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This study aimed to investigate the effects of systemic irisin hormone application on new bone formation in peri-implant bone defects. After surgically creating peri-implant bone defects in the metaphyseal part of the tibiae of rats, the rats were randomly divided into 2 equal groups: a control group and an irisin group. In the control group, the rats received no further treatment during the 4-week experimental period after the surgery. The rats in the irisin group, 100 ng/kg irisin was administered intraperitoneally 3 days a week during the 8 weeks experimental period after the surgery. At the end of the experimental period, the rats were euthanized. Implants and surrounding bone tissues were collected for histological new bone formation analysis. The Student t test was used for statistical analysis. There were no significant differences between the groups in the histological analysis, new bone formation and fibrosis (P0.05). Also, in the irisin group, there was numerically but not statistically more new bone formation detected compared with the controls. Within the limitations of this study, irisin did not affect new bone formation in peri-implant defects, although the numerical values favored the irisin group.

Objective The molecular and cellular mechanism underlying endometriosis is still under investigation. CypA is one of the inflammatory marker which secreted various type of cell in the inflammatory condition. During the inflammation, CypA exacerbate inflammatory response by the activation of calcineurin signaling that increases the cytokine secretion and tissue degradation in inflammatory region. The aim of this study was to investigate the effect of calcineurin signaling inhibition on the treatment endometriosis in rats. Materials & Methods In the present study, 32 albino-wistar rat were used. All rats were divided into three groups as Cyclosporin A (n = 10), tacrolimus (n = 10) and control group (n = 12). Cyclosporin A group was administered intraperitoneal and tacrolimus group was administered intravenous, total 2 doses at intervals of 2 weeks respectively. All studies lasted for 8 weeks. Processed endometrial tissues will cut at the middle of the tissue samples and embedded into paraffin. Histological sections (5 µm) were stained with Ki-67, Bcl-2, Caspase-3 and VEGF. Results The size of endometriotic focus were 204.7 ± 153.4 mm3, 71.9 ± 85.4 mm3 ve 30.6 ± 36.7 mm3 in control, in CsA and in tacrolimus groups. Compared the control group the size of endometriotic focus was lower in CsA and tacrolimus group (p = 0.002). Microscopically, Ki-67 (p = 0.010) and VEGF (p = 0.007) immunoreactivity were lower in CsA and tacrolimus group than controls. Conclusion The inhibition of calcineurin signaling with CsA and tacrolimus treatment causes regression of endometriotic focus via decreases of endometriotic cell proliferation and angiogenesis in ectopic endometriotic tissue.

The purpose of this study was to investigate the potential side-effects of lead acetate (LA), which is toxic to the nerves, blood and muscles, in the rat brain. The neuroprotective effects of pomegranate juice (PJ) against LA exposure were also observed. The experiment involved 28 male Wistar albino rats aged 12 weeks. These were divided into four groups: Control, PJ, LA and LA+PJ. Stereological techniques were employed to determine hippocampal volume in each rat brain. Biochemical investigations and histopathological examinations were also performed. Analysis demonstrated a significant decrease in hippocampal volume in the LA group compared to the control group (p < .05). The stereology results also indicated that PJ has protective effects when compared with the LA and LA+PJ groups. A significant increase was also determined in malondialdehyde (MDA) levels and glutathione S-transferase (GST) activity in the LA group compared to the control group, in contrast to glutathione (GSH) levels and carboxylesterase (CaE) and acetylcholinesterase (AchE) activities. MDA and GST activity decreased significantly in the LA+PJ group compared to the LA group in contrast to GSH levels and CaE and AchE activities. Histopathological examination revealed a number of degenerative changes in the LA group. Exposure to LA adversely affects the hippocampus on the male rat brain. It might also be suggested that PJ may ameliorate these deleterious effects.

Objectives: The main aim of this study was to investigate the effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats. Methods: Irisin was subcutaneously administered with osmotic minipumps at the dose of 100 ng/kg/day for 28 days and then, the serum levels of asprosin, leptin, glucose and lipid profile were investigated. Results: Irisin infusion increased asprosin levels in male rats (p = .02) but not in female rats. Irisin inhibited obesity-induced high glucose, low-density lipoprotein (LDL), triglyceride (TG) and leptin levels in all groups; however, it did not lead to any change in asprosin levels in both obese female and male rats. Conclusions: It was determined that irisin increased serum asprosin levels and decreased LDL, TG, glucose and leptin levels, and this could indicate a protective role of irisin against obesity development.

WOS:000604486400035 PubMed: 32823415 Purpose: To evaluate the anti-inflammatory effect of cortistatin (CST) in endotoxin-induced uveitis (EIU) model and to compare the results with corticosteroid treatment. Methods: A total of 35 healthy Wistar albino rats were randomly divided into five groups. EIU was induced by a single subcutaneous injection of lipopolysaccharide (LPS). Group I received intraperitoneal (ip) normal saline (NS), Group II received ip 150 mu g LPS plus NS, Group III received ip 150 mu g LPS plus 250 mu g/kg CST, Group IV received ip 150 mu g LPS plus 1mg/kg dexamethasone, and Group V received ip 250 mu g/kg CST only. The aqueous humor was collected 24 h after injection and the infiltrating cells were determined. Moreover, histopathological and immunohistochemical examinations were also performed. Results: The clinical score and infiltrated cell count were reduced in Groups III and IV compared with Group II (P < 0.001). The pathological findings of Groups III and IV were significantly reduced compared with Group II (P < 0.001). These findings were similar between Groups III and IV (P = 1.000). Tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) immunoreactivity in the ciliary body of Group III and Group IV were significantly reduced compared with Group II (P < 0.001). TNF- and IL-1 beta immunoreactivity in the ciliary body of Group III and Group IV were similar compared with Group I and Group V (range of P values was 0.539-0.958). Conclusion: CST administration as a therapeutic agent might ameliorate the severity of intraocular inflammation in uveitis patients. In conclusion, effect of CST and dexamethasone in EIU model was comparable.

Phoenixin-14 (PNX-14) and nucleobindin 2 (NUCB2)/nesfatin-1 are regulatory neuropeptides expressed in the hypothalamus. These neuropeptides can be effective in hormonal regulation of the hypothalamo-pituitary-gonadal (HPG) axis and reproductive functions. In the present study, the distribution of PNX-14 and NUCB2/nesfatin-1 in the hypothalamus, pituitary, ovary, and uterus tissues during the phases of the estrous cycle in female rats was investigated. Eighteen Wistar Albino rats determined among animals showing regular estrous cycle by vaginal smear method were divided into three groups: proestrus (Group I), estrus (Group II) and diestrus (Group III). Serum gonadotropin-releasing hormone (GnRH), plasma PNX-14, and NUCB2/nesfatin-1 concentrations were the highest, moderate, and lowest in estrus, diestrus, and proestrus phases, respectively. PNX-14 immunoreactivity in the supraoptic and arcuate nuclei of the hypothalamus and NUCB2/nesfatin-1 immunoreactivity in the paraventricular nuclei were particularly evident in the estrus phase. These neuropeptide immunoreactivities were decreased in different cells of anterior pituitary during proestrus compared with those during estrus and diestrus. PNX-14 immunoreactivity in the ovary, especially during the estrus phase, was diffuse and intense in the granulosa and luteal cells and oocytes, and it was few and weak in theca cells. In addition, NUCB2/nesfatin-1 immunoreactivity was abundant and strong in granulosa and luteal cells, theca and interstitial cells, and oocytes during estrus. In the estrus phase, PNX-14 immunoreactivity was strong in the glandular epithelial cells and stromal cells of the endometrium, also NUCB2/nesfatin-1 immunoreactivity was strong in the epithelial and glandular epithelial cells. As a result, when the estrous cycle was evaluated, it was concluded that the changes in the distribution of PNX-14 and NUCB2/nesfatin-1 at all phases were related to GnRH and that these neuropeptides showed the highest immunoreactivity especially in the HPG axis and uterus tissues of estrus rats.

Neuropathic pain is primarily caused by nervous system lesions or dysfunction. Evidence strongly suggests that obesity, diabetes and cancer are common in chronic pain conditions, and pain complaints are common in these individuals. Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal modelsMouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively. Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50 °C and 4 °C respectively) and mechanical pain (Von Frey test) tests at baseline and 30, 60, 120 and 180 minutes after asprosin administration. Serum level of asprosin was quantified by ELISA. In all three neuropathic pain models (STZ, OXA and CCI), asprosin administration significantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. Asprosin levels were significantly lower in three types of neuropathic pain compare to controls (p < 0.05). The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.

This study aimed to conduct a biomechanical investigation of the effects of systemic irisin hormone application on the osseointegration of titanium implants in rat tibias. After surgical implementation of titanium implants in the metaphyseal part of the tibiae of rats, the rats were randomly divided into 2 equal groups: control group (n = 10) and irisin group (n = 10). After surgery in the control group, the rats received no further treatment during the 4-week experimental period. The rats in the irisin group were given 100 ng/kg irisin every day for the 4-week experimental period after surgery. At the end of the experimental period, the rats were euthanized. Implants and surrounding bone tissues were collected for biomechanical (Newton) bone implant connection analysis. The Student t test was used for statistical analysis. There were no significant differences in the biomechanical osseointeration values (Newton) of the groups (P > 0.05, P = 0.59). Also, in the irisin group, there was numerically but not statistically more bone implant connection than in the controls. Within the limitations of this study, irisin did not affect the osseointegration of titanium implants.

Introduction: Obesity is known to cause sexual dysfunction including erectile dysfunction and poor semen quality. Lifestyle modifications such as exercise have increasingly been more recognized to lower the likelihood of having sexual dysfunction or infertility in obese men. In this context, as an exercise-mimetic hormone, irisin has a potential to improve obesity-related reproductive dysfunctions. We aimed to elucidate possible effects of irisin on high-fat diet (HFD)-induced reproductive dysfunction in obese male rats. Methods: Rats were divided into four groups: vehicle, irisin, obese, and obese + irisin. The rats in obese and obese+irisin groups were fed with HFD (60% kcal fat) pellets for 12 weeks to induce obesity, and then obesity-induced sexual dysfunction was confirmed by the sexual behavior test (SBT). Irisin and obese+irisin groups received irisin (100 ng/kg/day) infusion by an s.c. osmotic minipump for 4 weeks after HFD-induced obesity was formed. Results: Irisin did improve a number of measures of copulation, including penile erection, ejaculation, and sexual performance, and also improved sperm morphology and motility and decreased fat-induced testicular damage. It decreased serum leptin levels. On the other hand, irisin did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. It also increased gene expression of tyrosine hydroxylase (TH) and adrenoceptor alpha 1A (ADRA1A) in the medial preoptic area (mPOA) and nucleus accumbens (NAc). Conclusion: Irisin provided a marked enhancement of HFD-induced decrease in libido, potency, sexual performance, and erection in SBT. Taken together, our results emphasize that irisin has a restorative and improver role in HFD-induced reproductive dysfunctions in obese male rats.

Sexual dysfunction is a common clinical condition due to different causes including the use of selective serotonin reuptake inhibitors (SSRI). Especially, SSRI paroxetine is known to cause numerous types of sexual dysfunction in men. There is growing interest in exercise as a non-pharmacological approach for the treatment of SSRI-induced sexual dysfunction. With these in mind, we investigated the effects of irisin, which is a recently detected exercise-linked hormone, on paroxetine-induced sexual dysfunction in male rats. Our findings showed that circulating irisin levels were lower in paroxetine-induced sexual dysfunction in male rats (20 mg/kg/day for 8 weeks by oral gavage than in vehicle-treated rats). In addition, results from sexual behavioral tests revealed that subcutaneous irisin perfusion (100 ng/kg/day via mini-osmotic pumps for 28 days) ameliorated sexual motivation and copulatory performance in sexually impaired male rats treated with paroxetine. The significantly reduced serum testosterone levels and α1-adrenoceptors (ADRA1A) and tyrosine hydroxylase gene (TH) expression levels in the nucleus accumbens (NAc) in paroxetine-induced sexually dysfunctioning male rats were markedly increased following irisin exposure. Similarly, the expression levels of ADRA1A and TH in the medial preoptic area (mPOA) significantly increased in male rats co-administered with paroxetine and irisin compared to the vehicle-treated male rats. These results demonstrate that irisin may be a therapeutic modality that mimics/supports the beneficial effects of exercise for improving SSRI-associated sexual dysfunction in men through increase in serum testosterone levels and increased expression of α1-adrenoceptors and TH in the NAc and mPOA associated with sexual motivation and copulatory behaviors.

The purpose of this study was to investigate the effects of treadmill exercise training on obesity-induced behavioral changes in high-fat diet (HFD)-induced male rats. In this study, 40 male Sprague-Dawley rats were divided into 4 groups after they were weaned: Control (C), Exercise (E), Obese (O) and Obese + Exercise (O + E). For the obesity model % 60 high-fat diet were applied. After obesity was induced, rats were either moderate aerobic exercise (treadmill running) trained or left untrained. Different tasks to assess spatial learning and memory (Morris water maze test (MWMT)), depressive-like behavior (forced swimming test(FST), tail suspension test (TST) and anxiety-like behavior (light-dark test (LDT) and open field test (OFT)) were conducted. Exercise caused a significant reduction in duration of immobility in the O group in FST and the decrease in immobility in the O + E rats in TST. The O + E rats demonstrated a significant increase in the time spent in the light box as compared to the O group in the LDT. The O + E rats did not show any behavioral alterations as compared to all the other groups in the OFT. In the O + E group, there was a significant increase in the time spent in the target quadrant compared to the O group in the MWMT. Our results support that treadmill exercise could improve cognitive, depressive-like, anxiety-like behavioral changes in the HFD-induced obese rats.

This study examined the effects of different levels of chronic restraint stress on bone-titanium implant contact in rats. This study included 32 adult female Sprague-Dawley rats. The machined surface titanium implants were surgically placed into the metaphyseal region of the rat tibias. Next, the rats were divided randomly into 4 groups, namely, control (CNT) (n = 8), low-restraint stress (LRS) (n = 8), medium-restraint stress (MRS) (n = 8), and high-restraint stress (HRS) (n = 8) groups. The rats in the CNT group received only the titanium implants surgically but did not receive any further treatment during the experimental period of 30 days. The rats in the LRS, MRS, and HRS groups were applied restraint stress for 1, 2, and 4 hours, respectively, daily for 28 days starting from day 2 after the surgery. At the end of the study period, the rats were sacrificed and their implants and the surrounding bone tissues were harvested for performing nondecalcified histological analysis. Moreover, blood samples were collected from the rats and were centrifuged for analyzing serum cortisol levels. Serum cortisol levels of the rats in the LRS, MRS, and HRS groups were higher than those of the rats in the CNT group (P 0.05). Moreover, serum cortisol levels of the rats in the HRS group were higher than those of the rats in the MRS and LRS groups (P 0.05). The extent of bone-implant contact was lower in the rats in the HRS group than in the rats in the CNT and LRS groups (P 0.05). These data suggest that the application of 4-hour chronic restraint stress during the 28-day experimental period impaired the bone-implant contact.

Amaç: Bu çalışma; organoklorlu (Endosulfan) ve pyrethroid (Cypermethrin) pestisitler ile herbisitlerin (2,4-D ve Trifluralin) Hershberger metodu ile peri-pubertal erkek sıçan modelinde serum LH ve FSH düzeyleri ile androjen duyarlı dokular üzerine androjenik ve anti-androjenik etkilerini araştırmak amacıyla planlandı.Gereç ve Yöntem: Çalışmada 56 adet peri-pubertal 42 günlük erkek Sprague Dawley sıçan kullanıldı.İlk grup sham kastrasyon olarak ayrıldı. Geriye kalan 49 adet sıçan kastre edildi. On günlük iyileşme süresinin sonunda sıçanlar yedi gruba daha ayrıldı: Kastrasyon grubu; Testosteron propiyonat (TP) grubu; TP+Flutamide grubu; TP+Endosulfan grubu; TP+2,4-D grubu; TP+Cypermethrin grubu; TP+Trifluralin grubu. Son uygulamadan 24 saat sonra sıçanlar dekapite edilerek kan örnekleri toplandı. Tüm hayvanların prostat bezi, bulbouretral bezleri, seminal vezikülleri ve musculus levator ani (mLA) diseke edilerek tartıldı. Serum LH, FSH ve testosteron düzeyleri ELISA yöntemi ile belirlendi.Bulgular: Kastrasyon, tüm androjen-duyarlı doku ağırlıklarında azalmaya neden olurken (p0.05). 2,4-D, Cypermethrin ve Trifluralin serum FSH düzeylerinde anlamlı artışa yol açarken; serum LH düzeylerindeki artış sadece Trifluralin grubunda istatistiksel olarak anlamlı idi. Sonuç: Çalışmadan elde edilen bulgular, Hershberger metodunda Endosulfan, Cypermethrin ve Trifluralin’in bulbouretral bez üzerinde anti-androjenik; 2,4-D’nin ise vesicula seminalis üzerinde androjenik etkilere sahip olduğunu göstermiştir. Bu çevresel kirleticilerin erkek üreme fonksiyonlarını olumsuz yönde etkileyebileceği öngörülebilir., Aim: This study was aimed to investigate the androgenic and anti-androgenic effects of organochlorid (Endosulfan) and pyrethroid (Cypermethrin) pesticides and herbicides (2,4-D and Trifluralin), on serum LH and FSH levels and androgen-sensitive tissues in peri-pubertal rat model with Hershberger assay. Material and Method: 56 peri-pubertal 42 days old Sprague Dawley rats were used in the study. The first group was separated as sham castration. The remaining 49 rats were castrated. After 10 days recovery period, rats were divided into further seven groups: Castration group; Testosterone Propionate (TP) group; TP+Flutamide group; TP+Endosulfan group; TP+2,4-D group; TP+Cypermethrin group; TP+Trifluralin group. 24 hours after the last application, rats were decapitated and blood samples were obtained. Prostate, bulbourethral gland, vesicula seminalis and musculus levator ani (mLA) were dissected and weighed. Serum LH, FSH and testosteron levels were determined with ELISA. Result: Castration caused significant reduction in all androgen-sensitive tissue weights n(p0.05). 2,4-D, Cypermethrin and Trifluralin significantly increased serum FSH levels; but the increase in serum LH levels was only significant in Trifluralin group. Conclusion: Data obtained from this study showed that 2,4-D has androjenic effects on vesicula seminalis whereas Endosulfan, Cypermethrin and Trifluralin have anti-androgenic effects on bulbourethral gland. It can be suggested that, these environmental pollutants could affect male reproductive functions negatively.

We aimed to evaluate the effects of black carrot extract on testicular carboxylesterase (Ces) activity, malondialdehyde (MDA), glutathione S-transferases (GST) and reduced glutathione (GSH) in male rats exposed to bisphenol A (BPA). Adult Wistar albino male rats were divided into 4 groups as follows (n = 7/group): control, BPA, black carrot and BPA+Black carrot. Testicular Ces, MDA, GST and reduced GSH were analyzed by using a spectrophotometer system. Testicular Ces activity was significantly lower only in the BPA group than the control group (p < 0.001). Testicular MDA concentrations were higher only in the BPA group compared with the control group (p < 0.001). Reduced GSH level was higher in the black carrot and BPA+Black carrot groups than the control group (p < 0.05). GST activity was lower in the BPA group in comparison to the control group (p < 0.05). In the black carrot and BPA+Black carrot groups, the GST activities were higher than the control group (p < 0.001). Our results showed BPA suppresses testicular detoxification activity and increases lipid peroxidation in rats. We observed that black carrot extract has a beneficial effect on the toxic and oxidative stress-related parameters caused by BPA exposure.

Objectives Methotrexate (MTX) is an anticancer drug used in chemotherapy. MTX was known for its toxic effects involving most of the organs including testis. Bee pollen is healthy food for human and has antioxidant effect. We intended to determine protective effect of bee pollen against testicular injury caused by MTX in rats. Methods Thirty-two adult Sprague Dawley male rats were used, and 4 groups were formed: control, MTX, pollen, and MTX + pollen. Rats were given pollen at a dose of 400 mg/kg with intragastric gavage for 10 days. On day 7, MTX was administered a single dose of 30 mg/kg ip. Serum testosterone and LH, tissue MDA level, and SOD and CAT enzyme activities were examined. In addition, spermatological parameters were evaluated. Results MDA level and SOD activity increased while testosterone level decreased significantly in the MTX group compared to the control group. In the MTX + pollen group, MDA level and SOD activity decreased while testosterone level increased. There was no significant change in CAT activity and LH values. Abnormal sperm ratio decreased in the MTX + pollen group compared to the MTX group. Conclusions Our results suggest that bee pollen has a healing effect on reproductive parameters in testicular damage caused by MTX.

Objectives Reproduction is one of the physiological functions that are often negatively affected by chronic stress. We aimed to examine effects of two distinct 7-day chronic immobilization stress (IMO) models on gonadotropins levels and depression-like behaviors in female rats. Methods Adult Wistar albino female rats were divided into three groups as follows (n=7 for each group): control, IMO-1 (45 min daily for 7-day) and IMO-2 (45 min twice a day for 7-day). Neuropsychiatric behaviors were determined by using forced swimming test (FST) and open field test (OFT). Gonadotropins were analyzed using ELISA tests. Results In FST, swimming was lower, and immobility was higher in the IMO-1 group and IMO--2 group. Climbing score of the IMO-2 group was higher compared to the control group. In OFT, there was no significant alteration in the mean velocity, total distance, duration of time spent in the central area and duration of latency in the central area between the stress groups and the control group. Final body weight and percentage of body weight change were lower in both stress groups. The follicle-stimulating hormone level was lower only in the IMO-2 group, and the luteinizing hormone concentrations were significantly lower in the IMO-1 group and IMO-2 group. Conclusions Our results indicated that depression-like behaviors increased, and gonadotropins decreased in the female rats exposed to 7-day chronic IMO.

The aim of the study was to examine possible impacts of paroxetine and agomelatine on the levels of some components that constitute the seminal vesicle fluid. As a second purpose, it was also aimed to examine how possible negative effects induced by paroxetine on seminal vesicle fluid components were affected by kisspeptin and RF9 (an RFamide-related peptide antagonist, RFRP). Forty-two male rats, aged 21 days, divided into six groups; control, sham, paroxetine, agomelatine, paroxetine + kisspeptin and paroxetine + RF9. Paroxetine (3.6 mg/kg) and agomelatine (10 mg/kg) were administrated by oral gavage. Kisspeptin (1 nmol) and RF9 (20 nmol) were administered intracerebroventricular (i.c.v). The experiments were ended on post-natal 120 days; fructose, vitamin E, sodium, potassium and magnesium levels were measured in seminal vesicle fluid. Fructose, vitamin E, magnesium and potassium levels were significantly decreased in seminal vesicle fluid from the rats treated with paroxetine but did not show significant differences following agomelatine administration. The co-administration of kisspeptin or RF9 with paroxetine prevented the paroxetine-induced negative effects on seminal vesicle fluid components. These results suggest that reduction in sperm fertilising ability caused by changes in seminal vesicle fluid can be seen in long-term antidepressant use. RF-9 and kisspeptin might have positive effects on long-term antidepressant use-induced infertility.

Physical exercise and body muscle/fat mass are known to affect the endocrine system, puberty onset and reproductive health. However, the potential effects of irisin, an adipo-myokine and exercise-induced hormone, have not yet been fully elucidated on reproductive maturation. Therefore, the present study aimed to determine the effects of irisin administration on pubertal maturation and reproductive system in female and male rats. Daily i.p. injection of irisin (100 ng/kg; from postnatal day 21 for about 10 weeks) delayed the ages at the vaginal opening (as an external index of puberty onset) and first estrus. Furthermore, continuous administration of irisin to female rats caused a significant decrease in serum follicle-stimulating hormone levels and an increase in serum luteinizing hormone and 17β-estradiol levels, as well as causing histopathological changes in the ovarian tissue. On the contrary, irisin administration to male rats did not modify the timing of puberty, as estimated by age at preputial separation. However, chronic exposure to irisin produced significant increases in serum luteinizing hormone and testosterone levels and also sperm concentration and seminiferous tubule diameter in male rats. In conclusion, irisin exposure has different effects on both pubertal maturation and reproductive system in female and male rats. The present findings reveal that chronic irisin exposure may lead to disorders in the female reproductive system and may have androgenic potential on the hypothalamic-pituitary-gonadal axis in males.

Objective: The purpose of the present study was to investigate in vitro the effect of agomelatine, an analog of melatonin, on KCl-stimulated contractions in duodenum, jejunum, ileum, and colon in rats. Material and methods: A total of 7 adult Wistar Albino female rats were used in the study. After the rats were decapitated without anesthesia, duodenum, jejunum, ileum, and colon strips were prepared and placed in the organ bath. Agomelatine was applied in doses of 100, 200, and 1000 μM to the strips that were contracted with KCl (80 mM). Then, 1000 μM agomelatine was applied after preliminary treatment of melatonin receptor antagonist luzindole (1 μM) to investigate the action mechanism of agomelatine on intestinal smooth muscles. The records were analyzed before and after each dose, and frequency, peak to peak (P-P) and area values were compared. Results: Agomelatine inhibited the KCI- induced contractions in duodenum, jejunum, ileum, and colon strips in a dose-dependent manner. Depending on the agomelatine application, the frequency, “P-P”, and the area values under the curve decreased at statistically significant levels (p

Melatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10µM melatonin, and Pinealectomy+100µM melatonin. IFN-γ, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-γ levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+10µM melatonin group, IFN-γ and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100µM melatonin caused a decrease in levels of IFN-γ in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and/or melatonin affect IFN-γ and IL-10 levels in the thymus gland.

Ebru Celik Kavak,1 Funda Gulcu Bulmus,2 Ozgur Bulmus,3 Salih Burcin Kavak,1 Nevin Kocaman4 1Department of Obstetrics and Gynecology, 2Vocational School of Health Services, 3Department of Physiology, 4Department of Histology and Embryology, School of Medicine, Firat University, Elazig, Turkey Aim: The aim of the present study was to assess the protective effects of magnesium sulfate (MgSO4) on ischemia/reperfusion (I/R) induced ovarian damage in a rat ovarian torsion model.Methods: Forty-two female Sprague Dawley rats were included in the study. They were divided into six groups as Group 1, sham; Group 2, bilateral ovarian torsion; Group 3, bilateral ovarian torsion–detorsion; Group 4, MgSO4–sham; Group 5, MgSO4–bilateral ovarian torsion; Group 6, bilateral ovarian torsion–MgSO4–detorsion. Both torsion and detorsion periods lasted 3 hours. In Groups 4, 5 and 6, MgSO4 (600 mg/kg) was administered by intraperitoneal route 30 minutes before sham operation, torsion and detorsion, respectively. At the end of the study period, both ovaries were removed. One of the ovaries was used for histopathological analyses and the other for biochemical analyses.Results: In the torsion–detorsion group, all the histopathological scores were higher compared to the sham and torsion only group (p

Purpose: The aims of this study were to evaluate the effects of decorin (DCN) in rat oxygen-induced retinopathy (OIR) model and to compare the results with those of bevacizumab. Methods: Twenty-eight newborn Sprague–Dawley rats were randomly divided into four groups. Group I (control): normoxia plus intraperitoneal (ip) normal saline (NS), Group II (sham): OIR plus ip NS, Group III (DCN): OIR plus ip 0.1 mg/kg DCN, and Group IV (bevacizumab): OIR plus ip 2.5 mg/kg bevacizumab. The OIR model was induced by cycling the oxygen concentration between 50% and 10% every 24 h for 14 days following their birth. In all groups, injections were administered on postnatal day (PD) 15. All animals were sacrificed and their right eyes were enucleated on PD 18. The nuclei of neovascular endothelial cells on the vitreal side of the inner limiting membrane were counted, and vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF)-α immunoreactivity were detected in histopathological and immunohistochemical examinations. One-way analysis of variance and post hoc Tukey tests were used for statistical analyses of the data. Results: In Groups II, III, and IV, the mean neovascular cell nuclei counts were 13.14 ± 1.34, 6.57 ± 1.51, and 6.71 ± 1.49, respectively. The mean neovascular cell nuclei count was significantly reduced in treatment groups compared with sham group (P < 0.001). In immunohistochemical staining, the immunoreactivity of VEGF was 0.07 ± 0.02, 0.97 ± 0.21, 0.37 ± 0.12, and 0.23 ± 0.17, respectively. Likewise, immunoreactivity of TNF-α was 0.02 ± 0.02, 1.11 ± 0.36, 0.37 ± 0.13, and 0.62 ± 0.21, respectively. VEGF and TNF-α immunoreactivity increased markedly in the sham group compared with those in the control group (P < 0.001). VEGF and TNF-α immunoreactivity of treatment groups decreased significantly compared to sham group (P < 0.001). Conclusion: The beneficial effects obtained by DCN administration in OIR model were comparable to the effects of bevacizumab.

This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone–implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21-90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.

This study aimed to investigate the effects of different doses of systemic melatonin application on new bone formation during mandibular distraction osteogenesis (DO) in rats. Mandibular DO was performed on 30 adult female Sprague-Dawley rats, which were randomly divided into three groups: control group (CNT), melatonin dose 1 (MLT-D1), and melatonin dose 2 (MLT-D2). A five-day latent waiting period and a ten-day distraction phase followed the surgery. After the surgery, rats from the MLT-D1 and MLT-D2 groups received 25 and 50 mg/kg melatonin, respectively, at 7, 14, 21, 28, and 35 days. The animals were euthanised 28 days after distraction, i.e. at 43 days after surgery. Histological and histomorphometric analyses revealed that the distracted bone area was completely filled with new bone formation in all three groups. The MLT-D2 group exhibited the most new bone formation, followed by MLT-D1 and CNT. The melatonin groups had more osteoclasts than the CNT (p < 0.05). The number of osteoblasts was higher in the melatonin groups than in the CNT group, and the MLT-D2 had more osteoclasts than the MLT-D1 group (p < 0.05). Finally, the osteopontin (OPN) and vascular endothelial growth factor (VEGF) levels were higher in the melatonin groups than in the CNT group, and the MLT-D2 had higher OPN and VEGF levels than the MLT-D1 (p < 0.05). This study suggests that systemic melatonin application could increase new bone formation in DO.

Objectives This study aimed to investigate the effects of chronic restraint stress on the osseointegration of titanium implants. Materials and Methods Twenty adult male Wistar albino rats were used in the study. After surgical insertion of titanium implants into the metaphyseal part of the tibial bone, rats were randomly divided into two groups: a control group (CNT group) and an experimental restraint stress group (RS group). In the CNT group, titanium implants were inserted surgically, and rats received no further treatment during the 47-day experimental period. In the RS group, restraint stress was applied for 3 hours per day for 45 days, beginning 2 days after implant surgery. Weight of the rats was measured prior to surgery and at the end of the study to analyze the effects of stress. At the end of the experimental period, rats were euthanized, and implants and surrounding bone tissues were used for undecalcified histological analysis. Serum cortisol levels were assessed in cardiac blood samples from the rats following centrifugation. Results Average weight of rats in the RS group was lower than that of rats in the CNT group after the experimental protocol had been completed (P0.05). Conclusion The data analyzed in this study suggest that chronic restraint stress did not adversely affect rats during a 45-day osseointegration period.

Melatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10µM melatonin, and Pinealectomy+100µM melatonin. IFN-γ, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-γ levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+10µM melatonin group, IFN-γ and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100µM melatonin caused a decrease in levels of IFN-γ in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and/or melatonin affect IFN-γ and IL-10 levels in the thymus gland.

Nitrofurantoin is a drug used in the antibacterial treatment of urinary tract infections (UTIs) for over 60 years. The aim of our study was to investigate the possible effects of nitrofurantoin, which is commonly used as a urinary tract antiseptic, on bladder contractions in male rats. Bladder tissues obtained from male Sprague-Dawley rats were used in the study (n=24). After decapitation, bladder tissues were suspended in an isolated organ bath of 5 ml containing a Krebs-Ringer bicarbonate solution by applying a tension of 1.5 grams. Nitrofurantoin was administered to three groups at doses of 50, 500 and 1000 μM, respectively. The area, peak-to-peak (p-p) and frequency values of bladder contractions were analyzed before and after administration of nitrofurantoin. The data obtained from the analysis were evaluated using the Paired T-Test in the IBM SPSS Statistics Software. Nitrofurantoin was observed to have an inhibitory effect on bladder contractions at all doses. The decrease in the area and peak-to-peak values was statistically significant at all doses (P [Med-Science 2019; 8(1.000): 192-6]

Agomelatine is an antidepressant with a novel mechanism of action. It is a melatonergic agonist for MT1 and MT2 receptors and a serotonin (5-HT2C) receptor antagonist. Agomelatine has been suggested not to have adverse effects on sexual functions. However, the effects of chronic agomelatine administration on reproductive functions have not been sufficiently studied in animal models. We mainly aimed to explore the effects of agomelatine on reproductive functions in the male and female rats. For the experimental studies, Sprague Dawley rats were used. The animals started to receive daily oral agomelatine (10 mg/kg) on post-natal day 21. Agomelatine advanced vaginal opening in the female rats whereas it delayed puberty onset in the male rats. Agomelatine treatment significantly decreased intromission frequencies, which indicates a facilitator role of this antidepressant on male sexual behavior. In the forced swimming test (FST) used for assessing antidepressant efficacy, agomelatine induced a significant decrease in duration of immobility, and an increase in the swimming time, respectively, which confirms the antidepressant-like activity of agomelatine. The present findings suggest that agomelatine shows a strong antidepressant effect in the male rats without any adverse influences on sexual behavior, and its effects on pubertal maturation seem to show sex-dependent differences. (C) 2015 Elsevier B.V. All rights reserved.

We aimed to investigate the effects of nitrofurantoin, a commonly used antibiotic for urinary tract infections, on spontaneous contractions of rat myometrium isolated from 16-day pregnant and nonpregnant rats. Myometrial strips were suspended in a standard organ bath and after the manifestation of spontaneous contractions under 1 g of resting tension, nitrofurantoin was applied to the organ bath as 50, 250 and 500 µM doses. Amplitude and frequency of contractions were recorded for 20 minutes before and after application of the drug. The bath was washed to remove the drug from the medium after recording the effect of each dose and the contractions were enrolled again to show the reversible effect of the drug. The effects of nitrofurantoin on amplitude (milligrams) and frequency of spontaneous contractions were evaluated. Data were statistically analyzed using the Students t test and p [Med-Science 2018; 7(2.000): 315-8]

In this study, we investigated the effect of melatonin on cisplatin-induced spermiotoxicity using quantitative, biochemical and histopathological approaches. Cisplatin (CP, 7 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected. The rats were decapitated on 5th (short-term group) or 50th day (long-term group) after CP injection. Traits of reproductive organs, sperm characteristics, testicular histological findings, and the lipid peroxidation in the testicular tissue were determined. Melatonin mitigated CP-induced reductions in testes, epididymis and accessory gland weights in rats decapitated on day 5. Both short- and long-term CP treatment decreased sperm concentration, sperm motility and increased abnormal sperm rates compared with the control. But the reduction of sperm concentration in long-term CP treatment was insignificant. Although treatment with melatonin provided moderately normalization with respect to sperm concentration in short-term treatment group, melatonin caused a marked normalization of sperm motility in both CP + melatonin groups. Both groups treated with the melatonin showed decreases in abnormal sperm rates compared with alone CP. While testicular malondialdehyde levels were elevated after CP treatment, glutathione peroxidase activity decreased significantly in both groups. Glutathione levels reduced after long-term treatment, but not in short-term group by CP administration. Treatment with CP plus melatonin provided significant amelioration of oxidative stress parameters. Histopathological findings of testes in both short- and long-term treatment groups paralleled the biochemical and spermatogenic results. This study clearly indicates that CP-treatment impaired markedly testicular function and combined treatment with melatonin prevented much of the toxicity in rats.

Objective To investigate a possible protective role of lycopene on adriamycin (ADR)-induced spermiotoxicity using quantitative, biochemical and histopathological approaches. Design Experimental study. Setting Firat University Medical School, Experimental Research Centre, Elazig, Turkey. Animals Twenty four Sprague Dawley rats (8-weeks old) Intervention(s) Adriamycin (10 mg kg−1) was intraperitoneally injected and lycopene (4 mg kg−1) was administered by gavage in corn oil. Main outcome measure(s) Reproductive organ weights were evaluated along with epididymal sperm concentration, motility and morphology. Testicular histological findings, oxidative status and plasma testosterone levels were also determined. Result(s) Lycopene ameliorated ADR-induced reductions in both testes and epididymis weights. ADR decreased sperm motility, increased total abnormal sperm rates, but epididymal sperm concentration was not changed compared to control. A marked normalization was achieved in sperm motility and morphology in pretreatment with lycopene. Although testosterone level was decreased in ADR group compared to control, no changes were observed in pretreatment group. An increase in malondialdehyde and a decrease reduced glutathione concentrations were detected in alone ADR group compared to control. Pretreatment with lycopene restored significantly malondialdehyde and reduced glutathione concentrations. ADR caused severe degenerative changes in germinative cells, atrophy in the diameter size of seminiferous tubules and germinative cell thickness. However, ADR-induced histopathological alterations were effectively reverted by pretreatment with lycopene. Conclusion(s) This study clearly indicates that ADR treatment markedly impaired testicular function and that pretreatment with lycopene might prevent this toxicity.

Background: Oxidative stress is believed to be an important factor in the pathogenesis of acute lung injury (ALI). Aims: The aim of this study was to investigate the possible protective role of alpha-lipoic acid (α-LA) on oleic acid (OA)-induced ALI in rats. Study Design: Animal experiment. Methods: A total of thirty-five rats were divided into five groups in the study. Group 1 served as a control group. Rats in Group 2 (α-LA) were administered α-LA intraperitoneally at a dose of 100 mg/kg body weight (BW). Rats in Group 3 (OA) were administered OA intravenously at a dose of 100 mg/kg BW. In Group 4 (pre-OA-α-LA), α-LA was given 15 minutes prior to OA infusion, and in Group 5 (post-OA-α-LA), α-LA was given two hours after OA infusion. Four hours after the OA infusion, rats were decapitated. Blood samples were collected to measure serum levels of malondialdehyde (MDA) and glutathione (GSH), and the levels of activity for superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Lung tissue samples were taken for histopathological examination. Results: Exposure to OA resulted in increases in serum MDA levels (p

The aim of the present study was to evaluate the preventive role of genistein, a phytoestrogen with a wide variety of pharmacological effects, in an experimental non-alcoholic steatohepatitis (NASH) model.Thirty-six Sprague-Dawley rats were divided into three groups. Group 1 (control) received only a standard rat diet, group 2 (placebo) was given a high fat diet (HFD) plus 0.5 mL/day saline subcutaneously, and group 3 (genistein group) a HFD plus subcutaneous genistein injection at dose of 0.2 mg/kg/day for 6 weeks. All rats were killed after 6 weeks. Serum aminotransferases, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and plasma and liver malondialdehyde (MDA) levels were measured. Additionally, steatosis, ballooning degeneration and inflammation of the liver were examined histopathologically.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P0.001 for each), plasma and liver tissue MDA and plasma TNF-alpha levels (P0.001,0.001,0.01, respectively) were found to be higher in the placebo group than in the control group. TGF-beta levels, however, were comparable in the placebo and control groups (P0.05). Histopathologically, steatosis, inflammatory cells per mm(2) and ballooning degeneration were significantly higher in the placebo group than in the control group (P0.001 for each). Nevertheless, AST and ALT (P0.05 for each), plasma and liver tissue MDA (P0.05 for each) and plasma TNF-alpha levels (P0.001) were significantly decreased in the genistein group compared to the placebo group. Histopathologically, steatosis (P0.05), inflammatory cells per mm(2) and ballooning degeneration (P0.01 for each) in the genistein group were also significantly lower than in the placebo group.Genistein, a strong antioxidant agent, significantly decreased the plasma TNF-alpha level and remarkably prevented the emergence of NASH by improving the biochemical and histopathological abnormalities via attenuating oxidative stress.

The aim of this study was to investigate the possible protective role of antioxidant treatment with ellagic acid on cisplatin-induced nephrotoxicity using biochemical and histopatological approaches. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in the cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The effects of ellagic acid on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GSH peroxidase) and catalase activities and histopatological examinations. Administration of cisplatin to rats induced a marked renal failure, characterized by significant increases in plasma creatinine, urea and calcium concentrations. Cisplatin also induced oxidative stress, as indicated by increased kidney tissue concentrations of malondialdehyde, and reduced activities of GSH peroxidase and catalase. Furthermore, treatment with cisplatin caused a marked tubular necrosis, degeneration and desquamation, luminal cast formation, karyomegaly, tubular dilatation, interstitial mononuclear cell infiltration and inter-tubular haemorrhagia. Ellagic acid markedly reduced elevated plasma creatinine, urea and calcium levels and counteracted the deleterious effects of cisplatin on oxidative stress markers. In the same way, ellagic acid ameliorated cisplatin-induced pathological changes including tubular necrosis, degeneration, karyomegaly, tubular dilatation when compared to the cisplatin alone group. These results indicate that the antioxidant ellagic acid might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat, but not enough to inhibit cisplatin-induced renal dysfunction.