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The aim of this study was designed to evaluate the possible protective effects of thymoquinone (TQ) on the spermatogenesis after testicular injury caused by chronic toluene exposure in rats. The rats were randomly allotted into one of three experimental groups: control, toluene-treated and toluene treated with TQ; each group contained 10 animals. Control group received 1 mL serum physiologic and toluene treatment was performed by inhalation of 3000 ppm toluene, in an 8-hour/day and 6-day/week order for 12 weeks. The rats in TQ-treated group was given TQ (50 mg/kg body weight) once a day orally for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of testis in rats after chronic toluene exposure by TQ treatment have been reported. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in toluene treated groups when compared to the control group. Furthermore, the TQ-treated animals showed an improved histological appearance in toluene-treated group. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling (TUNEL), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of the toluene-treated group with TQ therapy. Electron microscopy of the testes of the rats demonstrated that pretreatment with TQ was particularly effective in preventing the mitochondrial degeneration, dilatation of smooth endoplasmic reticulum (SER) and enlarged intercellular spaces in both Sertoli and spermatid cells in the toluene-treated animals. We believe that further preclinical research into the utility of TQ may indicate its usefulness as a potential treatment on the spermatogenesis after testicular injury caused by chronic toluene exposure in rats.

The aim of this study was to evaluate the effects of methylene blue against cholestatic oxidative stress and liver damage after ligation of the common bile duct in male Wistar rats. Eight animals were included in each of the following five groups: untreated control, methylene blue control, sham-operated, bile-duct ligation, and bile-duct ligation plus methylene blue. Methylene blue was administered intraperitoneally for 14 days at a daily dose of 2mg/kg per day. All rats were sacrificed 2 weeks following the experimental treatment and the livers of all groups were examined biochemically and histopathologically. The severity of cholestasis and hepatic injury were determined by changes in the plasma, including enzymatic activities: aspartate aminotransferase, alanine aminotransferase, gamma glutamine transferase, and also bilirubin levels. Malondialdehyde, nitric oxide and superoxide dismutase were measured to indicate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined as measures of neutrophil activation and collagen accumulation, respectively. Liver damage was significantly prevented in the bile-duct ligated rats treated with methylene blue compared with the control bile-duct ligated rats without methylene blue. Treatment with methylene blue markedly reduced activities of serum transaminase, gamma glutamine transferase and bilirubin levels as compared to bile-duct ligated rats without methylene blue. Positive immunolabelling for alpha-smooth muscle actin (alpha-SMA) was increased, especially in vascular smooth muscle cells, fibrotic septa and also around the proliferated bile ducts, after bile-duct ligation. Only weak alpha-SMA immunolabelling was seen in livers of rats treated with methylene blue. These results indicate that methylene blue can attenuate hepatic damage in extrahepatic cholestasis by reducing oxidative stress and inflammatory processes.

We evaluated the effects of L-carnitine on apoptosis of germ cells in the rat testis following irradiation. Male Wistar rats were divided into three groups. Control group received sham irradiation plus physiological saline. Radiotherapy group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiotherapy + L-carnitine group received scrotal irradiation plus 200 mg/kg intraperitoneally L-carnitine. Twenty-four hours post-irradiation, the rats were sacrificed and testes were harvested. Testicular damage was examined by light and electron microscopy, and germ cell apoptosis was determined by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) technique. Morphologically, examination of irradiated testis revealed presence of disorganization and desquamation of germinal cells and the reduction in sperm count in seminiferous tubule lumen. Under electron microscopy, the morphological signs of apoptosis were frequently detected in spermatogonia. Apoptotic spermatogonia showed the marginal condensation of chromatin onto the nuclear lamina, nucleus and cytoplasm shrinkage and still functioning cell organelles. TUNEL-positive cells were significantly more numerous in irradiated rats than in control rats. L-carnitine treatment significantly attenuated the radiation-induced morphological changes and germ cell apoptosis in the irradiated rat testis. In conclusion, these results suggested that L-carnitine supplementation during the radiotherapy may be beneficial for spermatogenesis following testicular irradiation by decreasing germ cell apoptosis.

Aim: The protective effect of vitamin E (vit E) on cadmium (Cd) induced oxidative stress was studied in the blood of rats. Methods: The rats were randomly divided in to three experimental groups: Control, Cd treated and Cd + vit E treated, each contain-ing 10 animals. The Cd treated and Cd + vit E treated groups were injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl in the amount of 2 mL/kg for 20 days, resulting in a dosage of 0.49 mg Cd/kg/d. In addition, Cd + vit E treated group received intramuscular injection of 150 mg/kg vit E until the end of the study. Results: Cd treatment increased significantly malondialdehyde (MDA) levels and the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in plasma and erythrocytes compared to the control group. Cd + vit E treatment, decreased significantly elevated MDA lev-els in plasma and erythrocyte and also reduced significantly the enhanced antioxidant levels. Cd treatment increased significantly the activity of iron levels in the plasma compared to the control group. Cd + vit E treatment, decreased the activity of iron levels in the plasma compared to the Cd treated group. In the control group, the histology of erythrocytes was normal. In Cd treated group, there was marked membrane destruction and there were hemolytic changes in erythrocytes. In Cd + vit E treated group, these changes were less than Cd treated group. Conclussion: Our results show that vit E exerts a protective effect against cadmium toxicity.

The aim of this study was designed to investigate the possible beneficial effects of the thymoquinone (TQ) in streptozotocine (STZ)-induced diabetes in rats. The rats were randomly allotted into one of three experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with TQ); each group contain ten animals. B and C groups received STZ. Diabetes was induced in two groups by a single intra-peritoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/l citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in two experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting 2 days after STZ injection. Treatment of TQ reduced the glomerular size, thickening of capsular, glomerular and tubular basement membranes, increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. We conclude that TQ therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of TQ treatment may indicate its usefulness as a potential treatment in diabetic nephropathy.

The goal of this study was to evaluate the possible protective effects of sphingosylphosphorylcholine (SPC) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. Fifty-six animals were included in each of the following 7 groups: control, SPC control, phosphate-buffered solution control, sham operated, bile duct ligation (BDL), BDL plus phosphate-buffered solution, and BDL plus SPC. Sphingosylphosphorylcholine was administered 14 days at a daily dose of 2 μ m/mL intraperitoneally. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of aspartate aminotransferase, alanine aminotransferase, gama glutamin transferase, and levels of total bilirubin and direct bilirubin. Malondialdehyde, nitric oxide, and superoxide dismutase were determined to evaluate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined to assess neutrophil activation and collagen accumulation, respectively. Treatment with SPC markedly reduced serum transaminase activities as compared to BDL rats. Sphingosylphosphorylcholine also inhibited the increase in liver malondialdehyde; nitric oxide levels significantly and also attenuated the depletion of superoxide dismutase in the liver after BDL. Similarly, the increase in tissue myeloperoxidase activity and hydroxyproline owing to BDL was also attenuated by the SPC treatment. These data were supported by histopathologic findings. The α -smooth muscle actin–positive cells in the BDL were observed to be reduced with the SPC treatment. In conclusion, these findings suggested that SPC can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress, and inflammatory process. All these findings suggest that SPC may be a promising new therapeutic agent for cholestatic liver injury.

We have previously demonstrated that scrotal hyperthermia induce Leydig cell (LC) damage in short-term. The objectives of this pilot study were to investigate morphological changes and regulation of steroidogenesis on LC in long-term and the time of observation were extended to investigate whether the LC would eventually make a recovery after scrotal hyperthermia. The rats were randomly allotted into one of four groups: A (control), B (70 days after scrotal hyperthermia), C (105 days after scrotal hyperthermia), D (140 days after scrotal hyperthermia); each group contain seven animals. Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43 degrees C for 30 min once daily for six consecutive days. Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22 degrees C. Hyperthermia applied rats were sacrificed under 50 mg/kg ketamine anaesthesia after 70, 105 and 140 days, and biopsy materials of testes were obtained for light and electron microscopic examinations. Morphologically normal and the number of testosterone positive LC was significantly higher in 140 days after last heat than all other heat treatment groups. In heat treated groups, a dilated smooth endoplasmic reticulum, swollen mitochondria, and vanished mitochondrial cristae were observed. In the 140 days after scrotal hyperthermia, the severities of degenerative changes of LC were less than that observed in the other heat treated groups. We conclude that, scrotal hyperthermia cause morphological damaging and impaired steroidogenesis in LC and recovery of these findings were noted first time in 140 days after the last heat treatment.

Early oesophagoscopy is usually recommended in children after caustic ingestion to assess the severity of the initial digestive lesions. An oesophagoscopic procedure in children always demands to be performed under sedation and bears a certain risk of iatrogenic injury. The purpose of the study is to determine the value and sensitivity of Tc-99m pyrophosphate (99mTc-PYP) scintigraphy for the detection of caustic oesophageal injury.The caustic oesophageal burns were created with 25% NaOH in an experimental rat model. Seventeen rats were divided into two groups. The BURN group (n=9) included caustic oesophageal burning rats. Non-BURN group (n=8) included sham-operated rats. All animals underwent 99mTc-PYP scintigraphy 72 h after the burning experiment. Anterior static and single-photon emission computed tomography images were obtained using a low-energy all-purpose collimator, 2.55 zoom factor, 3h after intravenous injection of 10 mCi 99mTc-PYP. After the imaging, all the oesophagi were explored for external determination of the injury sites and macroautoradiographic scintigraphy as well. Rectangular region of interest were placed in the visually determined lesion of oesophagus (O) as well as non-lesion area (N), and an ON ratio was created. The severity and extension of oesophageal burn were assessed 3 days after burning by histopathologic evaluation. The injuries were graded according to the ulcer depth, ulcer width, thrombus formation, and the development of perivascular fibrinoid necrosis.The oesophageal burning areas were demonstrated by visual evaluation of the Tc-99m PYP scintigraphy on all animals. The mean ON ratio of 99mTc-PYP was 21.61+/-7.01 in the BURN group and in the non-BURN group, was 2.25+/-0.24 (p0.001). The best cut-off point of the ON ratio for caustic oesophageal injury was 5.45, with sensitivity and specificity of 100%. PYP scan findings were also confirmed by histological evidence of ulcer depth, ulcer width, thrombus formation, and perivascular fibrinoid necrosis in the same areas.The caustic oesophageal injuries have been demonstrated by 99mTc-PYP scintigraphy in burning experiment. 99mTc-PYP scintigraphy is sensitive for detection of caustic oesophageal injury. This new imaging tool is found to be sensitive and specific for the detection of caustic oesophageal injury in the rats.

An experiment was conducted using Bovans White layers to investigate the effects of 30% whole-wheat inclusion in a standard layer diet supplemented with xylanase, on laying performance, digestive organs and ileal mucosa development. Three dietary treatments were used: 1) control diet (30% ground wheat); 2) 30% whole wheat; 3) whole wheat+wheat xylanase. Xylanase was added to whole wheat at 150g/ton. Including the pre-experimental period the trial lasted for 13 weeks. Xylanase supplementation to whole wheat significantly (P

We have studied whether curcumin protects different pulmonary aspiration material-induced lung injury in rats. The experiments were designed in 60 Sprague–Dawley rats, randomly allotted into one of six groups (n = 10): normal saline (NS, control), enteral formula (Biosorb Energy Plus, BIO), hydrochloric acid (HCl), NS + curcumin-treated, BIO + curcumin-treated, and HCl + curcumin-treated. NS, BIO, HCl were injected in to the lungs. The rats received curcumin twice daily only for 7 days. Seven days later, both lungs in all groups were examined histopathologically, immunohistochemically, and biochemically. Histopathologic examination was performed according to the presence of peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation. Immunohistochemical assessments were examined for the activity of inducible nitric oxide synthase (iNOS) and the expression of surfactant protein D (SP-D). Malondialdehyde (MDA), hydroxyproline (HP), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity were measured in the lung tissue. Our findings show that curcumin inhibits the inflammatory response reducing significantly (P

The aim of the present study was to evaluate the radioprotective effect of vitamin C on gamma-radiation-induced damage to goblet cells of the ileum. Thirty male Wistar albino rats weighing between 250 and 300 g were randomized into the following study groups: I, control; II, single dose radiation treated; III, two dose radiation treated with a 4-day interval between doses; IV, single dose radiation treated with vitamin C; V, two dose radiation treated with vitamin C. Each group contained six animals. The rats in groups IV and V were given a daily dose of 100 mg/kg of vitamin C for 14 and 18 days, respectively. During the vitamin C administration period, the rats in group IV were exposed in the abdominal area to a gamma-ray dose of 5 Gy on day 10 and group V was exposed to same dose of radiation on days 10 and 14. Irradiation and treatment groups were decapitated 4 days after exposure to single or two dose irradiation and ileum tissues were removed for light and electron microscopic investigation. Single or two dose gamma-irradiation caused a marked intestinal mucosal injury in rats. Radiation produced increases in the number of goblet cells. Using transmission electron microscopy, extensions in the area between the cells, disorders in the microvilli, mitochondrial damage and endoplasmic reticulum (ER) cisternae dilatation were observed. Antioxidant treatment with vitamin C prior to irradiation provided protection against intestinal damage.

The major objective of this study was to test curcumin as a potential radioprotectant for the ileum goblet cells of the rat. Wistar albino rats were used in the study. Group A was the control group and group B was the single dose radiation group. Group C was the two dose radiation group (4 days interval). The rats in groups D and E were given a daily dose of 100 mg/kg of curcumin for 14 and 18 days, respectively. During the curcumin administration period, the rats in group D were exposed to abdominal area gamma (gamma)-ray dose of 5 Gy on the 10th day and group E was exposed to same dose radiation on the 10th and 14th day. Irradiation and treatment groups were decapitated on the 4th day after exposure to single or two-dose irradiation and ileum tissues were removed for light and electron microscopic investigation. Single or two dose 5 Gy gamma-irradiation caused a marked intestinal mucosal injury in rats on the 4th day. Radiation produced increases in the number of goblet cells. Curcumin appears to have protective effects against radiation-induced damage, suggesting that clinical transfer is feasible.

The aim of this study was to evaluate the efficiency of inducible nitric oxide synthase (iNOS) specific inhibitor, S-methylisothiourea sulfate (SMT) in preventing lung injury after different pulmonary aspiration materials in rats.The experiments were performed in 80 Sprague-Dawley rats, ranging in weight from 220 to 250 g, randomly allotted into one of the eight groups (n=10): normal saline (NS, control), Biosorb Energy Plus (BIO), sucralfate (SUC), hydrochloric acid (HCl), NS+SMT treated, BIO+SMT treated, SUC+SMT treated, and HCl+SMT treated. NS, BIO, SUC, HCl were injected in to the lungs in a volume of 2 ml/kg. The rats received twice daily intraperitoneal injections of 20 mg(kg day) SMT (Sigma Chemical Co.) for 7 days. Seven days later, rats were killed, and both lungs in all groups were examined immunohistochemically and histopathologically.Our data show that SMT inhibits the inflammatory response significantly reducing (p0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Furthermore, our data suggest that there is a significant reduction in the activity of iNOS and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with SMT therapy.It was concluded that SMT treatment might be beneficial in lung injury, therefore shows potential for clinical use.

The goal of this study was designed to evaluate the possible protective effects of Nigella sativa (NS) on the neuronal injury in the frontal cortex and brain stem after chronic toluene exposure in rats. The rats were randomly alotted into one of three experimental groups: A (control), B (toluene treated) and C (toluene treated with NS); each group contain 10 animals. Control group received 1 ml serum physiologic and toluene treatment was performed by inhalation of 3,000 ppm toluene, in a 8 h/day and 6 day/week order for 12 weeks. The rats in NS treated group was given NS (in a dose of 400 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex and brain stem after chronic toluene exposure in rats by NS treatment have been reported. In this study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, severely dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex and brain stem. The nerve cells showing the pathologic changes were almost absent in the NS-treated rats. We conclude that NS therapy causes morphologic improvement on neurodegeneration in frontal cortex and brain stem after chronic toluene exposure in rats. We believe that further preclinical research into the utility of NS may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.

The present study was performed to investigate whether the chronic administration of antioxidant vitamin C provided morphological protection on cisplatin-induced renal damage. Wistar albino male rats were divided into control and two experiment groups, each consisting of six rats. Cisplatin (5 mg/kg/month) was administered intravenously to the second and third group for three months. After the first application of cisplatin, vitamin C (8 mg/kg/day) to the third group was administered intramuscular for 3 months. At the end of the third month, the kidney specimens of the all groups were obtained. All of these kidney specimens were processed for light and electron microscopical examination. In the second group, most of the renal corpuscle lost their normal appearance and size, especially in the corticomedullary region. The most obvious changes were encountered in the proximal tubules. These changes were tubular dilation, thickening of basement membrane, loss of brush border, vacuolization, and swollenness of mitochondria in the proximal tubule epithelial cells. In addition, infiltration foci were observed mainly in the cortical region. In the third group, which was administered cisplatin plus vitamin C, although the structural damages and morphometric changes were lessened, mononuclear cell infiltration was still observed. This study suggests that the chronic administration of vitamin C may be of therapeutic benefit on cisplatin nephrotoxicity.

Objective: The aim of the study was to determine the protective effect of curcumin on testicular ischemia-reperfusion (I/R) injury. Materials and Methods: 32 male rats were divided into four groups (n = 8): group 1: control; group 2: ischemia; group 3: I/R, and group 4: I/R+CUR. Curcumin (150 mg/kg, p.o.) was administered before 30 min of reperfusion in group 4. Malondialdehyde (MDA) levels, Johnsen’s testicular biopsy scores, and mean seminiferous tubule diameter measurements were evaluated in testes. In addition, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expressions were evaluated immunohistochemically. Results: MDA levels in control groups were significantly lower than other groups in ipsilateral and contralateral testes. Johnsen’s scores in the control group were significantly higher than in other groups. MDA levels and Johnsen’s scores in the I/R+CUR group were similar to the ischemia and I/R groups in ipsilateral and contralateral testes. The immunoreactivity of iNOS and eNOS were increased in I/R ipsilateral testicular groups. After I/R, iNOS and eNOS expression increased slightly in contralateral groups. Additionally, the curcumin treatment decreased iNOS and eNOS immunoreactivity in ipsilateral and contralateral testes. Conclusion: The results suggest that curcumin did not protect the unilateral nor contralateral testes. This observation may depend on inhibition of iNOS and eNOS due to inhibition of the antioxidant, anti-inflammatory effects of nitric oxide.

Day-old male chicks were used to test the effects of a combination of formic and propionic acids (CFP) added to wheat- and barley-based diets on the performance and gut histomorphology of broilers. The CFP, containing formic and propionic acids based on an inorganic phyllo-silicate carrier, was added to starter and grower broiler diets of standard (NRC, 1994) or lower nutrient density (LND) using different levels of wheat and barley. Body weight gain (BWG) and feed conversion ratio (FCR) of broiler chicks were significantly (P < 0.001) improved by CFP supplementation at 21 days of age regardless of nutrient density (ND). However, at 35 days of age CFP addition significantly (P < 0.001) increased BWG and FCR. Proventriculus weight was also significantly affected by the dietary treatments. Ileal viscosity was significantly (P < 0.05) affected by ND which was associated with wheat and barley contents, whereas feed viscosity was significantly (P < 0.05) affected by CFP supplementation. Villus height was significantly (P < 0.05) increased by the CFP supplementation. In the case of villus width, an interaction effect was observed: there was a significant (P < 0.05) decrease in the group fed the standard ND diet, but only a numerical decrease in the group fed the LND diet compared to control group. No significant effect of dietary treatment on the thickness of the lamina muscularis mucosae could be detected.

The aim of this study was designed to investigate the possible beneficial effects of Nigella sativa (NS) and derived thymoquinone (TQ) on neurodegeneration in hippocampus after chronic toluene exposure in rats. The rats were randomly allotted into one of four experimental groups: A (control), B (toluene treated), C (toluene treated with NS) and D (toluene treated with TQ); each group contain 10 animals. Toluene treatment was performed by inhalation of 3,000 ppm toluene, in a 8 h/day and 6 day/week order for 12 weeks. Control group received 1 ml serum physiologic and the rats in NS and TQ treated groups (C and D) were given NS (in a dose of 400 mg/kg body weight) and TQ (50 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting just after toluene exposure respectively. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in hippocampus after chronic toluene exposure in rats by NS and TQ treatment have been reported. In this study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, slightly dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the hippocampus. The distorted nerve cells were mainly absent in the TQ and NS-treated rats. We conclude that TQ and especially NS therapy causes morphologic improvement on neurodegeneration in hippocampus after chronic toluene exposure in rats. We believe that further preclinical research into the utility of NS and TQ may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.

The aim of this study was designed to investigate the possible beneficial effects of Nigella sativa (NS) and thymoquinone (TQ) on histopathological changes of sciatic nerves in streptozotocin-induced diabetic rats. The rats were randomly allotted into one of four experimental groups: A (control), B (diabetic untreated), C (diabetic treated with NS) and D (diabetic treated with TQ); each group contain ten animals. B, C and D groups received streptozotocin (STZ) to induce diabetes. The rats in NS and TQ treated groups were given NS (in a dose of 400 mg/kg body weight) and TQ (50 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Blood and tissue samples were obtained for biochemical and histopathological investigation. The treatment of both NS and TQ caused a sharp decrease in the elevated serum glucose (P < 0.01, 0.05, respectively), and an increase in the lowered serum insulin concentrations (P < 0.01, 0.05, respectively), in STZ-induced diabetic rats. STZ induced a significant decrease in the area of insulin immunoreactive β-cells (P < 0.0001). NS (P < 0.001) and TQ (P < 0.01) treatment resulted in increased area of insulin immunoreactive β-cells significantly. To date, no histopathological changes of sciatic nerves in STZ induced diabetic rats by NS and TQ treatment have been reported. In this study, histologic evaluation of the tissues in diabetic animals treated with TQ and especially NS showed fewer morphologic alterations. Myelin breakdown decreased significantly after treatment with NS and TQ. The ultrastructural features of axons also showed remarkable improvement. We believe that further preclinical research into the utility of NS and TQ may indicate its usefulness as a potential treatment on peripheral neuropathy (PN) in STZ induced diabetic rats.

Extracts of the seeds of Nigella sativa (NS), an annual herbaceous plant of the Ranunculaceae family, have been used for many years for therapeutic purposes, including their potential anti-diabetic properties. The aim of the present study was to test the hypothesis that combined treatment with NS and human parathyroid hormone (hPTH) is more effective than treatment with NS or hPTH alone in improving bone mass, connectivity, biomechanical behaviour and strength in insulin-dependent diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) at a single dose of 50 mg/kg. The diabetic rats received NS (2 ml/kg/day, i.p.), hPTH (6 µg/kg/day, i.p.) or NS and hPTH combined for 4 weeks, starting 8 weeks after STZ injection. The ß-cells of the pancreatic islets of Langerhans were examined by immunohistochemical methods. In addition, bone sections of femora were processed for histomorphometry and biomechanical analysis. In diabetic rats, the ß-cells were essentially negative for insulin-immunoreactivity. NS treatment (alone or in combination with hPTH) significantly increased the area of insulin immunoreactive ß-cells in diabetic rats; however, hPTH treatment alone only led to a slightly increase in the insulin-immunoreactivity. These results suggest that NS might be used in a similar manner to insulin as a safe and effective therapy for diabetes and might be useful in the treatment of diabetic osteopenia. © 2007 Elsevier GmbH. All rights reserved.

The aim of this study was to evaluate the efficiency of methylene blue (MB) in preventing renal scar formation after the induction of pyelonephritis (PNP) in a rat model with delayed antimicrobial therapy. An inoculum of the K-12 strain of Escherichia coli was injected into both kidneys. Control groups received isotonic saline instead of bacterial solution. Four equal groups were then formed: the PNP group was untreated and the PNP ciprofloxacin (CIP) treated group was treated only with CIP intraperitoneally (i.p.) starting on the third day following bacterial inoculation. In the PNP (MB)-treated group, MB was given i.p., and in the PNP MB + CIP-treated group, MB + CIP were administered i.p.. In the sixth week following bacterial inoculation, all rats were sacrificed, and both kidneys of the rats in all groups were examined biochemically and histopathologically for renal scarring. Renal scar was significant in the groups treated with MB alone or MB + CIP combination compared with untreated or antibiotic only groups. Delayed treatment with antibiotics had no effect on scarring. These results suggest that the addition of MB to the delayed antibiotic therapy might be beneficial in preventing PNP-induced oxidative renal tissue damage.

The aim of this study was to assess the effect of Ginkgo biloba extract (EGb 761) on healing of experimental colonic anastomoses in a rat model. Rats were divided into four groups: postoperative day (POD) 3 untreated control group, POD 3 EGb 761 group, POD 7 untreated control group, and POD 7 EGb 761 group. In the oral EGb 761 groups, the agent was given at 9.6 mg daily per orogastric route using a 4-F fine feeding catheter. We measured bursting pressures and hydroxyproline content and histologically examined the resected anastomoses on POD 3 and POD 7. The bursting pressures increased more in the EGb 761 group than in the untreated control group on POD 3, but this difference was not statistically significant. Hydroxyproline content was higher in the EGb 761 group than in the untreated control group on POD 3, and this difference was statistically significant. Anastomosis bursting pressure values and hydroxyproline contents were significantly higher in the EGb 761 group than in the untreated control group on POD 7. Histological examination showed greater fibroblastic activity in the EGb 761 group than in the untreated control group on POD 3. There was no significant difference in anastomotic polimorphonuclear leukocyte, mononuclear cells and blood vessel neodevelopment between the POD 3 groups, but there was significant difference in fibroblastic activity and blood vessel neodevelopment between the POD 7 groups. These results showed us that EGb 761 administration resulted in enhanced stability of colonic anastomoses during the first postoperative week.

1. Rosiglitazone plays a positive role in the reparation of ischaemia-reperfusion (I/R) injury in different tissues. Thus, we examined its biochemical and histological effects on the contralateral testes to determine whether exogenous rosiglitazone affords any protection against testicular damage. 2. Forty-eight prepubertal male Wistar-Albino rats were divided into six groups. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction for 5 h in all groups except group I, which was the sham-control group. In group II, bilateral orchiectomy was performed following the torsion period. After detorsion both testes were removed in the fifth hour in group III and on the seventh day in group IV. In group V, one-shot rosiglitazone (4 mg/kg) was administered 40 min before detorsion and both testes were removed following the torsion period. In group VI, rosiglitazone was administered (4 mg/kg) 40 min before detorsion and for 7 days, and then both testes were harvested. The tissue levels of malondialdehyde (MDA) were measured and mean testicular biopsy score (MTBS) and mean seminiferous tubule diameter (MSTD) were examined. Immunoexpression of endothelial nitric oxide synthase (eNOS) in testes tissues was investigated by immunohistochemical studies. 3. In the contralateral testis, the MTBS and MSTD values of group VI were significantly higher than those in group IV. Immunohistochemically, mild eNOS immunostaining was present in the germ cells of the contralateral testes in group IV after I/R. In group VI, intense eNOS immunoreactivity was seen in the contralateral testes. 4. Rosiglitazone reduces contralateral testicular damage formed after unilateral testicular torsion and alleviates the oxidative events.

The experiment was conducted to study the effects of supplementing a broiler starter diet with the probiotic Enterococcus faecium NCIMB 10415 and dried whey (80% lactose) on chick performance, gut histomorphology and intestinal microbiota. One-day-old male Ross 308 strain broiler chickens were fed diets containing: (i) control feed, (ii) control + 3.5% dried whey, (iii) control + 0.2% E. faecium, and (iv) control + 3.5% dried whey + 0.2% E. faecium. Birds were maintained in battery brooders confined in an environmentally controlled experimental room. The experiment lasted for 21 days. Birds fed E. faecium or E. faecium + dried whey exhibited significantly improved weight gain and feed conversion rate (FCR). Weight gain and FCR of treatment groups 1-4 were 628.7, 657.8, 690.9, 689.3 and 1.218, 1.193, 1.107, 1.116, respectively. Lactic acid bacteria counts in both the ileal content and excreta were significantly affected by dietary treatment. Supplementation of the E. faecium and dried whey separately and in combination increased lactic acid bacteria colonization in the ileal content from 4.2 to 5.0, 7.8 and to 5.1 log cfu/g, respectively (treatments 1-4). Similarly, supplementation of dried whey and E. faecium separately and in combination increased lactic acid bacteria in the excreta from 5.3 to 5.5, 8.0 and to 7.2 log cfu/g, respectively. Addition of the probiotic E. faecium increased villus height in the ileum (p < 0.05). Thus, supplementation of E. faecium enhanced broiler chick performance with respect to weight gain and FCR. No additive effect of E. faecium and dried whey was detected. Further studies are needed to investigate the relationship between E. faecium and dried whey with respect to gut histomorphology.

This study was designed to investigate the effect of Nigella sativa (NS), in reperfusion-induced renal injury in rats.A total of 24 male Sprague-Dawley rats were divided into 3 groups of controls and rats that underwent ischemia-reperfusion with and without pretreatment with NS. A rat model of renal reperfusion injury was induced by 45-minute occlusion of the bilateral renal pedicles and 24-hour reperfusion. In the NS group, a single dose NS (400 mg/kg orally) was administered by gastric gavage.Renal reperfusion caused severe histopathological injury such as tubular damage, atrophy dilatation, loss of brush border, and hydropic epithelial cell degenerations. Treatment with NS significantly attenuated the severity of reperfusion injury and significantly lowered tubulointerstitial damage score as compared with the reperfusion group. When kidney sections were stained with anti-proliferating-cell nuclear antigen antibody, nuclear factor kappaB p65 antibody, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, there was a clear increase in the number of positive cells in the reperfusion group in the renal cortical tissues. However, there was a significant reduction in the number of stain-positive cells in kidney tissue from the NS group. Treatment of renal reperfusion injury with NS decreased the elevated tissue malondialdehyde levels and increased the reduced activities of the enzymatic antioxidants glutathione peroxidase and catalase.Pretreatment with NS has a protective effect against renal damage induced by renal reperfusion. This protective effect is possibly due to its ability to inhibit reperfusion-induced renal damage, apoptosis, and cell proliferation.

The most prevalent malignant ovarian neoplasms are epithelial ovarian cancers which is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of survivin and cycline D1 biomarkers in mucinous ovarian neoplasms and their correlations with clinicopathological variables in mucinous ovarian cancers. We analyzed pathological specimens of 98 patients with benign (n = 34), borderline (n = 22) and malignant (n = 42) mucinous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Immunohistochemical analysis revealed that survivin and cyclin D1 expressions were located primarily in the nucleus of ovarian tumor cells and relatively weaker cytoplasmic staining. Survivin expression was significantly higher in malignant tumors (88.1 %) than those found in borderline (18.2 %) and benign tumors (8.8 %) (p < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (100 %) compared to borderline (36.4 %) and benign tumors (5.9 %) (p < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant mucinous tumors. In terms of clinicopathological variables, tumor grade, FIGO stage and lymph node methastasis were associated with the expression of both biomarkers. Whereas age exhibited no different correlations in mucinous ovarian cancers. The expressions of survivin and cycline D1 are positively correlated with the malignant potential of mucinous ovarian neoplasms.

Introduction The aim of this study was to compare the efficacy of Nigella sativa in protection of jejunal mucosa against harmful effects of gamma radiation. Methods Radiotherapy group received abdominal gamma radiation of 15 Gy in addition to physiological saline. Radiotherapy + Nigella sativa treatment group received abdominal gamma radiation of 15 Gy in addition to Nigella sativa treatment in the amount of 400 mg/kg. Radiotherapy and treatment groups were sacrificed 3 days after the exposure to irradiation. Then, jejunum samples were harvested for biochemical and histological assessment of mucosal injury. Results Nigella sativa treatment was found to significantly lower elevated tissue malondialdehyde (MDA) levels and, to raise reduced glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity in intestinal tissues samples. Single dose 15 Gy gamma-irradiation was noted to result in a marked jejunal mucosal injury. Three days after exposure to irradiation, the villi and Lieberkuhn crypts were observed as denuded, and villous height diminished. Concomitantly with inflammatory cell invasion, capillary congestion and ulceration were observed in the atrophic mucosa. Nigella sativa treatment significantly attenuated the radiation induced morphological changes in the irradiated rat jejunal mucosa. Conclusion Nigella sativa has protective effects against radiation-induced damage, suggesting that clinical transfer is feasible.

Cadmium (Cd) is a serious environmental and occupational contaminant and may represent a serious health hazard to humans and other animals. Cd is reported to induce the generation of reactive oxygen species, and induces testicular damage in many species of animals. The goal of our study was to examine the anti-apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd-induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40 male Wistar albino rats were divided into four groups: control, CAPE alone, Cd-treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 30 days. The rats in CAPE-treated group were given a daily dose of 10 μmol/kg body weight of CAPE by using intraperitoneal injection. This application was continued daily for a total of 30 days. To date, no examinations of the anti-apoptotic and anti-oxidant properties of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat testes have been reported. CAPE-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the number of apoptotic cells in testis tissues of the Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes tissue resulted from Cd administration. These findings suggest that the protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced testicular injury.

Cadmium (Cd), an environmental and industrial pollutant, generates free radicals responsible for oxidative stress. Cd can also lead to various renal toxic damage such as the proximal tubules and glomerulus dysfunction. Thymoquinone (TQ) is the main constituent of the essential oil obtained from black seeds (Nigella sativa) and has various pharmacological effects. The aim of the present study was to examine the nephroprotective, anti-oxidant, and anti-apoptotic effect of the TQ against Cd-induced nephrotoxicity. A total of 24 male Wistar albino rats were divided into three groups: control, Cd-treated, and Cd-treated with TQ; each group contain eight animals. The Cd-treated group was injected subcutaneously with CdCl2 dissolved in saline in the amount of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in TQ-treated groups were given TQ (50 mg/kg body weight) once a day orally together with first Cd injection during the study period. The histopathological studies in the kidney of rats also showed that TQ markedly reduced the toxicity of Cd and preserved the normal histological architecture of the renal tissue. Immunohistochemical analysis revealed that TQ significantly decreased the Cd-induced over expression of nuclear factor-κB in renal tissue. Furthermore, TQ treatment resulted in decreased the number of apoptotic cells. TQ significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses (reduced superoxide dismutase, glutathione peroxidase and catalase activities) in renal tissue resulted from Cd administration. These findings suggest that the nephroprotective potential of TQ in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced nephrotoxicity.

In this study, we aimed to show how cadmium (Cd) affects the trophoblast proliferation and differentiation in the placenta and the apoptotic activity in different gestational days and, hence, its effects of placental development with immunohistochemical and TUNEL techniques. Experimental model of our study consisted of placental development of control and Cd groups on 15, 17, 19, and 21th days of the gestation. Female rats in Cd groups were subcutaneously administered a single dose of 0.5 mg Cd/kg/day dissolved in sodium chloride as 2 mL/kg Cd chloride until the day they sacrificed. Embryo and placenta of female rats were separately removed on 15, 17, 19, and 21th days of the gestation in which the placental development takes place and placentas were processed for microscopic examinations. In the placentas of the control group, all layers were observed to be formed on the 15th gestational day and thereafter a continuous growth was monitored. In the Cd group also all layers existed from the 15th gestational day. However, they were smaller in size than control groups. Frequency of proliferating cell nuclear antigen (PCNA)-positive cells was decreased and the number of apoptotic cells was increased in all the gestational days related to Cd. In conclusion, Cd administered during the pregnancy was observed to cause abnormal placental development by disrupting the normal structure of the placenta, inhibiting the proliferation of trophoblast and increasing the number of apoptotic trophoblast cells.

Aim: This study was designed to investigate the effects of gonadotropin-releasing hormone agonist (GnRHa) on the ovulation rate, the oocyte number and maturation in mice superovulated with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Methods: Thirty female mice, aging 3 months and weighing between 25-30 g, were assigned to the three experimental groups of control, superovulated and GnRHa treated, each containing 10 animals. Control mice were received only the intraperitoneal (i.p.) injection of 0.1 ml 0.9% NaCl. Superovulated mice were given an i.p. injection of 5 IU of eCG followed 48 hr later by 5 IU of hCG injection (i.p.). The GnRHa treated mice were received an intramuscular (i.m.) injection of a 20 mg/kg GnRHa (buserelin) 24 hr before the superovulation with eCG -hCG. Thirteen hr after hCG administration, mice were sacrificed by cervical dislocation. The ovaries and the fallopian tubes were also harvested for counting the corpora lutea and cumulus-enclosed oocytes. Results: The oocyte number and the maturation, ovulation rate, and the corpus luteum number were higher in GnRHa treated mice than controls and superovulated mice. Conclusion: It is concluded that an i.m. injection of the GnRHa 24 hr before the superovulation with eCG-hCG increases the oocyte number and maturation, and ovulation rate, thus, could be used for in vivo and in vitro fertilizations. Keywords: GnRH agonist, Superovulation, Oocyte maturation, Mice.

Aim: The aim of the study was to investigate the histological appearance of testis, epididymis, prostate and seminal vesicles of ram lambs immunized against gonadotrophin releasing hormone (GnRH). Methods: The study was performed on 14 male lambs, 7 in the study group and the other 7 in the control group. Another 5 lambs were included from the study after biopsy samples were taken from their testes at age 10 weeks to determine testicular histology at the start of the study. Seven male lambs aged 10 weeks were immunized against GnRH using a recombinant GnRH fusion protein vaccine. The immunization was repeated twice monthly until slaughter at 9 months of age. Testes and epididymis biopsies were taken at the 6th month. After slaughter, testis, epididymis, prostate and seminal vesicles were extracted for histopathological investigation. Results: At the 6th month and at slaughter histopathology of all the sex glands, most evidently in the testes, indicated secondary infertility. In the study group, tubule diameter decreased and spermatogenetic activity disappeared. The ball of sperm cells seen in the epididymis tubules of the control group at the 9th month was not seen in the study group. Changes in prostate tissues between the study and control groups were not evident but stromal tissue in the seminal vesicles increased in the study group. Conclusion: In conclusion, the histomorphological changes showed that recombinant GnRH fusion proteins provided immune castration in male lambs when used at an early age.

The aim of the present study was to assess the influence of quercetine (QE) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Wistar albino rats were divided into three groups: sham-operated (SH), PH and PH+QE; each group contain 8 animals. The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day i. p., for 7 days starting 3 days prior to hepatectomy operation. At 7 days after resection, liver samples were collected. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labelling, proliferation index (PI), transferase-mediated dUTP nick end-labelling assay, apoptotic index (AI) were evaluated at 7 days after hepatectomy. As a result, QE significantly increased MI, PI, and significantly decreased AI in PH rats. Additionally, QE remarkably inhibited the elevation of MDA, restored impaired antioxidant SOD activity and GSH level, and also attenuated hepatic vacuolar degeneration and sinusoidal congestion. These results suggested that QE treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic and proliferative property.

N-acetylcysteine (NAC) is a precursor of glutathione, a potent antioxidant, and a free radical scavenger. The beneficial effect of NAC on nervous system ischemia and ischemia/reperfusion models has been well documented. However, the effect of NAC on nervous system trauma remains less understood. Therefore, we aimed to investigate the therapeutic efficacy of NAC with an experimental closed head trauma model in rats. Thirty-six adult male Sprague–Dawley rats were randomly divided into three groups of 12 rats each: Group I (control), Group II (trauma-alone), and Group III (trauma+NAC treatment). In Groups II and III, a cranial impact was delivered to the skull from a height of 7 cm at a point just in front of the coronal suture and over the right hemisphere. Rats were sacrificed at 2 h (Subgroups I-A, II-A, and III-A) and 12 h (Subgroups I-B, II-B, and III-B) after the onset of injury. Brain tissues were removed for biochemical and histopathological investigation. The closed head trauma significantly increased tissue malondialdehyde (MDA) levels (P

Aim: This study was evaluated to investigate the efficacy of Ebselen, which is an organoselenium compound and glutathione peroxidase mimic, on the prevention of stricture development after esophageal caustic injuries in the rat. Methods: Thirty healthy male Wistar albino rats were utilized in this study. The rats were randomly allotted into one of three experimental groups: group A (sham) animals were uninjured. Caustic esophageal burn was created by applying 1 ml of 37.5% NaOH to the distal esophagus. Group B rats were injured but untreated. Group C rats were injured and received Ebselen (10 mg/kg/day) via the oral route. Blood and tissue samples for the biochemical and histopathological analysis were taken all rats at the end (28th day) of the experiment. Oxidative stress is believed to play a role in the pathogenesis of corrosive esophageal burns. To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in esophagus homogenates. We also measured esophageal tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Efficacy of the treatment was assessed by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content, lipid peroxidation and antioxidant enzyme levels. Results: The stenosis index in group B was significantly increased compared with group A and C (P < 0.05). The hydroxyproline level was significantly increased in group B compared with group A and C (P < 0.05). In group B, the histopathologic damage score was significantly higher than in group C (P < 0.05). Treatment with Ebselen decreased tissue hydroxyproline levels, histological damage, and the stenosis index. Caustic esophageal burn increased the lipid peroxidation and also decreased the antioxidant enzyme levels in group B. Ebselen treatments for 28 days decreased the elevated lipid peroxidation and also increased the reduced antioxidant enzyme levels. Live weights of the rats was significantly decreased in group B compared with group A and C (P < 0.05). Conclusion: It is concluded that Ebselen has a preventive effect in the development of fibrosis and decrease the lipid peroxidation, and increase the antioxidant defense system activity in an experimental model of corrosive esophagitis in rats. © 2005 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic saline (10 ml kg(-1)) and the ethanol group had taken 1 ml (per rat) absolute alcohol by gavage. The third and fourth groups also received NS (500 mg kg(-1)) and TQ (10 mg kg(-1)) by gavage 1 h before alcohol administration, respectively. Both drugs (NS and TQ) could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index values. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells (MC) and gastric erosions in ethanol treated rats. The NS treatment significantly decreased the number of MC and reduced the area of gastric erosions. Likewise, TQ treatment was also able to reduce the number of MC and the gravity of gastric mucosal lesions, but to lesser extent compared to NS. Gastric tissue histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats, and NS or TQ treatment reversed these increases. Results obtained from this study suggest that both drugs, particularly NS could partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects could be due to their antiperoxidative, antioxidant and antihistaminic effects.

The protective effect of black cumin (Nigella sativa = NS) on cadmium-induced oxidative stress was studied in rats. The rats were randomly divided into three experimental groups: A (conrol), B (Cd treated), and C (Cd + NS treated), each containing 10 animals. The Cd-treated and Cd + NS-treated groups were injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl in the amount of 2 mL/kg for 30 d, resulting in a dosage of 0.49 mg Cd/kg/d. The control group was injected with only isotonic NaCl (2 mL/kg/d) throughout the experiment (for 30 d). Three days prior to induction of CdCl 2, the Cd + NS-treated group received a daily intraperitoneal injection of 0.2 mL/kg NS until the end of the study. Cd treatment increased significantly the malondialdehyde levels in plasma and erythrocyte (p

This study was designed to investigate the effects of chronic toluene inhalation in high concentration on lipid peroxidation, antioxidant enzyme activities and ultrastructural changes in the sciatic nerves of rats. Male Wistar albino rats (150-250 g) were divided in two experimental groups: the control and the toluene treated group (n = 10 for each). Toluene treatment was performed by inhalation of 3000 ppm toluene, in a 8 h/day and 6 day/week order for 16 weeks. Blood and tissue samples were obtained for biochemical and histopathological investigation. The blood and sciatic nerves were assayed for toluene by gas chromatography. Toluene significantly increased blood and tissue malondialdehyde (MDA), and decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not tissue catalase (CAT) levels when compared with controls. Electron micrographs of sciatic nerve in the toluene group shows myelin destructions with onion-bulb and bubble form protrusion on the myelin sheath and axolemma border of myelinated axons. The area of injury on the myelin sheath were measured by Image-Pro Plus. Mean of the injury area were estimated 34% each myelin. These findings indicate that chronic toluene inhalation might be involved with free radical processes.

WOS: 000228824400010, PubMed: 15888972, This study was designed to investigate the protective effects of vitamin C and vitamin A on oxidative renal tissue damage. Male Wistar rats were given an intraperitoneal injection of 0.5 ml saline (control) or 0.5 ml solution of lipopolysaccharide (10 mg/kg), which caused endotoxemia. Immediately (within 5 min) after the endotoxin injection, the endotoxemic rats were untreated or treated with intraperitoneal injection of vitamin A (195 mg/kg bw), vitamin C (500 mg/kg bw) or their combination. After 24 hours, tissue and blood samples were obtained for histopathological and biochemical investigation. Endotoxin injection caused renal tissue damage and increased erythrocyte and tissue malondialdehyde (MDA) and serum nitric oxide (NO), urea and creatinine concentrations, but decreased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared to the parameters of control animals. Treatment with vitamin C or with vitamins C and A significantly decreased the MDA levels and serum NO, urea and creatinine levels, recovered the antioxidant enzyme activities (SOD, GSH-Px and CAT), and prevented the renal tissue damage in endotoxemic rats. In contrast, vitamin A alone did not change the altered parameters except for creatinine levels. Notably, the better effects were observed when vitamins A and C given together. It is concluded that vitamin C treatment, alone or its combination with vitamin A, may be beneficial in preventing endotoxin-induced oxidative renal tissue damage and shows potential for clinical use. - endotoxemia; vitamin A; vitamin C; malondialdehyde; kidney (c) 2005 Tohoku University Medical Press.

Free radicals have been reported to be responsible for many ailments including gastroduodenal ulcers. Recent studies demonstrated that quercetin (QE) has an antioxidant effects on injuries caused by various toxic agents in different experimental models. In our study, we examined anti-ulcerogen and antioxidant effects of quercetin on ethanol-induced gastric lesions in rats. QE was administered intraperitoneally (i.p.) 50 mg/kg. It was found that pretreatment with QE significantly reduced ethanol-induced gastric damage and malondialdehyde levels, and significantly increased antioxidant enzyme activities. We conclude that QE clearly has antioxidant properties and that the protective effect of QE against ethanol-induced gastric mucosal lesion, at least in part, depends upon the reduction in the lipid peroxidation and an increase in the activity of antioxidant enzymes.

WOS: 000222466000012, PubMed: 15224410, The aim of the present study was to evaluate the possible protective effects of Nigella sativa L. (NS) against beta-cell damage from streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. NS (0.2 ml/kg/day, i.p.) was injected for 3 days prior to STZ administration, and these injections were continued throughout the 4-week study. Oxidative stress is believed to play a role in the pathogenesis of diabetes mellitus (DM). To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in pancreatic homogenates. We also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Pancreatic beta-cells were examined by immunohistochemical methods. STZ induced a significant increase in lipid peroxidation and serum NO concentrations, and decreased antioxidant enzyme activity. NS treatment has been shown to provide a protective effect by decreasing lipid peroxidation and serum NO, and increasing antioxidant enzyme activity. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of beta-cell numbers were apparent in the NS-treated diabetic rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing oxidative stress and preserving pancreatic beta-cell integrity. Consequently, NS may be clinically useful for protecting beta-cells against oxidative stress. (C) 2004 Wiley-Liss, Inc.

This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200-220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on d 13 of pregnancy by a single intraperitoneal injection of STZ in the STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on d 13 of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on d 15 and d 20 of pregnancy. Blood samples were taken for determination of the serum glucose and insulin levels. Fetal and maternal livers of sacrificed rats in all groups were harvested on d 15 and d 20 of pregnancy, whereas placentas were harvested only on d 20 of pregnancy for histochemical examination. Although both Cd and STZ caused hyperglycemia and decreased insulin secretion, Cd-alone treatment increased the glycogen content only in the placental labyrinth, whereas STZ-alone treatment increased the glycogen content only in the maternal part of the placenta. Increased glycogen localization was observed in both the placental labyrinth and the maternal part of placenta when Cd and STZ were given together. Fetal and maternal livers of control and other treatment groups were not different regarding the glycogen content on d 15 or d 20 of pregnancy. It was concluded that Cd exposure during pregnancy might produce a glycogen localization in the placenta of diabetic rats. However, the function and the mechanisms of increased glycogen contents in the placenta of Cd-exposed pregnant diabetic rats remain unclear and further studies are needed.

Ovarian cancer is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of HER-2/neu (c-erbB2), survivin and cycline D1 biomarkers in serous ovarian neoplasms and their correlations with clinicopathological variables in serous ovarian cancers. We analyzed pathological specimens of 62 patients with benign (n = 25), borderline (n = 14) and malignant (n = 23) serous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Significantly more immunoreactivity with HER-2/neu was detected in malignant tumors (100 %) compared to borderline (78.6 %) and benign tumors (48 %) (P < 0.01). Survivin expression was significantly higher in malignant tumors (91.3 %) than those found in borderline (71.4 %) and benign tumors (24 %) (P < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (95.6 %) compared to borderline (85.7 %) and benign tumors (48 %) (P < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant serous tumors. In terms of clinicopathological variables, only tumor grade was associated with the expression of all biomarkers others exhibited different correlations in serous ovarian cancers. The expressions of HER-2/neu (c-erbB2), survivin and cycline D1 are positively correlated with the malignant potential of serous ovarian neoplasms.

We investigated the effects of ionizing radiation on maturation ability and radiosensitivity of oocytes enclosed in preantral and antral follicles. Balb/c female mice received total body single dose gamma radiation (7.2 Gy) at the diestrous to proestrous transition period. In the first experiment, spontaneously ovulated oocytes were collected from irradiated animals. In the second experiment, irradiated animals were allowed to superovulate to assess the ovarian function. The spontaneous ovulation rate of the follicles exposed at antral stage was significantly lower than the sham-irradiated mice (p < 0.01), and most of the oocytes were found at the metaphase I stage. Oocyte morphology and the ovulation rate of the follicles exposed at preantral stage were similar to the sham-irradiated group. Minimal morphological abnormalities were observed in the oocytes and the polar body as well. The superovulation response of all the irradiated animals was lower than the respective control animals. The superovulation rate was significantly lower in the first ovulation after irradiation (p < 0.01). In conclusion, our findings indicate that total body gamma irradiation, on a basis of estrous cycle stages, leads to ovulation failure in the antral stage while causes abnormal oocyte morphology in the preantral stage follicles in mice.

AIM: The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. MATERIAL and METHODS: 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. RESULTS: While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1 beta level was significantly increased in the EMR groups in the brain stem. CONCLUSION: EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development. Turkish Neurosurgery Society Scientific Research Committee This study was supported by the Turkish Neurosurgery Society Scientific Research Committee. The authors alone are responsible for the content and writing of the paper.

The purpose of the present investigation was to evaluate cadmium (Cd)-induced neurotoxicity in hippocampal tissues and beneficial effect of quercetin (QE) against neuronal damage. A total of 30 male rats were divided into 3 groups: control, Cd-treated, and Cd + QE-treated groups. After the treatment, the animals were killed and hippocampal tissues were removed for biochemical and histopathological investigation. Cd significantly increased tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD) and catalase (CAT) enzyme activities in hippocampal tissue compared with the control. Administration of QE with Cd significantly decreased the levels of MDA and PC and significantly elevated the levels of antioxidant enzymes in hippocampal tissue. In the Cd-treated group, the neurons of both tissues became extensively dark and degenerated with pyknotic nuclei. The morphology of neurons in Cd + QE group was well protected, but not as neurons of the control group. The caspase-3 immunopositivity was increased in degenerating neurons of the Cd-treated group. Treatment of QE markedly reduced the immunoreactivity of degenerating neurons. The results of the present study show that QE therapy causes morphologic improvement in neurodegeneration of hippocampus after Cd exposure in rats.

The present study was performed to investigate the effect of Urtica dioica (UD) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Sprague Dawley rats were divided into three groups: sham-operated, PH and PH + UD; each group contains eight animals. The rats in UD-treated groups were given UD oils (2 ml/kg/day) once a day orally for 7 days starting 3 days prior to hepatectomy operation. At day 7 after resection, liver samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labeling, proliferation index (PI), transferase-mediated deoxyuridine triphosphate nick end-labeling assay, apoptotic index (AI) were evaluated at day 7 after hepatectomy. As a result, UD significantly increased MI and PI, significantly decreased AI and also attenuated hepatic vacuolar degeneration and sinusoidal congestion in PH rats. UD treatment significantly decreased the elevated tissue MDA level and increased the reduced SOD activity and GSH level in the tissues. These results suggest that UD pretreatment was beneficial for rat liver regeneration after partial hepatectomy.

Cyclosporin A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity, hypertension, and hepatotoxicity. Curcumin has been successfully used as a potent antioxidant against many pathophysiological states. This experimental study was performed to test, during CsA treatment, the alterations of curcumin antioxidant properties against CsA-induced endothelial dysfunction. Rats were divided into four groups: control, curcumin alone, CsA, and CsA + curcumin; each group containing eight animals. The animals in the CsA + curcumin group were treated with CsA (10 days, 25 mg/kg, orally) and curcumin (15 days, 200 mg/kg, orally, starting 5 days before CsA administration). At the end of the treatments, the animals were killed; serum and aorta tissue were treated for biochemical and morphological analyses. The results indicate that CsA-induced aortic endothelial dysfunction was characterized by morphological and ultrastructural alterations in tissue architecture, changes in malondialdehyde and ferric reducing/antioxidant power levels, and increase in endothelial nitric oxide synthase and terminal-deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) expression. In conclusion, our data suggest that the imbalance between production of free oxygen radicals and antioxidant defence systems, due to CsA administration, is a mechanism responsible for oxidative stress. Moreover, we show that curcumin plays a protective action against CsA-induced endothelial dysfunction and oxidative stress, as supported by biochemical, ultrastructural, immunohistochemical, and TUNEL results.