Publications by authors named "Osman Nuri Keles"

26 Publications

  • Page 1 of 1

Effect of Titanium Dioxide and Silver Nanoparticles on Mitochondrial Dynamics in Mouse Testis Tissue.

Biol Trace Elem Res 2021 Jun 8. Epub 2021 Jun 8.

Department of Molecular Biology and Genetics, Science Faculty, Ataturk University, Erzurum, Turkey.

This study was performed to investigate whether the toxicity of nanoparticles (Ag NPs or TiO NPs) affected mitochondrial dynamics (mitochondrial fusion and fission mechanisms) in testicular cells of mice. Animals were assigned into three groups (ten mice per group): control group (distilled water), TiO NP group (5 mg/kg per dose), and Ag NP group (5 mg/kg per dose). NPs were administered intravenously (via tail vein) to mice with 3-day intervals. To determine the possible toxic effect of NPs on mitochondrial dynamics, the expression levels of mitochondrial fission (Drp1)- and fusion (Mfn1, Mfn2, OPA1)-related genes were analyzed. The results showed that both Ag NPs and TiO NPs entered the testis via the blood-testis barier and accumulated in mouse testis tissue. Experiments showed that administration of Ag NPs neither alters testicular weight and testicular index nor causes significant toxic effect on sperm parameters. RT-PCR analysis demonstrated that Ag NP treatment did not disrupt mitochondrial dynamics in testicular cells. Conversely, administration of TiO NPs (anatase, < 25 nm) decreased the sperm motility and the percentages of sperms with swollen tail. Furthermore, RT-PCR and western blot analyses showed that TiO NPs disrupted mitochondrial dynamics by causing excess mitochondrial fission (excess expression of Drp1 gene and DRP1 protein). This is the first report on the toxicity of nanoparticles on mitochondrial dynamics (fusion and fission mechanisms) in testicular cells.
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http://dx.doi.org/10.1007/s12011-021-02763-6DOI Listing
June 2021

Effect of oleuropein against chemotherapy drug-induced histological changes, oxidative stress, and DNA damages in rat kidney injury.

J Food Drug Anal 2017 04 2;25(2):447-459. Epub 2016 Aug 2.

Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey.

Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection. After exposure to the chemotherapy agent and OLE, oxidative DNA damage was quantitated in the renal tissue of experimental animals by measuring the amount of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts. Malondialdehyde (MDA) level, total oxidative stress (TOS), and total antioxidant status (TAS) were assessed to determine the oxidative injury in kidney cells. The histology of the kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), Masson trichrome, and amyloid. In addition, the blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE) levels were established. Our experimental data showed that tissue 8-OHdG levels were significantly higher in the cisplatin group when compared to the control group. The glomerular cells were sensitive to cisplatin as tubular cells. In addition, treatment with cisplatin elevated the levels of BUN, UA, CRE, and TOS, but lowered the level of TAS compared to the control group. The OLE therapy modulated oxidative stress in order to restore normal kidney function and reduced the formation of 8-OHdG induced by cisplatin. Furthermore, the OLE treatment significantly reduced pathological findings in renal tissue. We demonstrate for the first time that OLE presents significant cytoprotective properties against cisplatin-induced genotoxicity by restoring the antioxidant system of the renal tissue. According to our findings, OLE is a promising novel natural source for the prevention of serious kidney damage in current chemotherapies.
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http://dx.doi.org/10.1016/j.jfda.2016.07.002DOI Listing
April 2017

Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress.

Mediators Inflamm 2016 18;2016:9050828. Epub 2016 Feb 18.

Department of Cardiology, Faculty of Medicine, Erzincan University, Erzincan, Turkey.

Background: Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown.

Methods: Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days.

Results: We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p < 0.05).

Conclusion: Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.
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http://dx.doi.org/10.1155/2016/9050828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775802PMC
December 2016

Effects of Diabetes on Post-Menopausal Rat Submandibular Glands: A Histopathological and Stereological Examination.

Eurasian J Med 2015 Oct;47(3):199-207

Department of Histology and Embryology, Atatürk University Faculty of Medicine, Erzurum, Turkey.

Objective: The menopause in elderly women is a physiological process where ovarian and uterine cycles end. Diabetes means higher blood glucose level that is a metabolic disease and has an increased incidence. The aim of the study was to examine the single or combined effects of menopause and diabetes that causes pathophysiological processes on submandibular gland on ovariectomy and diabetes induced rat models.

Materials And Methods: Sprague Dawley twelve weeks old female (n=24) rats were divided randomly into four groups; Healthy control group (n=6), diabetic group (DM, n=6), ovariectomized group (OVX, n=6), post ovariectomy diabetes induced group (DM+OVX, n=6) individually. Histopathological, histochemical and stereological analyses were done in these groups.

Results: Significant neutrophil cell infiltrations and myoepithelial cell proliferations, granular duct and seromucous acini damages and changes in the content of especially seromucous acini secretion in DM and/or OVX groups and distinctive interstitial and striated duct damages in post ovariectomy diabetes induced group were detected. Alterations ingranular ducts hypertrophic and in seromucous acini atrophic were determined in DM and/or OVX groups.

Conclusion: The results revealed the pathophysiological processes that lead to morphological and functional alterations on the cellular level in submandibular glands. The molecular mechanisms related with pathogenesis of diabetes and menopause need further investigation.
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http://dx.doi.org/10.5152/eurasianjmed.2015.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659523PMC
October 2015

[Investigation of the protective effects of beta-D-glucan against invasive encapsulated Streptococcus pneumoniae sepsis in splenectomized rats].

Mikrobiyol Bul 2015 Jul;49(3):314-26

Ataturk University Faculty of Medicine, Department of Medical Microbiology, Erzurum, Turkey.

In asplenic individuals depending on the weakness of the immune response, sepsis are known to be developed with a high mortality rate. The most common species which are responsible for sepsis are encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Sepsis caused by immune deficiencies linked to splenectomy leads to infections particularly in the lungs and liver and causes multiple organ failure. On the other hand, -D-glucan (BDG), a branched glucose polymer, shows immunomodulatory activity, by enhancing the resistance of the host against microbial agents, and promotes phagocytic and proliferative activities of reticuloendothelial system. The aim of this experimental study was to investigate the effects of BDG alone and in combination with ceftriaxone on sepsis caused by encapsulated invasive S.pneumoniae serotype 19F. A total of 36 Sprague-Dawley rats were used in the study, and the animals (6 in each group) were equally divided into six groups as control, splenectomy, sepsis, BDG, ceftriaxone and BDG+ceftriaxone groups. Treatment groups were intravenously infected with S.pneumoniae 19F strain, and after sacrification, microbiological [bacterial counts (cfu/mL)], biochemical (myeloperoxidase activity, DNA oxidation, specific IgM and IgG levels) and histopathological analysis were performed in the tissue samples. In the study, BDG, ceftriaxone and BDG+ceftriaxone groups had statistically significant decrease in the amount of bacteria in all tissues when compared to the sepsis group (p<0.05). We demonstrated that, BDG alone or combined treatment partially recovered the low serum IgM levels in splenectomized rats (p<0.001 ve p<0.02, respectively) and completely inhibited oxidative DNA damage in lung and liver after S.pneumoniae infection (p<0.00001). In addition, BDG alone or combined treatment fairly minimized the presence of bacteria in all tissues, when compared with sepsis group (p<0.00001). The data of our study suggests that, BDG, an immunomodulatory agent, alone and in combination with ceftriaxone can reverse the systemic inflammatory reaction in S.pneumoniae sepsis and thereby can reduce multiple organ failure.
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http://dx.doi.org/10.5578/mb.9363DOI Listing
July 2015

The effects of prenatal long-duration exposure to 900-MHz electromagnetic field on the 21-day-old newborn male rat liver.

Turk J Med Sci 2015 ;45(2):291-7

Background/aim: To determine what effect a 900-MHz electromagnetic field (EMF) applied in the prenatal period would have on the liver in the postnatal period.

Materials And Methods: At the start of the study, adult pregnant rats were divided into two groups, control and experimental. The experimental group was exposed to a 900-MHz EMF for 1 h daily during days 13-21 of pregnancy. After birth, no procedure was performed on either mothers or pups. Male rat pups (n = 6) from the control group mothers (CGMR) and male rat pups (n = 6) from the experimental group mothers (EGMR) were sacrificed on postnatal day 21.

Results: Biochemical analyses showed that malondialdehyde and superoxide dismutase values increased and glutathione levels decreased in the EGMR pups. Marked hydropic degeneration in the parenchyma, particularly in pericentral regions, was observed in light microscopic examination of EGMR sections stained with hematoxylin and eosin. Examinations under transmission electron microscope revealed vacuolization in the mitochondria, expansion in the endoplasmic reticulum, and necrotic hepatocytes.

Conclusion: The study results show that a 900-MHz EMF applied in the prenatal period caused oxidative stress and pathological alterations in the liver in the postnatal period.
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http://dx.doi.org/10.3906/sag-1404-168DOI Listing
July 2015

The comparison of the viability of crushed, morselized and diced cartilage grafts: a confocal microscopic study.

Eur Arch Otorhinolaryngol 2015 May;272(5):1135-42

To compare the cellular viability of diced, crushed, and morselized cartilage used in nasal surgeries. In this study, cartilage was extracted from the ears of seven New Zealand rabbits and was subsequently either diced, crushed or morselized to an amorphous state, or left unmodified. The four types of grafts were then implanted in the back regions of the rabbits. After 3 months, the cellular viability from four groups was compared to a control group using confocal microscopy. Analysis of the data obtained from the enumeration of live cells showed no statistically significant difference between the unmodified graft group and the control group. The diced, crushed, and morselized cartilage groups did show a statistically significant difference in terms of live cell count with the highest number of live cells in diced cartilage group. A statistically significant decrease in live cell count was detected in crushed cartilage group. Our study shows that the viability of cells in diced cartilage grafts is greater than those in crushed or morselized cartilage grafts.
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http://dx.doi.org/10.1007/s00405-014-3192-2DOI Listing
May 2015

The protective effects of metyrosine, lacidipine, clonidine, and moxonidine on kidney damage induced by unilateral ureteral obstruction in rats.

Surg Today 2012 Nov 28;42(11):1051-60. Epub 2011 Dec 28.

Department of Pediatric Surgery, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey.

Purpose: To investigate the effects of metyrosine, lacidipine, clonidine, and moxonidine on the renal damage in rats with unilateral ureteral ligation by examining the histological evidence of parenchymal damage and tubular dilatation, as well as biochemical changes indicating cell membrane damage and DNA oxidation.

Methods: Thirty-six albino Wistar rats were randomly divided into six equal groups: a healthy (intact) group, a unilateral ureteral ligation (control) group, and four drug treatment groups given metyrosine (50 mg/kg), lacidipine (2 mg/kg), clonidine (0.075 mg/kg), or moxonidine (0.2 mg/kg), respectively, for 10 days. The latter five groups underwent ligation of the left ureter. Ten days after the operation, we removed both kidneys from each rat in the control and drug treatment groups for renal pathological and biochemical [malondialdehyde (MDA), total glutathione, 8-hydroxy-2-deoxyguanine (8-OH-Gua)] examinations. Spectrophotometric assays were used to detect the malondialdehyde and total glutathione levels of the renal tissue. High-performance liquid chromatography was used to measure the 8-hydroxy-2-deoxyguanine levels.

Results: When the drug treatment groups were compared with the control group, the drug treatment groups' total glutathione level was higher and their malondialdehyde level was lower than that of the control group (P < 0.05), especially in the clonidine group (P < 0.0001). The 8-hydroxy-2-deoxyguanine levels of the drug treatment groups, except the lacidipine group, were significantly lower than that of the control group (P < 0.0001). There was no significant difference between the contralateral kidneys of the treatment groups and control group, according to the biochemical results. As revealed via light microscopy, clonidine and moxonidine treatment significantly reduced the tubular and glomerular damage, as well as the tubular dilation. The interstitial inflammation of the kidneys in the lacidipine group was higher than that of the other treatment groups. However, the apoptotic cell count was at a high level in both the lacidipine and metyrosine groups. The increase in the collagen content was most pronounced in the lacidipine and metyrosine groups. An examination of the contralateral kidneys showed no marked pathological findings.

Conclusions: The use of a direct or indirect α2-adrenergic receptor agonist for the temporary treatment of unilateral ureteral obstruction-induced renal damage may be important for preventing renal structural injury. A more advanced study is necessary to determine the mechanisms underlying the protective effects of these drugs with regard to renal damage in ureteral obstruction.
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http://dx.doi.org/10.1007/s00595-011-0074-8DOI Listing
November 2012

The effects of testosterone on intestinal ischemia/reperfusion in rats.

J Invest Surg 2011 ;24(6):283-91

Department of Surgery, Education and Research Hospital, Yildizkent, Erzurum, Turkey.

ABSTRACT Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.
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http://dx.doi.org/10.3109/08941939.2011.591894DOI Listing
March 2012

Stereological evaluation of the kidneys of anencephalic and normal fetuses.

Ren Fail 2013 20;35(1):110-7. Epub 2011 Jul 20.

Department of Anatomy, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.

The aim of this study is to test the glomerular and other quantitative parameters of kidneys of anencephalic fetuses and comparing those to "normal" fetuses. In this study, 20 kidneys of human fetuses (5 boys and 5 girls of anencephalic fetus, and 5 boys and 5 girls of normal fetus), at gestational ages of 25-30 weeks, were examined. This study is based on two basic research methods: one is a conventional anatomical measurement at the macroscopical level; the other is a design-biased stereological method at the microscopical level. Physical dissector and Cavalieri principle were used to estimate the total and numerical density of glomerulus and the volume of kidney, respectively. The results of the two types of investigation were compared based on anencephalic/normal and boy/girl kidneys at both the macroscopical and microscopical levels. There was no significant difference found between the quantitative features of kidneys (volume of kidneys and mean number and/or height of glomerulus) belonging to anencephalic and normal fetuses. The results of this study suggest that anencephalic fetuses did not differ from normal fetuses in respect of kidneys.
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http://dx.doi.org/10.3109/0886022X.2011.577544DOI Listing
July 2013

The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity.

Toxicol Ind Health 2011 Sep 4;27(8):700-10. Epub 2011 May 4.

Department of Biology, Ataturk University Faculty of Science, Erzurum, Turkey.

This study was designed to investigate the qualitative and quantitative changes in brain tissue following aluminum chloride (AlCl(3)) administration and to determine whether boric acid (BA) has a protective effect against brain damage induced by AlCl( 3). For this aim, Sprague-Dawley rats were randomly separated into eight groups: (1) control, (2) AlCl(3) (5 mg/kg/day), (3, 4 and 5) BA (3.25, 36 and 58.5 mg/kg/day), (6, 7 and 8) AlCl(3) (5 mg/kg/day) plus BA (3.25, 36 and 58.5 mg/kg/day). After the animals were killed, the total numbers of neuron in the brain of all groups were determined using an unbiased stereological analysis. In addition to the stereological analysis, all brains were examined histopathologically by using light and electron microscopy. The stereological and histopathological results indicated a high damage of the rat brain tissues in the AlCl(3) and AlCl(3) + high dose BA (36 and 58.5) treatment groups. However, protective effects on neuron were observed in the AlCl(3) + low dose BA (3.25) group when compared other AlCl(3) groups. Our stereological and histopathological findings show that low-dose BA, as a proteasome inhibitor, can decrease the adverse effects of AlCl(3) on the cerebral cortex.
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http://dx.doi.org/10.1177/0748233710395349DOI Listing
September 2011

Growth hormone reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.

Eur J Obstet Gynecol Reprod Biol 2011 Jul 25;157(1):94-100. Epub 2011 Mar 25.

Department of Pediatric Surgery, Ataturk University School of Medicine, Erzurum, Turkey.

Objective: To evaluate the effects of growth hormone (GH) as an antioxidant and tissue-protective agent and analyse the biochemical and histopathological changes in rat ovaries due to experimental ischemia and ischemia/reperfusion injury.

Study Design: Forty-eight adult female rats were randomly divided into eight groups. In Group 1, a period of bilateral ovarian ischemia was applied. In Groups 2 and 3, 1 and 2 mg/kg of GH was administered, and 30 min later, bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). Group 4 received a 3-h period of ischemia followed by 3h of reperfusion. Groups 5 and 6 received 1 and 2 mg/kg of GH, respectively, 2.5 h after the induction of ischemia. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3h of reperfusion continued. Group 7 received a sham operation plus 2mg/kg of GH. Group 8 received a sham operation only. After the experiments, superoxide dismutase and myeloperoxidase activity and levels of glutathione and lipid peroxidation were determined, and histopathological changes were examined in all rat ovarian tissue.

Results: Ischemia and ischemia/reperfusion decreased superoxide dismutase activity and glutathione levels in ovarian tissue, but increased lipid peroxidation levels and myeloperoxidase activity significantly in comparison to the sham group. The 1 and 2 mg/kg doses of GH before ischemia and ischemia/reperfusion decreased lipid peroxidation levels and myeloperoxidase activity in the experimental groups. The administration of GH before ischemia and ischemia/reperfusion treatments also increased superoxide dismutase and glutathione levels. The histopathological findings also suggested a protective role of GH in ischemia/reperfusion injury. That is, ovarian tissues in the ischemia groups showed histopathological changes, such as haemorrhage, cell degeneration, and necrotic and apoptotic cells, but these changes in the GH groups were lesser. Moreover, in the ischemia/reperfusion groups, acute inflammatory processes--such as neutrophil adhesion and migration, apoptotic and degenerative cells, stromal oedema and haemorrhage--were present. However, the ovarian tissues of the IR+GH (1 mg) group had minimal apoptotic cells, and the IR+GH (2 mg) group had no apoptotic cells. In addition, the general ovarian histological structures of these groups were similar to those of the healthy control group.

Conclusions: The administration of GH is protective against ischemia and/or ischemia/reperfusion-induced ovarian damage. This protective effect can be attributed to the antioxidant properties of GH.
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http://dx.doi.org/10.1016/j.ejogrb.2011.02.012DOI Listing
July 2011

Immunohistochemical and Stereologic Analysis of NF-κB Activation in Chronic Periodontitis.

Eur J Dent 2010 Oct;4(4):454-61

Department of Periodontology, Atatürk University Faculty of Dentistry, Erzurum, Turkey.

Objectives: Nuclear factor kappa B (NF-κB) is a member of the transcription factor family, and it plays a key role in coordinating the expression of genes in many chronic inflammatory diseases. This study investigated the cytoplasmic and nuclear activation of (NF-κB) and the cytoplasmic expression of inhibitor kappa B (IκB) in gingival tissues of subjects who had chronic periodontitis.

Methods: Thirty-five patients were included in this study; 17 patients had chronic periodontitis, and 18 were healthy. Gingival tissues were obtained from each individual and then stained immunohistochemically. The obtained sections were examined under a stereomicroscope, and the numerical density values of the stained cells were computed using the stereologic method. A one-way analysis of variance (ANOVA) and a multiple range least significant difference (LSD) were used for intergroup comparisons (P=0.05).

Results: According to the immunohistochemical analysis of the cytoplasmic positive cells stained with IκB, statistically significant differences were found between the case and control groups. When comparing the cytoplasmic and nuclear positive immunoreactivity of p50 and p65, statistically significant differences were found between the diseased and control groups. Statistically significant correlations were also found between the clinical periodontal scores and the immunohistochemical results of the diseased subjects.

Conclusions: It was shown that NF-κB was highly activated in subjects who had chronic periodontitis, compared to healthy controls. The findings of this study can be useful in planning new treatment strategies for periodontal diseases. Further investigations are needed to understand more about the signaling mechanisms of inflammatory mediators and their interactions with NF-κB in chronic periodontitis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948733PMC
October 2010

Protective effects of montelukast on ischemia-reperfusion injury in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.

Fertil Steril 2011 Mar 20;95(4):1360-6. Epub 2010 Sep 20.

Department of Pediatric Surgery, School of Medicine, Ataturk University, Erzurum, Turkey.

Objective: To reveal the effects of montelukast as an antioxidant and tissue protective agent and study the biochemical and histopathologic changes in experimental ischemia and ischemia-reperfusion (I/R) injury in rat ovaries.

Design: Experimental study.

Setting: Experimental surgery laboratory in a university department.

Animal(s): Forty-eight rats with experimentally induced ovarian torsion.

Intervention(s): Group 1: sham; Group 2: ovarian ischemia; Group 3: a 30-hour period of ischemia followed by a 3-hour reperfusion. Groups 4 and 5: rats administered 10 and 20 mg/kg doses of montelukast before a half-hour of ischemia, then ovarian ischemia applied; after a 3-hour period of ischemia, the bilateral ovaries removed. Groups 6 and 7: 3-hour period of ovarian ischemia applied, then 2.5 hours after the ischemia induction, rats given montelukast. Group 8: sham operation and 20 mg/kg of montelukast; at the end of a 3-hour period of ischemia, 3-hours of reperfusion continued.

Main Outcome Measure(s): Measurement of ovarian tissue concentrations of superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO) and myeloperoxidase (MPO) activity; and histopathologic examination of all ovarian rat tissue.

Result(s): Montelukast treatment normalized changes of LPO and MPO and stimulated an overproduction of endogenous SOD and GSH. The results of the histologic parameters showed that treatment with montelukast in the I/R group of rats ameliorated the development of ischemia and reperfusion tissue injury.

Conclusion(s): Montelukast at different doses attenuates ovarian I/R-induced ovary tissue injury in rats.
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http://dx.doi.org/10.1016/j.fertnstert.2010.08.017DOI Listing
March 2011

Atorvastatin reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.

Naunyn Schmiedebergs Arch Pharmacol 2010 May 27;381(5):455-66. Epub 2010 Mar 27.

Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240 Erzurum, Turkey.

The aim of this study was to evaluate the effects of atorvastatin as an antioxidant and tissue protective agent and study the biochemical and histopathological changes in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. The experiment used 48 adult female rats, and the experimental groups can be summarized as: group I, a sham operation; group II, a sham operation +10 mg/kg atorvastatin; group III, bilateral ovarian ischemia; and groups IV and V, bilateral ovarian ischemia +5 and 10 mg/kg atorvastatin before 30 min of ischemia, respectively (after a 3-h period of ischemia, the bilateral ovaries were surgically removed); group VI, 3-h period of ischemia followed by 3-h reperfusion; groups VII and VIII received 5 and 10 mg/kg atorvastatin, respectively, 2.5 h after the induction of ischemia, and at the end of a 3-h period of ischemia, bilateral vascular clips were removed and 3-h reperfusion continued. After the experiments, superoxide dismutase (SOD) and myeloperoxidase (MPO) activity and levels of glutathione (GSH) and lipid peroxidation (LPO) were determined, and histopathological changes were examined in all rat ovarian tissue. Ischemia and I/R increased the LPO level and MPO activity while decreasing the SOD activity and GSH level significantly in comparison to the sham group. The 5- and 10-mg/kg doses of atorvastatin before ischemia and I/R reversed the trend in LPO level and MPO activity. The levels of SOD and GSH were decreased by ischemia and I/R. The administration of atorvastatin before ischemia and I/R treatments also reversed the trend in the SOD and GSH levels. In the I/R plus atorvastatin groups, although minimal vascular dilation in the ovary stoma and some degenerative cell clusters were seen, most of the cellular structures showed no pathological changes. Administration of atorvastatin is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.
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http://dx.doi.org/10.1007/s00210-010-0504-yDOI Listing
May 2010

Anencephalic fetuses can be an alternative for kidney transplantation: a stereological and histological investigation.

Histol Histopathol 2010 04;25(4):413-22

Department of Anatomy, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.

In the study, stereological, histological, and anatomical techniques were used to investigate structural and morphometrical features of anencephalic and normal fetal kidneys. Twenty human fetal kidneys (5 male and 5 female anencephalic fetuses, and 5 male and 5 female normal fetuses) at gestational ages 30 to 35 weeks were examined. Our study used two basic research methods. One was conventional anatomical measurement at the macroscopic level, such as volume, length, weight, etc. The other consisted of conventional and modern microscopic techniques. The microscopic techniques were based on two research methods: histopathological examination at light microscopic level and stereological estimations, including mean kidney volumes, obtained by the Cavalieri method, and the total number and mean height of the glomeruli via the physical dissector method. There was no statistical difference between the two groups in terms of width, height, weight, and fluid replacement volumes. Microscopic quantitative assessment found no statistical differences either, in terms of the kidney volumes and the number and height of the glomeruli. Our findings suggest that kidneys from anencephalic infants may be a suitable alternative for renal transplantation.
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http://dx.doi.org/10.14670/HH-25.413DOI Listing
April 2010

Evaluation of patients with multiple sclerosis using a combination of morphometrical features and clinical scores.

J Clin Neurosci 2010 Feb 24;17(2):191-5. Epub 2009 Dec 24.

Department of Neurology, Medical School, Ataturk University, Yakutiye, Erzurum 25240, Turkey.

Our aim was to measure cerebellum volume (CV), sclerotic plaque numbers (PN), and plaque surface area (SA) in the parietal lobe, and to investigate the relationship between CV and PN or SA in the parietal lobe, and the clinical status of patients with multiple sclerosis (MS). MRIs were performed in 14 patients with relapsing-remitting MS (RRMS), 13 patients with secondary progressive MS (SPMS), and 26 healthy control participants. The Cavalieri method was used to measure CV and SA. The cerebellum volume was significantly reduced in MS patients compared to controls (p < 0.01). In all patients, CV was negatively correlated with the duration of the disease, relapse number, and Expanded Disability Status Scale (EDSS) scores (p < 0.01). CV was related to mean PN in both the right and left parietal lobes (p < 0.01) and mean SA (p < 0.05) in RRMS patients; CV was also correlated with mean PN (p < 0.01) and mean SA (p < 0.05) in SPMS patients. The progression index (Pi) values were 2.03 +/- 0.4 in RRMS patients and 0.83 +/- 0.2 in SPMS patients (p = 0.023, t = 2.612) (where Pi = EDSS/time from onset in years). We propose that atrophy begins both in the supratentorial and infratentorial areas simultaneously in the RR stage, and that the Cavalieri method can be used to predict SPMS among patients with RRMS.
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http://dx.doi.org/10.1016/j.jocn.2009.04.023DOI Listing
February 2010

The protective effect of beta-1,3-D-glucan on taxol-induced hepatotoxicity: a histopathological and stereological study.

Drug Chem Toxicol 2010 ;33(1):8-16

Department of Biology, Ondokuz Mayis University Faculty of Arts and Science, Samsun, Turkey.

The present study was undertaken to determine the histopathological and quantitative effects of the antineoplastic agent, taxol, on the liver. The protective effects of the strong antioxidant, beta-1,3-D-glucan, against liver damage induced by taxol were also investigated. Mice were divided into four main treatment groups: control, taxol, beta-1,3-D-glucan, and taxol+beta-1,3-D-glucan. Each group was further subdivided into six subgroups, according to time of sacrifice (6, 12, 24, and 48 hours and 7 and 14 days). After the experiments, quantitative and histopathological changes in liver were examined by light microscopy and modern stereological systems. Stereological results indicated that the portal triad area of the taxol group was significantly reduced, compared to the controls at 12 hours, whereas in the taxol plus beta-glucan and beta-glucan groups, the means were similar to those of the controls. There was no statistically significant difference in the numerical density of hepatocytes with time between the control and other groups. The histopathological results indicated an increased, time-dependent degeneration and necrosis of the liver tissues in mice in the taxol group. Regenerative changes in livers of mice in the taxol plus beta-glucan group were observed, when compared with those of the taxol group. Stereological and histopathological results suggest that beta-glucan may reduce taxol-induced hepatic damage by blocking the change in the portal area and suppressing processes leading to necrosis.
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http://dx.doi.org/10.3109/01480540903380472DOI Listing
April 2010

Does haloperidol have side effects on histological and stereological structure of the rat kidneys?

Ren Fail 2009 ;31(7):573-81

Ataturk University, School of Medicine, Departments of Internal Medicine Division of Nephrology, Erzurum, Turkey.

Haloperidol, a typical antipsychotic, is the most commonly prescribed medication for the treatment of mental health problems such as agitation and psychosis. We attempted to determine the effects of haloperidol treatment on the kidneys of female rats. In addition, we aimed to estimate the numerical density, total number, and height of renal glomeruli and the volume and volumetric fractions of the cortex, medulla, and whole kidneys, and tried to determine whether there was a change in these stereological parameters depending on haloperidol treatment. Both the qualitative and quantitative histological features of the kidney samples were analyzed with conventional histopathological and modern stereological methods at the light microscopic level. The total number of glomeruli and numerical density of glomerulus in the haloperidol-treated groups was not changed by increasing the dose in comparison to the control group. The mean height of the glomerulus significantly increased, especially in low-dose groups. In the haloperidol-treated groups, the volumetric fractions of the cortex to the whole kidney of the rats were significantly decreased by increasing the dose. The volumetric fractions of the medulla to the whole kidney of the rats were increased significantly in parallel by the given dose. In addition, we present quantitative findings showing that haloperidol is associated with many alterations in rat kidneys. It was shown that haloperidol may lead to undesirable changes in the kidney after chronic treatment with especially high doses.
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http://dx.doi.org/10.1080/08860220903060776DOI Listing
January 2010

Long-term treatments with low- and high dose olanzapine change hepatocyte numbers in rats. A stereological and histopathological study.

Arch Med Res 2009 Apr 8;40(3):139-45. Epub 2009 Apr 8.

Department of Histology and Embryology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.

Background And Aims: Olanzapine, an atypical antipsychotic agent, has been commonly used to treat schizophrenia and bipolar mania because it demonstrates better efficacy for negative schizophrenic symptoms and has minimal extrapyramidal side effects compared to typical antipsychotic drugs. Recent reports of serious hepatotoxicity induced by olanzapine have been published. In this study we aimed to evaluate the effects of long-term administration of low and high doses of olanzapine on rat livers.

Methods: Rats were divided into a control group (n = 5) (CG), a low-dose olanzapine group (n = 5) (LOG) and a high-dose olanzapine group (n = 5) (HOG). Olanzapine in doses of 2 and 4 mg/kg daily for 6 weeks were intraperitoneally injected into the LOG and HOG, respectively. The same volume and dosages of normal saline (0.9% NaCl) were given to the CG during the same period. At the end of the experiment, livers were evaluated stereologically and histopathologically.

Results: Significant differences only in the total number of hepatocytes in the rats' livers were found between CG, and LOG and HOG (p <0.05). The livers' general architecture appeared normal in CG, LOG and HOG.

Conclusions: Findings of the present study indicate that either low or high doses of olanzapine damaged the rat livers at a cellular level.
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http://dx.doi.org/10.1016/j.arcmed.2009.02.006DOI Listing
April 2009

Does telmisartan prevent hepatic fibrosis in rats with alloxan-induced diabetes?

Eur J Pharmacol 2009 Jul 3;614(1-3):146-52. Epub 2009 May 3.

Department of Pharmacology, Ataturk University School of Medicine, Erzurum, Turkey.

Background/aims: This study evaluated the effect of telmisartan on the livers of diabetic rats and also aimed to determine the hepatic distribution and role of transforming growth factor beta (TGF-beta) in diabetes-related hepatic degeneration while taking into account the possible protective effects of telmisartan.

Methods: Fifteen adult male rats were used and divided into three groups: the non-diabetic healthy group, alloxan-induced diabetic control group, and the alloxan-induced diabetic telmisartan group. The non-diabetic healthy group and the diabetic control group were exposed to saline for 30 days, while the group treated with diabetic drugs was orally administered telmisartan for 30 days (10 mg/kg/day). At the end of the experiment, the rats were sacrificed and the livers were dissected and transferred into the fixation solution. The livers were then evaluated using stereological and histopathological methods.

Results: Our study of the numerical density of hepatocytes shows a significant difference between the diabetic control group and diabetic rats treated with telmisartan. Immunohistochemical staining for TGF-beta in liver sections of the diabetic rats treated with telmisartan showed no immunoreactivity. The diabetic control group was determined to be strongly immunoreactive to TGF-beta.

Conclusion: Results suggest that telmisartan may reduce type-I diabetes mellitus-induced hepatic injury by suppressing activated hepatic stellate cells through concomitant TGF-beta1 down-regulation.
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http://dx.doi.org/10.1016/j.ejphar.2009.04.042DOI Listing
July 2009

Protective effects of telmisartan on ischemia/reperfusion injury of rat ovary: biochemical and histopathologic evaluation.

Fertil Steril 2010 Mar 6;93(4):1299-307. Epub 2009 Feb 6.

Department of Obstetrics and Gynecology, Ataturk University School of Medicine, Terminal cad no. 14/2, 25200 Erzurum, Turkey.

Objective: To evaluate the effects of telmisartan as an antioxidant and for its tissue protective properties and to study the biochemical and histopathologic changes in experimental ischemia and ischemia/reperfusion injuries in rat ovaries.

Design: Experimental study.

Setting: Experimental surgery laboratory in a university department.

Animal(s): Forty-eight female adult rats.

Intervention(s): I: sham operation; II: bilateral ovarian ischemia; III: 3 h ischemia + 3 h reperfusion. IV and V: Rats were administered 10 and 20 mg/kg doses of telmisartan, respectively, before 0.5 h of ischemia, and then ovarian ischemia was applied; after 3 h of ischemia, the ovaries were removed. VI and VII: 3 h ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of telmisartan; at the end of 3 h of ischemia, the ovaries were removed and a 3 h reperfusion followed.

Main Outcome Measure(s): Superoxide dismutase, inducible nitric oxide synthase, and myeloperoxidase activity in rat ovarian tissue; and histopathologic changes in the ovarian tissue of the rats.

Result(s): Ischemia and ischemia-reperfusion increased the inducible nitric oxide synthase and myeloperoxidase activity while decreasing the super oxide dismutase activity significantly in comparison with the sham group. Before ischemia and ischemia/reperfusion, telmisartan reversed the trend in inducible nitric oxide synthase activities and the level of myeloperoxidase.

Conclusion(s): telmisartan is effective in reversing tissue damage induced by ischemia/reperfusion in ovaries.
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http://dx.doi.org/10.1016/j.fertnstert.2008.12.016DOI Listing
March 2010

Effects of trimetazidine on crush injury of the sciatic nerve in rats: a biochemical and stereological study.

Brain Res 2009 Jan 21;1247:11-20. Epub 2008 Oct 21.

Department of Neurosurgery, Tayfur Ata Sokmen Medical Faculty, Mustafa Kemal University, 31100 Hatay, Turkey.

Trimetazidine (TMZ) is an anti-ischemic agent which has been used for years as an effective anti-anginal agent in cardiac patients. The aim of the study was to investigate the effect of TMZ on the level of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), catalase (CAT), histopathological changes and the number of myelinated axons in a crush injury model of sciatic nerve in rats. In this study, 50 Wistar albino rats were used and the right sciatic nerves of all animals were injured. They were randomly divided into two groups equal in number, called treatment and non-treatment groups. The animals were subdivided into four subgroups, non-injury/non-treatment (left sciatic nerves of non-treatment animals, NI-NT) and non-injury/treatment (left sciatic nerves of treatment animals, NI-T) and injury/non-treatment (right sciatic nerves of non-treatment animals, I-NT) and injury/treatment (right sciatic nerves of treatment animals, I-T). At the end of the experiment, the bilateral sciatic nerves and blood samples collected from these animals were analyzed using histological, stereological and biochemical methods. There was a progressive increase in the serum level of GSH and progressive decrease in serum MDA levels in the treatment group. Progressive decrease in serum NO levels was observed in the treatment groups and it was statistically significant on day 14 (p<0.05) compared to the non-treatment group. The activities of CAT were low in the treatment groups on days 21 (p<0.05) and 42 (p<0.05). In the NI-NT group, some unimportant degenerative changes such as irregularity in myelin sheets were observed. Many pathologic changes in the I-NT group and some minimal degeneration in the I-T group were observed. TMZ treatment resulted in increases in the myelinated axon numbers by a range of 223 to 604 in the I-NT group compared to the I-T. In conclusion, TMZ appears to be beneficial for induction of axonal regeneration and myelination in healthy nerves as well as injured nerves.
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http://dx.doi.org/10.1016/j.brainres.2008.10.007DOI Listing
January 2009

Effect of chronic treatment of haloperidol on the rat liver: a stereological and histopathological study.

Naunyn Schmiedebergs Arch Pharmacol 2009 Mar 21;379(3):253-61. Epub 2008 Oct 21.

Department of Pharmacology, Ataturk University School of Medicine, 25240, Erzurum, Turkey.

Haloperidol is commonly used in therapy for patients with acute and chronic schizophrenia. Because it can have some adverse effects on specific target organs such as the liver, we analyzed whether haloperidol exerts a toxic effect on rat liver by means of stereological and histopathological methods. Fifteen adult male rats, divided into three groups, were used in the experiments. Once a day for 6 weeks, either saline or 0.4 or 0.8 mg kg(-1) doses of haloperidol were given interperitoneally to the control, low-dose, and high-dose groups, respectively. At the end of the experiment, rats were killed by an overdose of a general anesthetic, and the livers were dissected out, fixed for sectioning, and evaluated using stereological and histopathological methods. Hepatocyte numbers were found to be 271.672, 291.072, and 238.415 hepatocytes per cubic millimeter in the liver of the control, low-dose, and high-dose groups, respectively. The differences between high-dose and control groups and also between high-dose and low-dose groups were significant (p < 0.05). Our histopathological findings at both the structural and the ultra-structural level were confirmed by stereological estimations. Results suggest a relationship between haloperidol dose and toxic effects on the liver, and they indicate that a high dose of haloperidol may result in irreversible liver damage.
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http://dx.doi.org/10.1007/s00210-008-0362-zDOI Listing
March 2009

Chronically administered risperidone did not change the number of hepatocytes in rats: a stereological and histopathological study.

Basic Clin Pharmacol Toxicol 2008 May 30;102(5):426-32. Epub 2008 Jan 30.

Department of Pharmacology, Ataturk University School of Medicine, Erzurum, Turkey.

Risperidone, an antipsychotic agent, has been used in the therapy of patients with acute and chronic schizophrenia. The strategy in the choice of antipsychotic agent should take into account the hepatic tolerance. The aim of the present study was to analyse whether or not the chronic administration of risperidone has a toxic effect on rat livers. Rats were divided into three groups. Low dose (n = 5) and high dose (n = 5) groups that were given 0.5 and 1 mg/kg intraperitoneal doses of risperidone daily for 6 weeks, respectively. The control group received distilled water as a vehicle. At the end of the experiment, the rats were killed, and livers were dissected out immediately and transferred into the fixation solution. Both conventional light and transmission electron microscopic tissue preparation procedures were applied to liver tissues and they were evaluated using stereological and histopathological methods; in this respect, this is the first study using stereological methods for searching the effects of risperidone on liver. There were no significant differences about the total hepatocyte number and their numerical density of rat liver between groups (P > 0.05). Stereological results were also confirmed by the histopathological findings that come from both structural and ultrastructural levels examination. The results of the current study indicate that neither low nor high doses of risperidone resulted in damage to the rat livers at cellular level. In conclusion, we did not find any evidence for hepatotoxicity of risperidone rats. Larger-scale, prospective studies are needed in order to confirm these findings.
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http://dx.doi.org/10.1111/j.1742-7843.2007.00198.xDOI Listing
May 2008

Protective effects of amlodipine on ischemia-reperfusion injury of rat ovary: biochemical and histopathologic evaluation.

Fertil Steril 2008 Dec 21;90(6):2408-15. Epub 2008 Feb 21.

Department of Pharmacology, Ataturk University School of Medicine, Erzurum, Turkey.

Objective: To evaluate the effects of amlodipine as an antioxidant and analyze the histopathologic changes in experimental ischemic and ischemic-reperfusion (I/R) injury in rat ovaries.

Design: Experimental study.

Setting: Experimental surgery laboratory.

Animal(s): Forty-two rats with experimentally induced ovarian torsion.

Intervention(s): Group 1: sham operation; group 2: bilateral ovarian ischemia; group 3: 3-hour period of ischemia plus 3 hours of reperfusion; groups 4 and 5: amlodipine administration at 3 and 5 mg/kg respectively before one half hour of ischemia, and then bilateral ovarian ischemia. The ovaries were removed at the third hour of ischemia. Groups 6 and 7: 3-hour period of bilateral ovarian ischemia. Two and a half hours after the induction of ischemia, the rats received amlodipine. At the end of a 3-hour period of ischemia, 3 hours of reperfusion was continued; then the ovaries were removed.

Main Outcome Measure(s): Ovarian tissue superoxide dismutase and nitric oxide activity; histopathologic examination of all ovarian rat tissue.

Result(s): Ischemia and I/R increased the inducible nitric oxide synthase activity while decreasing the superoxide dismutase activity significantly in comparison with the sham group. Both doses of amlodipine before ischemia and I/R reversed the trend in nitric oxide synthase activities and reversed the trend in the rat's ovary.

Conclusion(s): Conservative treatment with amlodipine is effective in reducing tissue damage induced by ischemia, I/R, or both in ovaries.
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http://dx.doi.org/10.1016/j.fertnstert.2007.10.007DOI Listing
December 2008
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