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We investigated how proanthocyanidin treatment altered c-Jun N-terminal kinases, transforming growth factor beta 1, serine/threonine-specific protein kinase, interleukin 1 beta and insulin-like 3 expression in the testis of diabetic rats. We used 24 Wistar albino male rats divided into four groups. Group 1 was untreated control. Group 2 was treated with 40 mg/kg streptozotocin (STZ) for 5 days. Group 3 was treated with 40 mg/kg STZ + 250 mg/kg proanthocyanidin once daily for six weeks. Group 4 was treated with 40 mg/kg STZ + 250 mg/kg proanthocyanidin. Superoxide dismutase activity was reduced in groups 3 and 4 compared to group 2. Glutathione peroxidase activity was increased significantly in groups 3 and 4 compared to groups 1 and 2. Catalase activity was decreased in group 4 compared to group 2. We found that proanthocyanidin increased cell proliferation in diabetic testis. Phospho-JNK and TGF-β1 immunostaining was decreased groups 3 and 4 compared to group 2, while p-Akt immunostaining was increased in groups 3 and 4. The number of IL-1β immunostained cells in groups 3 and 4 was decreased compared to group 2. INSL-3 immunostaining was increased significantly in group 3 compared to group 2. Our findings indicate that proanthocyanidin ameliorated diabetes related testicular dysfunction. Proanthocyanidin contributes to a balanced oxidant-antioxidant status, and balanced proliferation and apoptosis activity in the germinal cells.

Purpose: To investigate the preventive effects of topical sunitinib, sunitinib-hesperetin and sunitinib-doxycycline combinations on corneal neovascularization (CNV), apoptosis and fibrosis in a corneal alkali burn model.Materials and Methods: The corneas of 32 Wistar albino rats were cauterized with silver nitrate to induce CNV. Four groups were created receiving artificial tears (sham), sunitinib (0.5 mg/ml), sunitinib-hesperetin (0.5 mg/ml-0.2 mg/ml), and sunitinib-doxycycline (0.5 mg/ml-20 mg/ml) treatments. Corneal photographs were taken on days 0, 7 and 15. Photographs of the cornea were digitally analyzed to measure the size of the neovascularization area in comparison to the total corneal surface area. On the 15th day, the animals were euthanized, and the eyes were enucleated for immunohistochemical staining to investigate neovascularization, apoptosis, and fibrosis.Results: CNV areas on the 7th day in the sunitinib (4.8%0.07%) and sunitinib-hesperetin (1.1%+/- 0.03%) groups were smaller than those in the sham group (33.9%+/- 0.12%) (p=0.001 and, p

Introduction Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. Objective – methods Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. Results In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls (p p Conclusion We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.

Context: Okra, Abelmoschus esculentus (L.) (Malvaceae), is a medicinal plant widely used in Turkish traditional medicine for the treatment of various diseases such as ulcers and gastritis. Objective: In the present study, we evaluated the gastroprotective effect of okra against ethanol-induced acute gastric mucosal injury in animal models. Materials and methods: Wistar rats were treated with 500, 250 or 100 mg/kg okra; 20 mg/kg famotidine (Fam); and 75 mg/kg quercetin (Que). Following a 60 min period, all the rats were given 1 mL of ethanol (80%). One hour after the administration of ethanol, all groups were sacrificed. Results: At 5000 mg/kg, the extract produced (okra) no signs of toxicity in animals. Okra 500, 250, 100, Fam 20 and Que 75 inhibited ulcer formation by 81.0, 67.5, 67.0, 76.3 and 72.4%, respectively. Okra 500 significantly decreased edema, hemorrhage and inflammation scores compared with the ethanol group (p < 0.05). The oxidant levels decreased significantly in the all study groups compared within ethanol group (p < 0.001). Serum beta-carotene and retinol levels significantly increased 40.2 and 45.4% in the okra 500 group. In okra 500, 250 and Fam 20 groups, apoptosis significantly decreased (p < 0.001), while okra 500, 250 and Fam 20 groups showed a higher percentage of cell proliferation compared with the ethanol group (p < 0.001). Discussion and conclusions: Our in vivo data indicate that okra has a gastroprotective effect against ethanol and could reduce the gastric ulcer as seen from biochemical and histopathological results. We suggest that okra could be a possible therapeutic antiulcer agent. Yildiz Technical University research fund [2015-07-04-KAP02] This study was supported by grants from the Yildiz Technical University research fund [2015-07-04-KAP02].

It is becoming progressively more understandable that overdose of paracetamol in both humans and animals causes severe hepatotoxicity. Apomorphine is known as a neuroprotective agent. Due to the protective effect, apomorphine had been tested in experimental studies on different models. Findings obtained through series of expriments suggested that apomorphine may also be useful in liver toxicity. The aim of this study is to investigate the relationship among the hepatoprotective mechanism of apomorphine and to determine the possible role of apomorphine on paracetamol-induced hepatotoxicity in rats. 30 Sprague Dawley rats (adult male) were distributed into 5 groups. Group 1 was the control group and did not receive any medication. Group 2 received only paracetamol 2 g/kg by intragastric gavage to induce hepatotoxicity. Groups 3 and 4 were given apomorphine 1 mg/kg and 2 mg/kg by intraperitoneal injection, respectively. Groups 3 and 4 were given 2g/kg of Paracetamol. In Group 5, rats were treated with 2 mg/kg of apomorphine. Drug-treated rats were given food for the next 24 h until they were sacrified. Moreover, we also performed AST, ALT measurements in serum, MDA and SOD levels in liver tissues and histopathological analysis of the liver in all groups. Apomorphine had positive effects on both liver enzymes, oxidative stress markers and histopathological results in paracetamol-induced hepatotoxicity. Additionally, apomorphine at 2 mg/kg dose was significantly more protective as compared to 1 mg/kg as evidenced by the histopathological examination results. It was thought that apomorphine was found hepatoprotective on paracetamol-induced hepatotoxicity, especially at higher doses such as 2 mg/kg.

Objectives The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine-induced chronic kidney disease (CKD) model. Methods Rats were orally given, for 28 consecutive days, either adenine alone or together with either aqueous extract of H. sabdariffa calyces (5 and 10%) or anthocyanins (50, 100 and 200 mg/kg of anthocyanin concentrate). For comparative purposes, two groups of rats were given lisinopril (10 mg/kg). Key findings When either H. sabdariffa aqueous extract or the anthocyanins isolated from it was administered along with adenine, the adverse effects of adenine-induced CKD were significantly lessened, mostly in a dose-dependent manner. The positive effects were similar to those obtained by administration of lisinopril. Conclusions The results obtained show that both H. sabdariffa and its anthocyanins could be considered as possible promising safe dietary agents that could be used to attenuate the progression of human CKD. This could have added significance as H. sabdariffa tea is widely consumed in many parts of Africa and Asia and is thus readily available.

Contrast induced nephropathy (CIN) is a major cause of morbidity, and increased costs as well as an increased risk of death. This study was evaluated effects of exogenous sphingosylphosphorylcholine (SPC) administration on CIN in rats. Eight animals were included in each of the following eight groups: control, control phosphate-buffered solution (PBS), control SPC 2, control SPC 10, CIN, CIN PBS, CIN SPC 2 and CIN SPC 10. The induced nephropathy was created by injected with 4 g iodine/kg body weight. SPC was administered 3 d at a daily two different doses of 2 μm/mL and 10 μm/mL intraperitoneally. The severity of renal injury score was determined by the histological and immunohistochemical changes in the kidney. Malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) were determined to evaluate the oxidative status in the renal tissue. Treatment with 2 and 10 μM SPC inhibited the increase in renal MDA, NO levels significantly and also attenuated the depletion of SOD in the renal injuryCIN. These data were supported by histopathological findings. The inducible nitric oxide synthase positive cells and apoptotic cells in the renal tissue were observed to be reduced with the 2 and 10 μM SPC treatment. These findings suggested that 2 and 10 μM doses can attenuate renal damage in contrast nephropathy by prevention of oxidative stress and apoptosis. The low and high dose SPC may be a promising new therapeutic agent for CIN.

Objectives We aimed to investigate the effects of hesperetin as a flavanon both histopathologically and immunohistochemically on cochlear apoptosis in a rat model of cisplatin-induced ototoxicity (CIO). The evaluation of the effects of hesperetin on cisplatin-induced hearing loss was performed using distortion product otoacoustic emission (DPOAE). Methods Twenty-eight wistar albino rats were used in the current study. The rats were randomly divided into four groups with seven rats in each group. Group C was exposed to a single dose of cisplatin (12 mg/kg) by intraperitoneal injection. Group CH received intraperitoneally cisplatin (12 mg/kg) and hesperetin (20 mg/kg). Group H was exposed to hesperetin (20 mg/kg) intraperitoneally. The sham group (group S) received normal saline (6 cc) intraperitoneally. The measurements of DPOAE and signal-noise ratios (SNR) were performed before the treatment and again on the first and 6 days after administration of the drugs. Rats were sacrificed and cochleae were dissected 10 days after drug administration. The cochlear tissue was assessed in all groups by histopathologic, immunohistochemical and TUNEL assay. In addition, serum oxidative stress markers and antioxidant parameters were analyzed. Results There was a significant difference between the basal value and the sixth day at frequencies 8.4, 9.6 and 9.96 for group C. We also found a significant difference between the first and sixth day at frequencies 7.2, 8.4, 9.6 and 9.96. On the 6th day, there were significant differences between C and S groups at all frequencies except 2.4. We showed a significant difference between C and H groups at frequencies 4.8, 6.0, 8.4, 9.6 and 9.96. There was also a significant difference between C and CH groups at frequencies 2.4, and 3.6. We found lower levels of oxidants and higher levels of antioxidants in CH group as compared to C group. C group had a significantly greater number of TUNEL-positive cells than did S, H and CH groups. The number of TUNEL-positive cells in CH group was higher than in S and H groups. There was a significant difference between the positive PCNA cells of CH group compared to S and H groups in spiral ganglion and stria vascularis. In addition, there were no positive PCNA cells in C group. Conclusions Hesperetin may prevent ototoxicity by increased antioxidant enzymes and reduced oxidant parameters and protected against apoptosis resulting from a proliferation of cochlear cells in CIO.

To investigate the antiapoptotic effect of topically administered azithromycin (AZM) on corneal epithelial and endothelial cells in a rat model of corneal alkali burn.Twenty-four Wistar albino rats were divided into 4 equal groups as pseudovehicle (group 1), control (group 2), alkali burned (group 3), and treatment (group 4) groups. Alkali injury was induced only in the right corneas of rats belonging to groups 3 and 4 using 1N NaOH. The rats in group 3 and the rats in group 4 were respectively treated either with an artificial tear gel or with 1.5% AZM eye drops for 5 days. At the fifth day of the experiment, the apoptosis in the corneal epithelium and endothelium of all rats was assessed using a terminal dUTP nick-end labeling (TUNEL) assay. In addition, tumor necrosis factor-alpha (TNF-α) density in the corneal epithelium was measured in all rats.The mean numbers of TUNEL+ cells in the corneal epithelium and endothelium of rats in group 3 were 117.1 ± 23.8 and 34.6.± 11.3, respectively, whereas in group 4, they were 75.8 ± 15.7 and 14.7 ± 3.5, respectively. Also the mean TNF-α densities in the corneal epithelium in group 3 and group 4 were 2.65 ± 1.3 and 1.65 ± 1.1, respectively. There was a significant decrease in the mean number of TUNEL+ cells in the corneal epithelium and endothelium and in the mean TNF-α density in the corneal epithelium of rats in group 4, when compared with group 3.Topically applied AZM can decrease TNF-α-induced apoptosis in corneal alkali burn.

Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air pollution aggravates chronic renal failure.

Karaca, Turan (Trakya author) The erectile dysfunction drug sildenafil has cardiopulmonary protective actions, and a nephroprotective action in cisplatin and ischemia-reperfusion- induced acute kidney injury. Here, we assessed its possible ameliorative action in a model of chronic kidney disease (CKD) using adenine feeding. Eight groups of rats were treated with saline (controls), adenine (0.25% w/w in feed daily for 5 weeks), and oral sildenafil (0.1, 0.5 or 2.5 mg/kg), either alone, or concomitantly with adenine. Urine was collected 24 h after the end of the treatments from all rats and blood pressure measured, followed by collection of blood and kidneys for the measurement of several functional, biochemical and histopathological parameters. Adenine treatment reduced body weight, creatinine renal clearance, and increased water intake and urine output, as well as the plasma concentrations of urea and creatinine, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase activity, and albumin in urine. Adenine also increased the concentrations of the uremic toxins indoxyl sulfate, uric acid and phosphate, and a number of proteins and inflammatory cytokines, and decreased that of several anti - oxidant indices. Renal histopathological markers of damage (inflammation and fibrosis) were significantly increased by adenine. Sildenafil, given simultaneously with adenine, induced a dose - dependent improvements in most of the above parameters, suggesting its possible use as adjunct treatment for CKD in humans.

To examine the effects of royal jelly (RJ) on testicular damage in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Eighteen adult Wistar albino rats were used, 6 in each of the 3 treatment groups: Group A: control, Group B: STZ-induced diabetes (untreated), Group C: STZ-induced diabetes plus RJ (400 mg/kg daily for 4 weeks). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Four weeks after the onset of diabetes, testicular apoptotic cell death was examined using immunohistochemical staining for caspase-3 and Ki67 staining for localization of proliferative cells. Results: Compared with the control, the body and testicular weights of the RJ-treated and untreated diabetic rats were decreased (P < 0.05). The histopathological examination showed a significant increase in degenerative changes in the seminiferous tubules and in spermatogenesis of the STZ-treated rats. In contrast, the RJ treatment group showed near-normal morphology, in addition to an increased intensity of immunohistochemical staining for Ki67-positive cells. Conclusion: Diabetes induced a significant increase in testicular apoptotic cell death (caspase-3-positive cells). Caspase-3-positive cells were significantly decreased in the STZ plus RJ-treated group compared with the untreated STZ-induced diabetic group (P < 0.05).

It is well-established that there is a crosstalk between the lung and the kidney, and several studies have reported association between chronic kidney disease (CKD) and pulmonary pathophysiological changes. Experimentally, CKD can be caused in mice by dietary intake of adenine. Nevertheless, the consequence of such intervention on the lung received only scant attention. Here, we assessed the pulmonary effects of adenine (0.2% w/w in feed for 4 weeks)-induced CKD in mice by assessing various physiological histological and biochemical endpoints. Adenine treatment induced a significant increase in urine output, urea and creatinine concentrations, and it decreased the body weight and creatinine clearance. It also increased proteinuria and the urinary levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Compared with control group, the histopathological evaluation of lungs from adenine-treated mice showed polymorphonuclear leukocytes infiltration in alveolar and bronchial walls, injury, and fibrosis. Moreover, adenine caused a significant increase in lung lipid peroxidation and reactive oxygen species and decreased the antioxidant catalase. Adenine also induced DNA damage assessed by COMET assay. Similarly, adenine caused apoptosis in the lung characterized by a significant increase of cleaved caspase-3. Moreover, adenine induced a significant increase in the expression of nuclear factor erythroid 2–related factor 2 (Nrf2) in the lung. We conclude that administration of adenine in mice induced CKD is accompanied by lung oxidative stress, DNA damage, apoptosis, and Nrf2 expression and fibrosis.

Potassium bromate (KBrO3) is used in many countries in cosmetic and food industries. In this work, we investigated in male Sprague-Dawley rats, the effect of four graded oral doses of KBrO3 (5, 15, 45 and 135 mg/kg/day for 28 days) on renal function tests, inflammation, oxidative damage, and apoptosis, as well as on histopathology, using several traditional and novel renal injury biomarkers in plasma, urine and renal tissues. We also tested the possible ameliorative action of the renoprotective prebiotic agent gum acacia (GA) on the actions of KBrO3 when given concomitantly with it in the drinking water at a concentration of 15%w/v. Taken together, the results indicated that treatment with KBrO3 at the 45 and 135 mg/kg doses caused a significant dose-dependent nephrotoxicity, as evident by the measured renal structural and functional indices and biomarkers of toxicity. GA co-treatment significantly abated most of the indices and biomarkers of the renal toxicity caused by KBrO3, suggesting a beneficial effect and its possible inclusion in edible products where KBrO3 is still used.

This study aimed at investigating the possible ameliorative effects of sitagliptin in mice with gentamicin (GEN) nephrotoxicity. Sitagliptin was given to the animals at an oral dose of 10mgkg-1 per day for 10days, and in some of these mice, GEN was injected intraperitoneally at a dose of 100mgkg-1 per day during the last seven days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring several indices in plasma, urine and renal cortex homogenates. GEN treatment induced nephrotoxicity as evidenced by significantly (P

Background: The present study evaluated, in different oestrus cycle phases, the oestrogen receptor alpha (ERα) and progesterone receptor (PgR) in rates with hyperthyroid ovaries and uterus.Materials and Methods: Sixty-four adult female wistar albino rats were used. Animals were randomly separated into eight different groups, four of which constituted the control group and the other four of which were the actual experimental group. Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 250 µg/kg) for 21 days.Results: Hyperthyroidism induced decreased plasma TSH levels and increased plasma free T4 levels (P < 0.001). In addition, it increased plasma oestrogen levels in all cycle phases, and plasma progesterone levels increased in different cycle phases, excluding the oestrus phase, in rats (P < 0.01). By the end of the experiment, ERα percentages were decreased in oestrus days in uterine luminal epithelium; however, ERα percentages were increased in metoestrus phases in hyperthyroid rats. ERα was elevated in proestrus, metoestrus and dioestrus phases in the corpus luteum, and hyperthyroidism also increased ERα percentages in theca folliculi. In uterine luminal epithelium, the hyperthyroidism group showed higher expressions of PgR (P < 0.05) in oestrus and metoestrus phases and decreased oestrus phase compared to control rats.Conclusions: As a result, we conclude that both the levels of plasma estrogen and progesterone as well as the differences in the distributions of relevant receptors in ovarian and uterus tissues have an impact on female infertility due to hyperthyroidism. DOI: http://dx.doi.org/10.3126/ajms.v6i4.11816 Asian Journal of Medical Sciences Vol.6(4) 2015 14-20

Objective To investigate the effect of desferrioxamine (DFX) on ipsilateral and contralateral testis damage caused by experimental testis torsion and detorsion. Materials and methods Forty rats were divided into five groups (n = 8): control, torsion (T), torsion + desferrioxamine (T + DFX), torsion/detorsion (T/D), and torsion/detorsion + desferrioxamine (T/D + DFX). The right testes of the rats were subjected to torsion and detorsion for 3 h each. Thirty minutes before the application of torsion and detorsion, DFX (100 mg/kg) was administered intramuscularly. Blood samples and testicular tissues were examined using specific biochemical and histopathological methods. Results Ipsilateral and contralateral testis tissue glutathione levels in the T group decreased compared with the control and T + DFX groups. Plasma glutathione peroxidase activity in the T, T/D, and T/D + DFX groups was lower than in the control group. Plasma catalase activity in the T and T/D groups decreased compared with the control group. Ipsilateral mean seminiferous tubule diameter of the T group was lower than that of the T + DFX group. The ipsilateral mean testis biopsy scores in the T and T/D groups were lower than in the control group. Conclusion The administration of DFX prior to torsion may be useful only for preventing ischemic damage in ipsilateral and contralateral testes.

Hesperidin (HES), a citrus fruit extract, has beneficial effects on various ischemia/reperfusion (I/R) models. We aimed to evaluate the possible positive effects of hesperetin (HPT), an active metabolite of HES, on a rat ovarian I/R model. We divided 24 Wistar Albino rats into four groups. Group I (n = 6) was sham operated, Group II (n = 6) was the I/R group, Group III (n = 6) was the I/R + solvent group and Group IV (n = 6) was the I/R + HPT group. Three hours of ischemia and 3 h of reperfusion were performed on each rat in Groups II, III, and IV. Dimethyl sulfoxide (DMSO) was given intraperitoneally to the rats in the III. Group, and 50 mg/kg of HPT dissolved in DMSO was given intraperitoneally to the rats in the IV. Group 30 min before reperfusion. After 3 h of reperfusion, the ipsilateral ovaries of the rats were examined immunohistochemically to detect apoptosis. Hematoxylin and eosin (H and E) staining demonstrated less edema and hemorrhage in the group where HPT was applied. Caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining showed significantly lower apoptosis in the group where HPT was used when compared to either the I/R or solvent group. To the best of our knowledge, this is the first study that shows the beneficial effects of HPT in an ovarian I/R injury. HPT improved tissue damage and apoptosis caused by I/R injury. To identify the possible positive effects of HPT in ovarian torsion of humans and use in clinical practice, more studies must be performed.

Dexmedetomidine is an alpha 2 adrenoceptor agonist and can be used for postoperative sedation, analgesia and anesthesia-sparing properties. Furthermore, the neuroprotective effects against ischemia/reperfusion (I/R) injury in the central nervous system have been shown in experimental studies. This study aimed to investigate the protective effects of dexmedetomidine against apoptosis in retinal I/R injury in the rat.Retinal I/R injury was induced by transient elevation of intraocular pressure. Eighteen animals were divided into three groups (n = 6): sham, I/R and treatment. The I/R injury and protective effects of the dexmedetomidine were evaluated by retinal thickness determined by histological sections, terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) and immunohistochemistry of caspases 3.A decrease in the retinal thickness and an increase in the apoptotic cells were found to be statistically significant in I/R and treatment groups when compared with the control group. However, in comparison with the I/R group we realized that the administration of dexmedetomidine reduced the thinning of retinal thickness and also decreased the number of caspases 3 and TUNEL-positive cells.Dexmedetomidine is protective against apoptosis in retinal I/R injury in rats.

There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine–protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor α and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use of WPS use all over the world, especially in young adults.

The distribution of Mast Cells (MCs) was studied in the lymphoid organs of 7, 14, 21 and 30 days old quails (Coturnix coturnix Japonica) kept in different photoperiods using light microscopy histochemical techniques. The distribution of MCs was determined in different age groups housed in continuous light (23L:1D) or in a light-dark regimen (18L: 61)). Tissue samples were obtained under deep anesthesia from birds in the four age groups, fixed in Mota's fixative (basic lead acetate) for 24 h and embedded in paraffin. Six micrometre-thick sections were stained with 0.5% toluidine blue and the number of MCs counted under the microscope. The numbers of MCs were significantly different between both age and light treatment groups. The number of mast cells was significantly lower (p

The present studies were designed to evaluate supplemental grape seed extract (GSE) and vitamin E supplements on lipid peroxidation, on antioxidant systems and peripheral blood lymphocytes in rats exposed to x-rays. Three groups of rats were investigated: a control group (CG) received intraperitoneal (i.p.) physiological serum 1 mL/day (n=10), i.p.; a vitamin E group (VG) received 50 mg/kg/day (n=10); an i.p. grape seed extract group received 50 mg/kg/day (n=10). Four weeks later, a 6 Gy radiation dose was given to the rats. Blood samples were taken 24 h later after irradiation and lymphocyte, malondialdehyde (MDA), reduced glutathione (GSH), nitrate, nitrite, reduced ascorbic acid, retinol, beta-carotene and ceruloplasmin concentrations were analysed. The levels of GSH (p

Summary Background and objective Ulcerative colitis is an inflammatory condition of the colon in the gastrointestinal system. Currently, the most potent medications used for ulcerative colitis produce no response in 20–30% of cases. There is a need for more efficient and reliable medications. Tyrosine kinase inhibitors have shown efficacy in some inflammatory diseases. Although dasatinib, a tyrosine kinase inhibitor, suppresses proinflammatory cytokines in colonic tissue, there are a few cases of hemorrhagic colitis with dasatinib. There is no study investigating the effect of dasatinib on experimental colitis. We aimed to investigate the effect of dasatinib in a colitis model induced with acetic acid in our study. Methods In the study, 24 male Sprague-Dawley rats randomly distributed into 4 groups of 6 rats each as control, dasatinib, colitis and dasatinib + colitis groups. For colitis induction, 4% acetic acid was used. Sacrificing of the rats was performed on the seventh day. Disease activity, morphologic and histological injury, superoxide dismutase, myeloperoxidase and malondialdehyde activity, TNFα and CD3 expression were assessed in colonic tissue. Results Apart from malondialdehyde, significant difference in all parameters between the control and colitis groups was determined. Difference between the colitis and colitis + dasatinib groups was not significant in only weight loss and biochemical parameters. Though dasatinib does not fully resolve the changes in colitis, there was significant regression. Conclusions Dasatinib decreased the inflammation in a rodent model of colitis. It may be provide this effect by the suppression of TNFα. Dasatinib may be one of the treatment options for ulcerative colitis.

This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis.Â

Background/aim: To investigate the efficacy of diffusion-weighted magnetic resonance imaging (DWI) in the diagnosis and staging of fibrosis induced by experimental bile duct ligation (BDL). Materials and methods: Twenty-four rats were divided randomly into four groups: control, BDL - 3 days, BDL - 2 weeks, and BDL - 4 weeks. DWI was performed with b-values of 100 and 500 on the rats from control group at day zero, on the rats from the BDL - 3 days group at the end of day 3, on the rats from the BDL - 2 weeks group at the end of day 14, and on the rats from the BDL - 4 weeks at the end of day 28. Results: When fibrosis scores generated in all groups were evaluated together, a strong negative correlation was detected between fibrosis scores and apparent diffusion coefficient (ADC) values measured using b 100 and b 500. ADC values obtained using b 100 were found to be significantly higher compared to the fibrosis observed in both the BDL - 2 weeks and BDL - 4 weeks groups (P < 0.003 and P < 0.001, respectively). Conclusion: We think that DWI may be an alternative to liver biopsy for the diagnosis and staging of hepatic fibrosis with underlying extrahepatic cholestasis.

Purpose: This study aimed to investigate the effect of quercetin on apoptotic cell death induced by ischemia-reperfusion (I/R) injury in the rat retina. Methods: Twenty-four rats were divided into four equal groups: control, ischemic, solvent, and quercetin. I/R injury was achieved by elevating the intraocular pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of quercetin and dimethyl sulfoxide (DMSO) were performed in the quercetin and solvent groups, respectively, immediately prior to I/R injury, and the researchers allowed for the retinas to be reperfused. Forty-eight hours after injury, the thicknesses of the retinal ganglion cell layer (RGCL), inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were measured in all groups. Moreover, the numbers of terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+)] cells and caspase-3 (+) cells in both INL and ONL were evaluated in all groups. Results: The administration of quercetin was found to reduce the thinning of all retinal layers. The mean thickness of INL in the quercetin and ischemic groups was 21 ± 5.6 µm and 16 ± 6.4 µm, respectively (P

Akşit, Hasan (Balikesir Author), Background and aims: Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal system. In some cases, current medications used for inflammatory bowel disease may not be enough for remission, creating a need for more potent and reliable medications. There is no study showing the efficacy of fostamatinib, with proven effects on some inflammatory diseases, on ulcerative colitis. In our study we planned to research the efficacy of fostamatinib, a spleen tyrosine kinase inhibitor, on acetic acid-induced colitis. Methods: The study included 28 male Sprague-Dawley rats, randomly divided into control group, fostamatinib group, colitis group and fostamatinib + colitis group, each containing seven rats. Colitis induction was performed with 4% acetic acid. Colonic inflammation was assessed with disease activity index, macroscopic and histological damage scores, colonic myeloperoxidase, malondialdehyde and superoxide dismutase activity, and tumour necrosis factor alpha [TNF alpha], CD3, Syk, and phospho-Syk expression. Results: There was a significant difference between the colitis and control groups in terms of all parameters. The disease activity index, macroscopic and microscopic damage scores, immunohistochemical TNF alpha, CD3, Syk, and phospho-Syk expression, and tissue myeloperoxidase activity were found to be significantly lower in the colitis + fostamatinib group compared with the colitis group. There was no significant difference between the two groups in terms of myeloperoxidase and malondialdehyde activity. Conclusions: Fostamatinib reduced the inflammatory damage in the experimental colitis. This effect may be due to suppression of TNF alpha, T-lymphocytes, and neutrophils in colonic mucosa via suppression of Syk. Fostamatinib may be an appropriate treatment alternative for ulcerative colitis. Further clinical studies are required to support this.

T. Karaca, Cemek M., Kanter M.: Lipid Peroxidation and Antioxidant Levels, and Alpha Naphthyl Acetate Esterase Activity of Peripheral Blood Lymphocytes in Mallard, Muscovy and Pekin Ducks. Acta Vet. Brno 2006, 75: 33-38. The aim of this study was to determine blood levels of malondialdehyde (MDA), reduced glutathione (GSH), ceruloplasmin and vitamin C, and the percentages of peripheral blood Tlymphocytes using the alpha-naphthyl acetate esterase (ANAE) method on Mallard (Anas platyrhynchos), Muscovy (Cairina moschata) and Pekin (Anas domestica) ducks. Blood samples were obtained from 8 adult ducks of each breed. The serum levels observed in Mallard, Muscovy and Pekin ducks respectively were 0.8, 1.07 and 1.3 nmol MDA per ml; 77.4, 66.9 and 78.7 mg GSH per 100 ml; 23.9, 26.1 and 24.1 mg ceruloplasmin per 100 ml; and 0.50, 0.52 and 0.70 mg vitamin C per 100 ml. The percentage of the ANAE (+) lymphocytes was 57.9%, 54.8% and 55.1% in Mallard, Muscovy and Pekin ducks, respectively. In this study, blood levels of lipid peroxidation and nonenzymatic antioxidants in the Mallard, Muscovy and Pekin ducks were determined. Lipid peroxidation, antioxidant, alpha-naphthyl acetate esterase, T-lymphocyte, duck

The pathogenesis of fibrosis in scleroderma (SSc) is unknown. TGF-β and platelet-derived growth factor are important in the development of fibrosis and tyrosine kinases are involved in these pathways. The possible antifibrotic effects of various kinase inhibitors in SSc have been studied before. Spleen tyro-sine kinase (Syk) is a protein tyrosine kinase which activates intracellular signal transduction pathways; and has been claimed to be involved in the pathogenesis of systemic autoimmune diseases. Inhibition of Syk suppresses IgE- and IgG-associated FcR signal activation in various cell types; and suppresses experimental arthritis and skin and kidney disease in lupus-prone mice. We investigated the ability of a small drug, the Syk inhibitor, fostamatinib, to protect mice from bleomycin-induced SSc.Four study groups of BALB/c mice were included into this study: control, bleomycin (administered subcutaneously to BALB/c mice for 21 days), bleomycin and fostamatinib (mice fed with chow containing a Syk inhibitor for 21 days), and fostamatinib alone groups. Skin and lung tissue specimens were obtained and evaluated histologically.Treatment with fostamatinib significantly reduced skin thickness and fibrosis. Mice treated with fostamatinib also displayed less fibrosis and inflammation in the lung tissue. Following fostamatinib treatment, Syk, phospho-Syk, and TGF-β expression decreased in both skin and lung tissues.The Syk inhibitor fostamatinib prevented bleomycin-induced fibrosis and inflammation in the skin and in the lung. The anti-fibrotic effect of fostamatinib is linked to reduced Syk phosphorylation and TGF-β expression. The Syk pathway appears as a potential molecular target for therapeutic intervention in SSc.

Objective: To investigate the protective effect of quercetin (QE), an anti-inflammatory and anti-oxidant agent, on torsion–detorsion induced histopathological changes and blood IMA levels in experimental ovarian ischemia-reperfusion (IR) injury. Study design: Twenty-four female Wistar rats were randomly divided into four groups in this study (n = 6). Group I, (sham operation); Group II, torsion–detorsion plus saline (IR); Group III, torsion– detorsion plus solvent (dimethylsulfoxide: DMSO, IR + DMSO); Group IV, torsion–detorsion plus 15 mg/ kg/bw quercetin (IR + QE) injected intraperitoneally 30 min prior to detorsion. After 3 h of reperfusion, the right ovaries were removed surgically. The ovary tissue samples were fixed in 10% formalin solution for histopathological and immunohistochemical examination. Blood samples were obtained at the end of the procedures for each group of animals. Results: Ovarian sections in Groups II and III showed higher follicular cell degeneration, hemorrhage, vascular congestion and edema when compared with Group I. Administration of quercetin in rats significantly prevented degenerative changes in the ovary. Significantly less histopathological changes were found in Group IV compared with Groups II and III. Caspase-3 and TUNEL positive cells were detected in the ovarian surface, follicle epithelium, and stromal cells in all experimental groups, and there was a significant increase in Groups II and III compared with Group I (P < 0.05). Treatment with quercetin decreased the number of caspase-3 and TUNEL positive cells. IR increased the ischemia modified albumin (IMA) levels in comparison to the sham group (1.06 0.10 ABSU and 0.92 0.08 ABSU, P < 0.05). Quercetin administration before IR reduced the levels of IMA (0.93 0.08 ABSU, P < 0.05). Conclusion: Administration of quercetin is effective in preventing tissue damage induced by IR injury in ovaries.

Background/purpose The goal of this study was to evaluate effects of exogenous sphingosylphosphorylcholine (SPC) administration on acute lung injury induced by pulmonary contusion in rats. Methods Eight animals were included in each of the following five groups: control, contusion, contusion phosphate-buffered solution (PBS), contusion SPC 2, contusion SPC 10. SPC was administered 3days at a daily two different doses of 2μm/ml and 10μm/ml intraperitoneally. The severity of lung injury was determined by the neutrophil activation and histological and immunohistochemical changes in the lung. Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) were determined to evaluate the oxidative status in the lung tissue. Results Treatment with 2μM SPC inhibited the increase in lung MDA and NO levels significantly and also attenuated the depletion of SOD, GPx, and GSH in the lung injury induced by pulmonary contusion. These data were supported by histopathological findings. The inducible nitric oxide synthase (iNOS) positive cells and apoptotic cells in the lung tissue were observed to be reduced with the 2μM SPC treatment. But, the 10μM SPC treatment did not provide similar effects. Conclusions In conclusion, these findings suggested that 2μM SPC can attenuate lung damage in pulmonary contusion by prevention of oxidative stress, inflammatory process and apoptosis. All these findings suggest that low dose SPC may be a promising new therapeutic agent for acute lung injury.

Şimşek, Nejdet (Balikesir Author), The regional distribution, relative frequency, and appearance of glucagon (A-cell)-, insulin (B-cell)-, somatostatin (D-cell)-, gastrin (G-cell)-, and serotonin (EC-cell)-secreting cells in the endocrine and exocrine pancreas of Van cats were examined using the immunohistochemistry method. Glucagon immunopositive A-cells were principally found in the central region of the islets of Langerhans, while insulin immunopositive B-cells were located in the periphery of the pancreatic islets. Moreover, several A- and B-cells were observed as only single cells or clusters of 2 to 3 immunopositive cells in the exocrine parenchyma and the pancreatic duct epithelium. Somatostatin and gastrin immunopositive reactivities were negligible in the peripheral regions of the pancreatic islets of Langerhans and in the exocrine parenchyma. However, serotonin-immunopositive EC-cells were observed in neither the endocrine islets nor any other sites of the tissue. The existence, regional distribution, and relative frequency of A-, B-, D-, G- and EC-cells in the pancreas of Van cats have been analyzed in this study for the first time. The immunopositivity and distribution of endocrine cells in the Van cat pancreas were determined to be partially different from those of other carnivorous species such as dogs and other cats.

Purpose. Hesperetin and naringenin are naturally common flavonoids reported to have antioxidative effects. This study was performed to investigate whether either hesperetin or naringenin has a protective effect against apoptosis on retinal ischemia/reperfusion (I/R) injury.Methods. Retinal I/R was induced by increasing the intraocular pressure to 150 mmHg for 60 minutes. Thirty-three male Wistar albino rats were randomised into 5 groups named control, I/R + sham, I/R + solvent (DMSO), I/R + hesperetin, and I/R + naringenin. Animals were given either hesperetin, naringenin, or the solvent intraperitoneally immediately following reperfusion. Thickness of retinal layers and retinal cell apoptosis were detected by histological analysis, tunel assay, and immunohistochemistry assay.Results. Hesperetin and naringenin attenuated the I/R-induced apoptosis of retinal cells in the inner and outer nuclear cells of the rat retina. Retinal layer thickness of the naringenin treatment group was significantly thicker than that of the hesperetin, sham, and solvent groups (P<0.05).Conclusions. Hesperetin and naringenin can prevent harmful effects induced by I/R injury in the rat retina by inhibiting apoptosis of retinal cells, which suggests that those flavanones have a therapeutic potential for the protection of ocular ischemic diseases.

AIM: The objective of the present study was to evaluate the effects of green tea extract and Lactobacillus casei strain Shirota on levels of serum minerals (Ca, Cu, Zn, Fe, Mg and Mn), cholesterol, triglyceride, glucose and lactate in rats on high carbohydrate and lipid diets. METHODS: Thirty fi ve healthy Wistar albino rats were used, fi ve in each of seven experimental groups: control (group A), high-carbohydrate diet (group B), high-carbohydrate diet supplemented with probiotic bacteria for 8 weeks - Lactobacillus casei strain Shirota (group C), high-carbohydrate diet supplemented with green tea extract for 8 weeks - in drinking water: 100 mg/kg/day (group D), high-lipid diet for 8 weeks (group E), high-lipid diet supplemented with probiotic bacteria for 8 weeks (group F), high-lipid diet supplemented with green tea extract for 8 weeks- in drinking water: 100 mg/kg/day (group G). RESULTS: A signifi cant increase (p< 0.05) in serum cholesterol was observed in groups treated with high-lipid, and high-lipid + green tea extracts (E and G) compared with other groups (P< 0.05). Serum triglyceride levels were signifi cantly lower in the high-carbohydrate + probiotic group (C) than in other groups (p< 0.05). High-calorie diet, green tea extract and probiotic bacteria had no infl uence on serum lactate levels in any of the groups. Serum Ca levels decreased signifi cantly only in the high-carbohydrate diet group (p< 0.05). However, serum Zn and Fe concentrations increased signifi cantly in the high-lipid and high-lipid plus probiotic bacteria groups, respectively (p< 0.05 and 0.01). Serum Mg levels were signifi cantly lower in all experimental groups compared to the control group (P< 0.01). L. casei strain Shirota and the green tea extract, signifi cantly lowered serum glucose levels in the highcarbohydrate groups compared to high-lipid groups (p< 0.05). CONCLUSION: The green tea extract and L. casei strain Shirota decreases serum glucose and triglyceride levels in rats fed on high-calorie diets., AMAÇ: Bu çalıșmanın amacı, yeșil çay ekstraktı ve Lactobacillus casei strain Shirota’nın yüksek karbonhidrat ve lipit içerikli diyetle beslenen ratlarda serum mineralleri (Ca, Cu, Zn, Fe, Mg and Mn), kolesterol, trigliserid, glikoz ve laktat düzeyleri üzerine etkilerinin araștırılmasıdır. YÖNTEM: Otuzbeș sağlıklı Wistar albino rat her grupta 5 hayvan olacak șekilde 7 gruba ayrıldı: Kontrol grubu (A), yüksek-karbonhidratlı diyet grubu (B), yüksek karbonhidratlı diyet ve 8 hafta süreyle probiyotik bakteri ilaveli grup- Lactobacillus casei strain Shirota (C), yüksek karbonhidratlı diyet ve 8 hafta süreyle yeșil çay ekstraktı verilen grup (D), yüksek lipit içerikli diyet grubu (E), yüksek lipit içerikli diyet ve 8 hafta süreyle probiyotik bakteri ilaveli grup- Lactobacillus casei strain Shirota (F) ve yüksek lipit içerikli diyet ve 8 hafta süreyle yeșil çay ekstraktı ilaveli grup (G). BULGULAR: Serum kolesterol seviyesinin yüksek lipit ve yüksek lipit + yeșil çay ekstraktı ilaveli gruplarda (grup E ve G) kontrole ve diğer deneme gruplarına göre anlamlı olarak artığı tespit edildi (p< 0.05). Serum trigliserid seviyesi yüksek karbonhidrat + probiyotik ilaveli grupta (grup C) diğer deneme gruplarından anlamlı olarak düșüktü (p< 0.05). Yüksek kalorili diyet, yeșil çay ekstraktı ve probiyotik ilavesinin gruplarda serum laktat seviyesi üzerine herhangi bir etkisinin olmadığı görüldü. Serum Ca düzeyinin yanlızca yüksek karbonhidrat içerikli diyet grubunda anlamlı olarak azaldığı tespit edildi (p< 0.05). Bununla birlikte, serum Zn ve Fe konsantrasyonları- nın yüksek lipit ve yüksek lipit + probiyotik ilaveli gruplarda sırasıyla p< 0.05 ve P< 0.01 düzeylerinde anlamlı olarak artığı tespit edildi. Serum Mg seviyesinin tüm deneme gruplarında kontrole göre istatistiksel olarak anlamlı derecede azaldığı tespit edildi (P< 0.01). L. casei strain Shirota ve yeșil çay ekstraktı alınması yüksek karbonhidrat diyetli gruplarda serum glikoz seviyesini yüksek lipid diyetli gruba göre anlamlı olarak azalttığı belirlendi (p< 0.05). SONUÇ: Yeșil çay ekstraktı ve L. casei strain Shirota kullanımının yüksek enerjili diyetle beslenen ratlarda kan glukoz ve trigliserid seviyelerini düșürücü etkisi vardır.