich plasma administrated on ovarian function in female rats with Cy-induced ovarian damage.

PURPOSE: We evaluated the protective effect of PRP on ovarian function in female rats with cyclophosphamide (Cy)-induced ovarian damage. METHODS: Thirty-two adult female Sprague-Dawley rats were randomly divided into four groups. Group 1 (control-sodium chloride 0.9%; 1 mL/kg, single-dose ip injection), group 2 (Cy); 75 mg/kg, single-dose ip injection and sodium chloride 0.9% (1 mL/kg, single-dose ip injection), group 3 Cy plus PRP, Cy (75 mg/kg, single-dose and PRP (200 µl, single-dose) ip injection), group 4 (PRP, 200 µl, single-dose ip injection). Primordial, antral, and atretic follicle counts; serum anti-Müllerian hormone (AMH) levels; AMH-positive granulosa cells; and gene expression analysis of Ddx4 were assessed. RESULTS: Serum AMH levels were significantly lower in group 2 compared to groups 1, 3, and 4 (p < 0.01, p < 0.01, and p = 0.04, respectively). A significant difference was found in the primordial, primary, secondary, antral, and atretic follicle counts between all groups (p < 0.01). There was a statistically significant difference in AMH-positive staining primary, secondary, and antral follicles count between the groups (p < 0.01). There was a statistically significant difference in primary, secondary, and antral AMH positive staining follicle intensity score between the groups (p < 0.01). Ddx4 expression in group 4 was highest compared to other groups. CONCLUSION: Our study may provide evidence that PRP could protect ovarian function against ovarian damage induced by Cy. It could lead to improved primordial, primary, secondary, and antral follicle numbers.

Remote myocardial injury: the protective role of fluoxetine.

Aortic cross-clamping-induced ischemia-reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.

Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia rat model.

OBJECTIVE: Efficacy of treatments for benign prostate hyperplasia (BPH) is limited because the disease has complex etiopathogenesis. Recent studies have demonstrated the presence of phosphodiesterase-5 (PDE-5) receptors in prostate tissue. We investigated efficacy of sildenafil citrate in testosteron - induced BPH in rats. MATERIAL AND METHODS: The rats were divided into three groups. Each groups had 7 rats. Group 1 was control group. Testosteron propionate 3 mg/kg/day was injected subcutaneously for two weeks in Group 2. The same procedure was done for Group 3 and sildenafil citrate was added to water at daily doses of 2 mg/kg for two weeks. The rats were euthanized with intraperitoneal pentobarbital. The body weights were measured and the prostates were removed. RESULTS: The mean weights of rats were 288±31.93, 345±23.23 and 294±32.86 g in Groups 1, 2 and 3, respectively. The mean prostate weights of rats were 0.74±0.18, 1.3±0.13 and 0.72±0.24 g in Groups 1, 2, and 3, respectively. Group 2 had statistically significantly higher prostate weights than the other groups (p<0.01). Relative prostate weight is calculated with ratio of prostate weight to body weight. BPH group showed an increase in relative prostate weight compared with other groups with significant difference (p=0.036 and p=0.040). There was statistical difference for acinar area between Group 2 and the others, no significant difference of number of acini, interstitial space and epithelial thickness. Group 2 has more papillary projections per acini than the other groups. CONCLUSION: Favourable effect of sildenafil citrate on dimensions of prostate but not all on histological parameters was observed. We expect that PDE-5 inhibitors might be a treatment option for BPH patients if the studies support our findings in the future.

Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?

PURPOSE: We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage. METHODS: Twenty-four adult female Sprague-Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed. RESULT(S): The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03). CONCLUSION(S): CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.

Correlation between the mechanical and histological properties of liver tissue.

In order to gain further insight into the mechanisms of tissue damage during the progression of liver diseases as well as the liver preservation for transplantation, an improved understanding of the relation between the mechanical and histological properties of liver is necessary. We suggest that this relation can only be established truly if the changes in the states of those properties are investigated dynamically as a function of post mortem time. In this regard, we first perform mechanical characterization experiments on three bovine livers to investigate the changes in gross mechanical properties (stiffness, viscosity, and fracture toughness) for the preservation periods of 5, 11, 17, 29, 41 and 53h after harvesting. Then, the histological examination is performed on the samples taken from the same livers to investigate the changes in apoptotic cell count, collagen accumulation, sinusoidal dilatation, and glycogen deposition as a function of the same preservation periods. Finally, the correlation between the mechanical and histological properties is investigated via the Spearman's Rank-Order Correlation method. The results of our study show that stiffness, viscosity, and fracture toughness of bovine liver increase as the preservation period is increased. These macroscopic changes are very strongly correlated with the increase in collagen accumulation and decrease in deposited glycogen level at the microscopic level. Also, we observe that the largest changes in mechanical and histological properties occur after the first 11-17h of preservation.

Antioxidant and anti-inflammatory effects of curcumin against hepatorenal oxidative injury in an experimental sepsis model in rats.

BACKGROUND: To investigate the effects of curcumin, an antioxidant and anti-inflammatory agent, on free oxygen radicals and lipid peroxidation in an experimental sepsis model, as well as to determine the role of curcumin in preventing hepatorenal tissue damage caused by sepsis. METHODS: The rats were randomly divided into three groups (n=8) as follows: control group (group 1); sepsis group (group 2); and sepsis + curcumin group (group 3). Sepsis was created using the cecal ligation and perforation (CLP) method. Curcumin was administered intraperitoneally (200 mg/kg) in two equal doses just after the perforation and at twelve hours post-perforation. RESULTS: Serum TNF-a and IL-1ß, and tissue MDA and MPO values were higher, whereas tissue GSH and Na+/K+-ATPase values were lower, in group 2 as compared to group 1. These values in group 3 were the inverse of those in group 2. As compared to group 1, histopathological evaluation of group 2 showed damaged hepatocytes, glomeruli, and tubules, whereas the damage was significantly reduced in group 3 as compared to group 2. CONCLUSION: The strong antioxidant and anti-inflammatory effects of curcumin against potential hepatorenal damage were shown using an experimental sepsis model in rats.

The impact of unilateral experimental rat varicocele model on testicular histopathology, Leydig cell counts, and intratesticular testosterone levels of both testes.

PURPOSE: Varicocele, most treatable pathologic condition in male infertility, exerts unfavorable effects on testicular ultrastructure via various mechanisms. In this study we aimed to demonstrate adverse effects of varicocele on both testes. MATERIALS AND METHODS: Twenty one adult male Albino rats were divided into 3 groups. Sham operation was performed for group 1 (control group), and this group of rats were sacrificed 4 weeks later. Experimental varicocele model was performed for group 2 (varicocele group) and these animals were sacrificed 4 weeks after the operation. In group 3 the rats were varicocelectomized 4 weeks later. This group of rats were sacrificed at 4 weeks postoperatively. The level of testicular damage was examined, and serum testosterone and intratesticular testosterone levels were measured. RESULTS: Mean (±SD) damage scores of the right testes of the sham, varicocele, and varicocelectomy groups were 0, 1.64 ± 1.3, and 1.21 ± 0.3, respectively. There was no statistically significant differences between damage scores of groups 2, and 3 (P = .320), relevant scores of both groups were determined to be significantly higher than group 1 (P = .009, and P = .001). Mean (±) damage scores of the left testes of the three groups were detected to be 0.43 ± 1.13, 2.29 ± 1.15, and 1.78 ± 0.39, respectively. The difference between varicocele, and varicocelectomy groups was not statistically significant (P = .112). CONCLUSION: Unilateral varicocele has deleterious effects on both testes. There was no statistically significant difference as for histopathologic recovery following varicocelectomy.