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Sitagliptin increases the levels of incretin hormones and stimulates a decrease in blood glucose levels, by blocking the DPP4 enzyme. We have very limited information about impact of sitagliptin on male genital system and relationship between sitagliptin/diabetes/ER. Fucoidan can be effective in blood glucose homeostasis. We goal to explain of the effect of sitagliptin and introduce an approach of fucoidan treatment in experimental diabetes in male rats. Fifty-eight Wistar albino rats were divided into C-control group and D-diabetes group: 60 mg/kg streptozotocin intraperitoneal (i.p.); DS group: STZ + 10 mg/kg sitagliptin intragastric (i.g.); DF group: STZ + 100 mg/kg fucoidan i.p.; and DSF group: STZ + 10 mg/kg sitagliptin + 100 mg/kg fucoidan. A significant decrease was detected when DS, DF and DSF groups compared to group D in blood glucose levels, basement membrane thickness and also apoptotic cell/tubule index, pJNK, caspase 3, caspase 12, GRP78, CHOP and DPP4. Sitagliptin and fucoidan have been found to be effective in blood glucose homeostasis and reducing the expression of certain proteins that lead to apoptosis and especially the proteins in the ER stress pathway. Therefore, we think that both sitagliptin and fucoidan can be effective in preventing or eliminating histopathological damages in diabetic testicular tissues, and their treatment effects can be used more.

After burns, protecting tissues by medicines in the zone of stasis reduces the width and depth of injury. This study's goal was to reduce burned tissue damage in the zone of stasis using epidermal growth factor (EGF). Forty-eight Wistar rats were separated into three groups. In all groups, the burn procedure was applied following the comb burn model. In Group 1, no postburn treatment was administered. In Group 2, physiological saline solution (0.3 cc) was injected intradermally and in Group 3, EGF (0.3 cc) was injected intradermally into stasis zone tissues after the burn procedure. Surviving tissue rates were 24.0% in Group 1, 25.3% in Group 2, and 70.2% in Group 3. The average numbers of cells stained with Nrf2, HO-1, and the number of apoptotic cells were 230, 150, and 17.5 in Group 1, 230, 145, and 15.0 in Group 2, and 370, 230, and 0 in Group 3, respectively. Values in Group 3 were found to be statistically significantly different than those of Groups 1 and 2; there was no difference between Groups 1 and 2. This study shows that EGF protects zone of stasis tissue from burn damage.

Objective: In burn injury, the zone of stasis determines the width and depth of the necrosis. Our aim is to show the effectiveness of quercetin on the viability within the zone of stasis in burns of rats. Materials and Methods: Forty-eight rats were divided into three groups. The rats in Group 1 (control group) were only applied the comb burn model; the rats in Group 2 (post-burn group) were administered 50 mg/kg of quercetin intraperitoneally, every day after the burn procedure until euthanasia; and the rats in Group 3 (pre-burn group) were administered 50 mg/kg of quercetin intraperitoneally, every day for 7 days before and after the burn procedure until euthanasia. Results: The living tissue calculated was 85.41% (+/- 14.06) in Group 3, 40.37% (+/- 9.75) in Group 2, and 16.81% (+/- 9.4) in Group 1. The level of apoptosis was 30.0 (+/- 10.8) in Group 3, 33.8 (+/- 08.7) in Group 2, and 37.4 (+/- 11.5) in Group 1. The level of autophagy was 49.50 (+/- 8.58) in Group 3, 27.17 (+/- 5.53) in Group 2, and 21.00 (+/- 5.66) in Group 1. All the differences between the groups were statistically significant (p< 0.01). Conclusion: Quercetin reduces apoptosis and increases autophagy, thereby increasing tissue viability in the zone of stasis of burn injury. Namik Kemal University Research Center [NKUBAP.00.20.AR.15.01] The article was supported under project NKUBAP.00.20.AR.15.01 by the Namik Kemal University Research Center.

We investigated the morphologic and molecular effects of exposure to cadmium (Cd) for 30 and 60 days on the uteri of mice. We assessed uterine morphometric measurements, eosinophilia, mast cell numbers, endometrial apoptosis, proliferation and estrogen receptor alpha (ERα) immunoreactivity. We examined vaginal smears that reflected the hormonal alterations in the female reproductive tract. Because the female reproductive tract exhibits different morphology at each stage of the estrous cycle, we sacrificed all animals at estrus to make appropriate comparisons. Female BALB/c mice were exposed to 200 ppm Cd in their drinking water for either 30 or 60 days. Cd exposure caused significant decreases in endometrial thickness and number of glands in estrus phase uteri. The endometrial eosinophilia in the groups exposed to Cd also decreased compared to controls. Cd exposure increased the number of mast cells. Luminal and glandular epithelia were examined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and by immunostaining proliferating cell nuclear antigen (PCNA) and estrogen receptor α (ERα). Compared to controls, the apoptotic index increased with time in both Cd exposed groups, while the proliferation index decreased. ERα immunoreactivity was decreased in both Cd exposed groups compared to controls; the decrease was most apparent in the 30 day Cd group. We found that 60 day Cd exposure increased apoptosis in the endometrium, which may affect the receptivity of the uterus for implantation.

The aim of this study was to evaluate the role of vitamin E in follicular degeneration and to assess histopathological and biochemical changes following ischemia-reperfusion (IR) injury in rat ovaries. Twenty-eight Wistar albino rats were randomly divided into four groups: sham, 4. h torsion, 24. h detorsion, and a vitamin E group. Thirty minutes before detorsion, a single dose of 200. mg/kg vitamin E was administered intraperitoneally. The ovarian histology score was determined, serum levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. The apoptosis of granulosa cells and the phospho-c-jun N-terminal kinase (p-JNK) and phospho-p38 (p-p38) immunoreactivities of these cells were determined. MDA and MPO levels were significantly increased in the torsion and detorsion groups. Hemorrhage, edema, and congestion were also apparent in these groups. In addition, the apoptotic index and the immunoreactivity of p-JNK were highest in the detorsion group, which also showed marked follicular degeneration. However, p-p38 activity was not affected by torsion-detorsion (TD) induction. Vitamin E ameliorated TD-induced histological alterations. It also decreased serum levels of MDA and MPO, reduced the activity of p-JNK in the ovaries, and reduced numbers of apoptotic follicular cells. In conclusion, these data indicate that vitamin E attenuated ovarian follicular degeneration by inhibiting the immunoreactivity of p-JNK and reducing the apoptosis of granulosa cells. © 2013 Elsevier Inc., 2011-121, The authors acknowledge Trakya University Research Center, Edirne, Turkey for the financial support (project no: 2011-121 ).

Background This study evaluated the protective effect of sildenafil on liver injury induced by intestinal ischemia-reperfusion. Methods Forty female Sprague Dawley rats were divided into 4 groups: sham-control (SC), ischemia (I), ischemia-reperfusion (IR), and ischemia-reperfusion + sildenafil (SIL; sildenafil gavaged at 50 mg/kg before operating). A 2-h ischemia-reperfusion was performed by clamping the superior mesenteric artery. Liver function, plasma alanine (ALT) and aspartate (AST) aminotransferase, and intestinal and liver malondialdehyde (MDA) were measured at the end of the experiment. Intestinal and liver tissue damage was examined by histology. Liver samples were immunologically stained for endothelial nitric oxide synthase (eNOS) and proliferating cell nuclear antigen (PCNA). Results The ALT and AST levels were highest in the IR group and were lower in the SIL group (p < 0.05). Intestinal MDA levels were statistically higher in the IR group than in the SC, I and SIL groups. Liver MDA levels were significantly higher in the IR group than in the I and SC groups (p < 0.05) and higher than in the SIL group (p > 0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p < 0.05). Sildenafil reduced damage and also increased eNOS and PCNA immunoreactivity in liver tissue. Conclusions Sildenafil shows a protective effect on intestinal ischemia-reperfusion-induced liver injury, possibly by decreasing vascular resistance through increased nitric oxide levels. © 2013 Elsevier Inc.

We investigated the role of the Fas/Fas ligand (FasL) signaling pathway in diabetic male infertility. Male rats were divided into two groups: a control group and a streptozotocin induced diabetic group. Thirty days after induction of diabetes, samples of testes were harvested and fixed in 10% formalin for light microscopy. Germ cell apoptosis was determined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) and immunostaining of caspase 8 and active caspase 3. We also investigated the expressions of Fas and FasL using immunohistochemistry. Streptozotocin-induced diabetes caused severe histopathological damage and increased apoptotic tubule and apoptotic cell indices, caspase 8 and caspase 3 expressions, and Fas and FasL-immunopositive cells in the rat testes. We suggest that the Fas/FasL signaling pathway may play a role in male infertility caused by diabetes.

This study evaluated the possible effects of flaxseed oil on renal damage associated with hyperlipidaemic rats. Wistar albino male rats were divided into three groups. Group I was fed with a pellet chow. Group II was fed with a high cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added to the pellet chow. Group III was fed with the same HCD, but were orally treated with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started 1 week before and continued throughout the 22 weeks of the HCD. At the end of the experiment, renal tissue and blood samples were collected. The biochemical and histopathological findings confirmed renal damage in hypercholesterolaemia conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed that lowered serum lipid was accompanied by a decreased deposition of neutral lipid. Flaxseed oil effectively reversed these abnormalities, verifying the protective effects of flaxseed oil in ameliorating renal injuries associated with hypercholesterolaemia.

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.

The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion + NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150 mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis. © 2014 Springer Science+Business Media., 2012-90, Acknowledgments This study is supported by Trakya University Research Center, Edirne, Turkey, financially (Project No: 2012-90).

The present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid. Rats were randomly divided into three groups: control, acetic acid, and acetic acid+curcumin. Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days. Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls. In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis. Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis. Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats. The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38- and JNK-MAPK pathways. © Mary Ann Liebert, Inc.

Purpose: In this study, we tested the effects of L-carnitine (LC) on radiation-induced ileal mucosal damage. Materials and methods: Thirty Wistar albino rats were divided into five groups. The control group received physiological saline intraperitoneally (i.p.). Radiation-1 and radiation-2 groups received whole-body X-irradiation of 8.3 Gy as a single dose. These groups were sacrificed at the 6th hour and 4th day after irradiation, respectively. The Radiation-1 + LC and the radiation-2 + LC groups received the same dose irradiation plus a daily dose of 200 mg/kg LC. LC was applied one day before and for four days after irradiation. Results: The levels of serum monocyte chemotactic protein-1 (MCP-1) and interferon gamma (IFN-?) were significantly higher in the radiation groups when compared with the control. Treatment with LC decreased the serum MCP-1 and IFN-? levels considerably. In the radiations groups, the Chiu score was significantly elevated compared with that of the control group. However, LC administered prior to the irradiation reduced the severity of mucosal damage. The number of apoptotic cells of the ileal crypt in the irradiated rats increased from the 6th hour after irradiation and then decreased at 4th day. Conclusions: Our data demonstrated that LC may be beneficial to radiation enteritis. © 2013 Informa UK, Ltd.

The present study was performed to determine the effect of amifostine in the prevention of radiation-induced acute and late period morphologic damages in rat kidney via light and electron microscopic examinations.Control rats (n=6) received saline solution 30 min before sham irradiation; the radiotherapy alone group (n=12) received saline solution 30 min before irradiation (a single dose of 15 Gy, applied unilaterally to the kidney) and a final radiotherapy +amifostine group (n=12) received 200 mg/kg amifostine 30 min prior to irradiation.Microscopic examinations of irradiated kidneys revealed presence of glomerular tuft capsular adhesion, fusion of the foot processes and ballon-like cellular degeneration and loss of luminal brush border in tubules as early as eight weeks after irradiation. By 24 weeks post-irradiation, these changes were advanced and associated with focal mesangiolysis, segmental sclerosis and focal tubular atrophy. In addition, local irradiation caused interstitial fibrotic lesions in the kidney. Pretreatment of amifostine markedly prevented these glomerular and tubular changes, and interstitial fibrotic lesions.This study suggests that amifostine pretreatment may contribute to prevention of radiation-induced acute and late nephrotoxicity.

This study evaluated the possible effects of flaxseed oil on renal damage associated with hyperlipidaemic rats. Wistar albino male rats were divided into three groups. Group I was fed with a pellet chow. Group II was fed with a high cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added to the pellet chow. Group III was fed with the same HCD, but were orally treated with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started 1 week before and continued throughout the 22 weeks of the HCD. At the end of the experiment, renal tissue and blood samples were collected. The biochemical and histopathological findings confirmed renal damage in hypercholesterolaemia conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed that lowered serum lipid was accompanied by a decreased deposition of neutral lipid. Flaxseed oil effectively reversed these abnormalities, verifying the protective effects of flaxseed oil in ameliorating renal injuries associated with hypercholesterolaemia.

The present study, we hypothesized that L-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (gamma)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + L-carnitine group received scrotal gamma-irradiation plus 200 mg/kg i.p. L-carnitine. L-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of gamma-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, L-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy.