Therapeutic effects of melatonin in long-term exposure to 2100MHz radiofrequency radiation on rat sperm characteristics.

INTRODUCTION: Radiofrequency electromagnetic fields (RF-EMFs) are one of the risk factors for male reproductive health and melatonin can be an ideal candidate for therapeutic development against RF-induced male fertility problems due to its antioxidant properties. The possible therapeutic role of melatonin in the destructive effects of 2100MHz RF radiation on rat sperm characteristics is investigated in the present study. METHODS: Wistar albino rats were divided into four groups and the experiment continued for ninety consecutive days; Control, Melatonin (10mg/kg, subcutaneously), RF (2100MHz, thirty minutes per day, whole-body), and RF+Melatonin groups. Left caudal epididymis and ductus deferens tissues were placed in sperm wash solution (at 37°C) and dissected. The sperms were counted and stained. Measurements of the perinuclear ring of the manchette and posterior portion of the nucleus (ARC) were performed and the sperms were examined at an ultrastructural level. All of the parameters were evaluated statistically. RESULTS: The percentages of abnormal sperm morphology were significantly increased with RF exposure, while the total sperm count was significantly decreased. RF exposure also showed harmful effects on acrosome, axoneme, mitochondrial sheath, and outer dense fibers at the ultrastructural level. The number of total sperms, sperms with normal morphology increased, and ultrastructural appearance returned to normal by melatonin administration. DISCUSSION: The data showed that melatonin may be a beneficial therapeutic agent for long-term exposure of 2100MHz RF radiation-related reproductive impairments.

The effect of di-n-butyl phthalate on testis and the potential protective effects of resveratrol.

This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di-n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.

Biochemical and histopathological effects of catechin on experimental peripheral nerve injuries.

AIM: Catechin is a type of polyphenol, along with epicatechin, epigallocatechin, and epigallocatechin-gallate (EGCG). This study aims to investigate the effect of EGCG, a major metabolite of catechin, which is the principle bioactive compound in green tea, on rats with peripheral nerve injury. MATERIAL AND METHODS: A total of 74 rats were divided into six groups, namely the control, the trauma, the normal saline, a 25mg/kg EGCG, a 50mg/kg EGCG and a daily consumption group (10mg/kg EGCG was given intraperitoneally for 14 days before the trauma). Except the first group, the other groups underwent a 1-minute sciatic nerve compression by clip with 50gr/cm2 pressure. Nerve samples were obtained at 28 day after trauma for the biochemical and histopathological analysis. RESULTS: Our study showed that the Daily consumption, 25mg/kg EGCG and 50mg/kg EGCG groups demonstrated statistically significant decreased lipid peroxidation levels and particularly daily consumption, and the 25mg/kg EGCG group showed a favourable reduction of degeneration and edema histologically. CONCLUSION: This study shows that Catechin and its derivatives have a protective effect on peripheral nerve injury.

The neuroprotective effects of rituximab in rat spinal cord injury model: an immunohistochemical study.

AIM: In the present study, we investigate the neuroprotective effects of rituximab, a monoclonal antibody directed towards B cell mediated humoral immunity, on a rat spinal cord injury (SCI) model with immunohistochemical methods. MATERIAL AND METHODS: Twenty-four rats were used for the study. Rats were divided as control, SCI, and rituximab-treated SCI groups. Intraperitoneal rituximab administration was performed on days 0, 3 and 5 in the third group. Rats were sacrificed 7 days after trauma. Antibodies against IL-1ß, IL-6, TNF-α and CD20 were studied with the ELISA method together with electron microscopic analysis. RESULTS: It was found that rituximab suppressed oligodendrocytes at the phagocytic stage but was still inefficient for the regenerative phase. TNF-α expression was markedly increased in rats subjected to SCI and suppressed after rituximab treatment. Decreased CD20 expression was another prominent finding in rats under rituximab therapy. However, expressions of IL-1ß and IL-6 were both increased in glial cells without significant change after rituximab administration. CONCLUSION: TNF-α expression was augmented at the level of SCI both in neuronal and glial cells, particularly in oligodendrocytes. All were suppressed after rituximab administration and rituximab reduced CD20 expression both in neuronal and supportive glial cells which may be related to neural healing.

Tobacco-induced neuronal degeneration via cotinine in rats subjected to experimental spinal cord injury.

OBJECTIVES: Cigarette smoke contains over 4000 chemicals including well-characterized toxicants and carcinogens, among which is cotinine. Cotinine is the principal metabolite of nicotine that has adverse affects on the microcirculation via vasoconstriction, hypoxia and the wound-healing cascade. Its impact on spinal cord injury (SCI) has not been investigated yet. The aim of the present study is to investigate the cotinine effect on SCI. METHODS: 48 male Wistar rats were divided into six groups as follows: sham-control, sham-trauma, vehicle-control, vehicle-trauma, cotinine-control, and cotinine-trauma. Initially, a defined concentration of cotinine blood level was maintained by daily intraperitoneal injection of cotinine for 14 days in the cotinine groups. The concentration was similar to the cotinine dose in the blood level of heavy smokers. Only ethyl alcohol was injected in the vehicle groups during the same period. Then, SCI was performed by a Tator clip. The cotinine groups were compared with rats subjected to vehicle and sham groups by immunohistochemical biomarkers such as glial fibrillary acidic protein (GFAP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP) expressions. Electron microscopic examination was also performed. RESULTS: GFAP-positive cells were noted to be localized around degenerated astrocytes. Marked vacuolization with perivascular and perineural edema was seen in the cotinin consumption groups. These findings showed the inhibition of regeneration after SCI. Similarly, vacuolization within myelin layers was noted in the cotinine groups, which was detected through reduced CNP expression. CONCLUSION: Cotinine, a main metabolite of nicotine, has harmful effects on SCI via GFAP and CNP expression. The findings of the present study support the hypothesis that tobacco causes neuronal degeneration via cotinine.

Bacterial biofilm formation in the middle-ear mucosa of chronic otitis media patients.

Biofilm formation is present in the middle-ear mucosa of chronic otitis media (COM) patients and COM is a biofilm-related disease. Biofilms are organized and complex communities in which bacteria communicate to each other and gain tremendous advantages. In this unique structure, bacteria can diffuse nutrients, gain resistance to antimicrobials agents and host defense mechanisms. Recently bacterial biofilms have been proven to be important in infectious diseases of head and neck region. A prospective case-control study was conducted. The study group comprised of patients with chronic otitis media and patients undergoing surgery for cochlear implantation was involved in the control group. Study group also divided to subgroups SSA and SSB according to history of ear discharge within last six months. Direct microscopy (DM) and transmission electron microscopy (TEM) were used to assess presence of biofilms. Totally 19 patients, 10 with ear discharge history within last 6 months and 9 without discharge comprised the study group. Control group comprised of 9 patients undergone cochlear implantation. In all of the patients with ear discharge history and in two of the patients without ear discharge history, biofilm formation was detected by both DM and TEM. All control group members were free of biofilm formation. The differences were statistically significant between study and control groups (p = 0.002) and between study subgroups (p < 0.001); but not significant between study subgroup without ear discharge history and control group (p = 0.470). In the middle ear mucosa of patients with chronic otitis media, biofilm formation is common, especially when ear discharge history is present.

The morphological evaluation of ipsilateral and contralateral vasa deferentia in a rat model of unilateral spermatic cord torsion.

AIM: Spermatic cord torsion is a surgical emergency that requires early intervention to protect the effected testicle. The literature review about this ischemic reperfusion (I/R) injury reveals not only ipsilateral, but also contralateral testicular and epididymal injuries in a broad fashion. However, there is no data about vas deferens injury related with this surgical emergency. The aim of the study is to evaluate the morphological changes of the vas deferens due to testicular I/R injury. MATERIALS AND METHODS: Eighteen Wistar-Albino rats were allocated to three groups. Bilateral vasa deferentia of control group (Gr C, n = 6) were harvested without any surgical intervention. The torsion group was subjected to 2 h torsion and 2 h detorsion of the left testicle (Gr T, n = 6) and the third group underwent sham operations (Gr S, n = 6). Bilateral vasa deferentia of Gr T and S were harvested after surgery. The either side of the vas deferens was divided into three equal segments and these regions (adjacent to urinary bladder, medial and adjacent to testicle) were evaluated histopathologically. RESULTS: The electron microscopic evaluation of bilateral vasa deferentia of Gr T revealed different degrees of degeneration on either side. The region adjacent to testicle of the contralateral vas deferens was the most effected segment when compared with the other segments. CONCLUSION: In the light of these findings, it can be said that testicular I/R injury effects not only testis and epididymis, but also the adjacent vas deferens. This effect seems to be bilateral, like the testis and epididymis injury. Moreover, it mostly seems to depend on the apoptotic processes.

Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells.

PURPOSE: To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells. METHODS: Fifty-six female prepubertal Wistar rats (21-24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques. RESULTS: In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 +/- 1.32 in controls, and significantly increased to 29.60 +/- 1.58, 34.20 +/- 2.53, and 54.80 +/- 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group. CONCLUSION: VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.

High dose cotinine may induce neural tube defects in a chick embryo model.

AIM: Nicotine is a well-known agent among 4000 chemicals in cigarettes. About 70 to 80% of nicotine is converted to cotinine, a major metabolite. The aim of the present study is to investigate the effect of cotinine on neural tube development in a chick embryo model. MATERIAL AND METHODS: Sixty fertile, specific pathogen free eggs were divided into 6 groups for this study. In the first group, a fixed cotinine concentration for each egg was calculated just to simulate the concentration of a smoker's blood level. A second experimental group was designed at a higher cotinine concentration. Embryos that succeeded to reach Hamburger-Hamilton stage 12 from each group were then embedded into paraffin for permanent sections. These two groups were compared with eggs subjected to vehicle (standard alcohol and ten times more alcohol concentration) and control groups (saline and sham groups). RESULTS: Embryos of the cotinine (regular dose), vehicle and control groups were normal, but embryos subjected to higher cotinine concentrations were malformed at the cranial part of the thoracic neural tube. CONCLUSION: Association of cotinine with neural tube defects was demonstrated in the present study. Cigarette smoking may induce hazardous effects on neural tube development.

Effects of metformin on mammalian target of rapamycin in a mouse model of endometrial hyperplasia.

OBJECTIVE: The effects of metformin on S6K1, which is a crucial effector of mTOR signaling, and on endometrium were studied in a mouse model of endometrial hyperplasia induced by unopposed estradiol or tamoxifen. STUDY DESIGN: Forty-eight oophorectomized Balb/c mice were randomly assigned to receive saline, tamoxifen citrate (4 mg/kg), 17-beta estradiol hemihydrate (4 mg/kg), metformin (50 mg/kg), tamoxifen citrate (4 mg/kg) with metformin (50 mg/kg), or estradiol (4 mg/kg) with metformin (50 mg/kg) for 3 days. Histological markers of uterotrophy, including luminal epithelial cell height and density of endometrial glands were quantified for each slide. Immunohistochemical expression of PCNA and S6K1 was evaluated. H-score was used for S6K1 expression. Statistical analysis was performed using Student's t-test for comparison of two continous variables and one-way ANOVA for comparison of multiple variables. RESULTS: Mice treated either with tamoxifen or estradiol had significantly increased density of endometrial glands and epithelial heights compared to vehicle-only or metformin-only group (p<0.001). Addition of metformin to tamoxifen or estradiol treated mice significantly decreased the density of endometrial glands and epithelial cell heights (p<0.05). Addition of metformin to tamoxifen significantly decreased the H-score of S6K1 (p<0.05) and the immunohistochemical expression of PCNA (p<0.05) in uterine lining epithelium, glandular and stromal cells. Addition of metformin to estradiol significantly decreased the H-score of S6K1 (p<0.05) and the immunohistochemical expression of PCNA (p<0.05) in uterine lining epithelium, glandular and stromal cells. CONCLUSION: Metformin seems to have possible antiproliferative effects on the endometrium of estradiol or tamoxifen treated mice via inhibiting the mTOR mediated S6K1 activation.

RAD001 (Everolimus) Can prevent tamoxifen-related endometrial and stromal hyperplasia.

The mechanism of tamoxifen-associated endometrial hyperplasia and cancer is not elicited. RAD001 inhibits a target protein in phosphatidyl kinase pathway, which is involved in endometrial hyperplasia and cancer. We investigated whether endometrial hyperplasia can be prevented through inhibition of the target of rapamycin by RAD001. Sixty BALB/c mice underwent oophorectomy and were divided into 6 groups: group 1, placebo group; group 2, tamoxifen-treated (4 mg/kg per 24 hours); group 3, estradiol-treated (4 mg/kg per 24 hours); group 4, RAD001-treated (1.5 mg/kg per 24 hours); group 5, tamoxifen (4 mg/kg per 24 hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated; and group 6, estradiol (4 mg/kg per 24 hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated. The count of glands, the length of epithelium, and immunohistochemical staining of proliferating cell nuclear antigen were analyzed. The count of total glands and the epithelial length were 30.8 (7.1) and 126 (43.4) microm, 53 (8.1) and 162.5 (34.8) microm, 65.2 (13.6) and 401.4 (44.0) microm, and 82.0 (5.2) and 444.7 (57.8) microm in the placebo-, the RAD001-, the tamoxifen-, and the estradiol-treated groups, respectively (P < 0.05). Although addition of RAD001 to estradiol did not decrease the count of total glands and the epithelial length, addition of RAD001 to tamoxifen did (43.3 [13.3] and 218.0 [29.2] microm, P < 0.05). The immunoreactive score of proliferating cell nuclear antigen is significantly decreased by the addition of RAD001 to either tamoxifen or estradiol in the epithelial and glandular cells. RAD001 can prevent tamoxifen-associated and estrogen-related endometrial hyperplasias in mice. RAD001 also decreases stromal cell proliferation in the tamoxifen-treated mice.

Continuous or intermittent noise exposure, does it cause vestibular damage? An experimental study.

OBJECTIVE: Aim of this study was to compare vestibular changes in guinea pigs exposed to same level of continuous and intermittent noise by electron microscopy. METHODS: The study included 10 adult albino guinea pigs. In a silent room, a 4-kHz octave band noise at an intensity of 120 dB SPL was presented. Six animals were exposed to continuous noise for 6h, and four animals were exposed to 12h intermittent noise. One day after noise exposure eight guinea pigs were decapitated and temporal bones of one side were removed. Ten days after continuous noise exposure two guinea pigs were decapitated. They were examined with an electron microscope. RESULTS: The most characteristic changes in the macula of the continuous noise exposure group were degeneration of the epithelial cells and separation in their layers. Marked crystolysis and stromal cell apoptosis were also noted in this group compared to the intermittent noise exposure group. Effect of noise was more obvious in the group that continuous noise was applied. The histological changes in group which examined after 10 days were similar to the group that examined after 1 day. CONCLUSION: Continuous noise can cause more damage to the vestibular system compared with intermittent noise and histological changes after continuous noise are permanent.

Ultrastructural damage in lung tissues in rats treated with doxorubicin and paclitaxel.

INTRODUCTION: The aim of this study was to determine the ultrastructural effects of doxorubicin (Adriblastina; Pharmacia and Upjohn, Milan, Italy), paclitaxel (Taxol; BMS, Princeton, NJ), Cremophor EL (a diluent of paclitaxel) and doxorubicin/paclitaxel combinations on normal lung tissues. METHODS: In the experimental protocol, 50 Wistar albino rats were used, divided into five different groups: the control group (n=10), the doxorubicin group (1 mg/kg) (n=10), the paclitaxel group (2 mg/kg) (n=10), the Cremophor EL group (150 mg/kg) (n=10) and the paclitaxel/doxorubicin group (2 mg/kg+ 1 mg/kg) (n=10). The drugs were administered weekly to rats via intraperitoneal injections for 14 weeks. After 3 weeks of observation, the rats were killed with thiopental sodium (30 mg/kg) and their left median lung tissues were removed and examined with a Carl Zeiss EM 900 transmission electron microscope. RESULTS: Our experiments showed doxorubicin to cause an increase in collagen fibre content of the alveolar wall, and paclitaxel to cause degenerations in cellular organelles. In the group in which the two agents were administered together, both effects were observed, although the effects of paclitaxel were seen to be dominant. Ultrastructural appearance was similar in the Cremophor EL group compared to the control group. CONCLUSION: It was detected that doxorubicin and paclitaxel caused ultrastructural degenerations in normal lung tissues and Cremophor EL seemed to be unaccountable for these degenerations.

Angiotensin II captopril cotreatment augments angiogenesis in abdominal skin flap in rats.

The effect of captopril, angiotensin-converting enzyme inhibitor, on angiogenesis in several reports remained unclear. Its effect on neovascularization in rat abdominal skin flaps was investigated. Flap elevation, based on the right superficial inferior epigastric artery was performed with or without the administration of captopril (10 mg/kg/d), Ang II (100 microg/kg/d), or captopril and Ang II cotreatment. Mean arterial pressure (MAP), microangiography, capillary density measurement, necrosis area determination, laser Doppler flowmetry (LDF), AT1 and vascular endothelial growth factor (VEGF) immunostaining were used to evaluate the effects of captopril and the interaction between captopril and Ang II on the angiogenesis. Ang II and captopril cotreatment improved angiogenesis more than Ang II or captopril alone. The reduction of necrosis, enhancement of vascular network formation, capillary density, VEGF immunostaining, and local blood flow were evident in the cotreated group. We suggest that Ang II and captopril cotreatment improves ischemia-induced angiogenesis and increased viability and vascularity of skin flap in rats.

Effects of taurine in cellular responses to oxidative stress in young and middle-aged rat liver.

Aging is related with an increased cellular level of lipid peroxides and reactive oxygen species (ROS). The useful effects of taurine as an antioxidant in biological systems have been attributed to its capability to stabilize biomembranes, to scavenge ROS, and to decrease the peroxidation of unsaturated membrane lipids. The aim of the present study was to investigate the effects of taurine on malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), thioredoxin reductase (TR), and endothelial nitric oxide synthase (eNOS) in young and middle-aged rat liver. There was not a significant difference in liver MDA levels between the control groups of young and middle-aged rats (P > 0.05). However, liver GSH levels, and GPx and TR activities between the control groups of young and middle-aged rats were significantly different (P < 0.05). Liver MDA level was significantly lower in the taurine group of middle-aged rats (P < 0.05). Liver GSH levels, and GPx and TR activities were significantly increased in the taurine group of middle-aged rats when compared to the control group (P < 0.05). Liver MDA level was significantly lower in the taurine group of young rats than the ones in the control group (P < 0.05). Liver TR activity was significantly increased in the taurine group of young rats when compared to the control group (P < 0.05). Liver GPx activity was not statistically different between the taurine and the control groups in young rats (P > 0.05). Liver GSH levels were not different between the young taurine and the control groups (P > 0.05). Immunohistochemical studies exhibited no change in eNOS activity after taurine injection in young rats. However, in middle-aged rats, taurine lowered the eNOS reactivity to the same level found in young rats. These results suggested that exogenous taurine might play a role in aging by means of its reducing effects on free radical levels in parallel to an increase in the antioxidant capacity.

Effect of fluoride intoxication on endometrial apoptosis and lipid peroxidation in rats: role of vitamins E and C.

Fluoride is a strong, hard anion and cumulative toxic agent. The effect of fluoride intoxication on lipid peroxidation in endometrial tissue and the protective effects of combinations of vitamins E and C in rats were studied. Additionally, the apoptotic changes in endometrial tissue were examined. Experimental groups were as follows: control group; a group treated with 100 mg/l fluoride (F group); and a group treated with 100 mg/l fluoride plus vitamins E and C (F+Vit group). The F and F+Vit groups were treated orally with fluoride for 30 days. Vitamins E and C were injected simultaneously at doses of 50 mg/kg day i.m. and 20 mg/kg day body weight i.p. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick and labeling (TUNEL) method. Malondialdehyde (MDA) levels were determined in uterine tissue of rats. Fluoride caused a significant increase in MDA levels (an important marker of lipid peroxidation) in the fluoride group compared with the controls (p<0.05). Vitamins E and C significantly reduced the fluoride-induced lipid peroxidation in the F+Vit group compared with the F group (p<0.05). Diffuse apoptosis in glandular epithelium and stromal cells was found in endometrial tissues of F treated rats by TUNEL method. The severity of these lesions was reduced by the administration of vitamins. From these results, it can be concluded that subchronic fluoride administration causes endometrial apoptosis, and lipid peroxidation may be a molecular mechanism involved in fluoride-induced toxicity. Furthermore, treatment with a combination of vitamins E and C reduced endometrial apoptosis caused by fluoride.

Endometrial damage and apoptosis in rats induced by dichlorvos and ameliorating effect of antioxidant vitamins E and C.

We aimed to investigate the effect of subchronic administration of dichlorvos (DDVP) on endometrium and to evaluate ameliorating effects of a combination of Vitamins E and C against DDVP toxicity in the rat. Three groups of rats were used in the experiment. The first group was treated with 4 mg/kg DDVP; the second group was treated with 4 mg/kg body weight DDVP plus Vitamins E and C (DDVP+Vit); the third group was given only corn oil (control). DDVP and DDVP+Vit groups were given DDVP by gavage 5 days a week for 4 weeks at a dose level of 4 mg/kg day by using corn oil as the vechicle. Vitamins E and C were injected at doses of 50 mg/kg i.m. and 20 mg/kg body weight i.p. Histopathological and immunohistochemical examinations for caspase-3 and caspase-9 were accomplished in the endometrium. The level of malondialdehyde (MDA) increased significantly in the DDVP group compared with the control group (p<0.05). MDA significantly decreased in the DDVP+Vit group compared with the DDVP group (p<0.05). Administration of Vitamins E and C along with DDVP significantly reduced the histopathological changes and the extent of apoptosis. In conclusion, subchronic DDVP administration caused endometrial damage and that treatment with a combination of Vitamins E and C reduced endometrial damage caused by DDVP.

[The effects of early intermittent high-dose estrogen treatment on bone structure of ovariectomized rats]. / Ooferektomi yapilmis siçanlarda aralikli yüksek doz östrojen tedavisinin kemik yapisi üzerine etkisi.

OBJECTIVES: The effects of various estrogen replacement protocols to prevent bone loss following ovariectomy have been the subject of many studies in rats. This study was designed to determine the effects of early intermittent high-dose estrogen replacement therapy, which has hitherto not been studied, on bone structure of ovariectomized rats. METHODS: Bilateral ovariectomies were performed in 20 female mature non-pregnant Wistar rats. All the animals were randomly assigned to two groups to receive either subcutaneous 17 beta-estradiol (25 mg/kg) or only sesame oil on days 15 and 22 after ovariectomy. Fourteen days after the last injection, the rats were sacrificed and proximal femurs were removed for both light and electron microscopic analyses. RESULTS: In the light microscopic analysis, control femurs exhibited a marked destruction in the structure of the cancellous bone, whereas estradiol-treated rats had almost normal cancellous bone. Ultrastructural analysis showed degeneration and increased turnover in bone cells of the control femurs, whereas the bone cells and the bone matrix appeared almost normal in the treatment group. A statistically significant increase in serum estrogen levels was found in estradiol-treated rats (580+/-124 pg/ml versus 62+/-16 pg/ml, p<0.001). CONCLUSION: Intermittent high-dose estrogen treatment prevents cancellous bone loss in the proximal femurs of ovariectomized rats through inhibition of bone turnover and results in significantly increased serum estrogen levels.