Nicotinamide Mononucleotide and Nicotinamide Riboside Reverse Ovarian Aging in Rats Via Rebalancing Mitochondrial Fission and Fusion Mechanisms.

PURPOSE: This study examined the effects of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) on folliculogenesis and mitochondrial dynamics (fission and fusion mechanisms) in ovaries of middle-aged female rats. METHODS: Experimental groups were young, middle-aged (control), middle-aged + NMN and middle-aged + NR. NMN was administered at a concentration of 500 mg/kg intraperitoneally but NR at a concentration of 200 mg/kg by gavage. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were analyzed by ELISA. Hematoxylin-eosin staining sections were used for histopathological examination and follicles-counting. Expression levels of mitochondrial fission (Drp1, Mff and Fis1) and fusion (Mfn1, Mfn2, Opa1, Fam73a and Fam73b) genes as well as Sirt1 gene were analyzed by RT-PCR. Expression levels of fission-related proteins (DRP1, MFF, FIS1 and SIRT1) were analyzed by Western Blot. RESULTS: Higher ovarian index, more corpus luteum and antral follicles were detected in NMN and NR groups compared to the control. NMN or NR could rebalance LH/FSH ratio. The control group was determined to possess higher expression levels of fission genes and lower expression levels of fusion genes when compared the young group. In comparison with the control group, both NMN and NR group were found to exhibit less mitochondrial fission but more mitochondrial fussion. Higher gene and protein levels for Sirt1 were measured in NMN and NR groups compared to the control group. CONCLUSION: This study reveals that NMN alone or NR alone can rebalance mitochondrial dynamics by decreasing excessive fission in middle-aged rat ovaries, thus alleviating mitochondrial stress and correcting aging-induced folliculogenesis abnormalities.

Overlooked evidence for transmission deficit of pupillary light reflex can be secondary to trigeminal nerve ganglion degeneration following subarachnoid hemorrhage; preliminary experimental study.

OBJECTIVE: Although the effect of oculomotor and cervical sympathetic networks on pupil diameter is well known; the effect of the trigeminal nerve on pupil diameter has not been investigated yet. This subject was investigated. MATERIALS AND METHODS: Five of 23 rabbits were used as a control group (GI; n = 5); 0.5 ccs saline solution into cisterna magna injected animals used as SHAM (GII; n = 5); autologous blood injected to produce SAH used as the study group (GIII; n = 13) and followed up three weeks. Light-stimulated pupil diameters were measured with an ocular tomography device before, middle, and at the end of the experiment. Considering the sclera area/pupil area ratio index (PRI) as the pupillary reaction area, we used this equation for the pupil's rush to light. Degenerated neuron densities of trigeminal ganglia and pupil diameters compared with the Mann-Whitney U test. RESULTS: The PRI, degenerated neuron density of trigeminal ganglia (n/mm3) were: (2.034 ± 0.301)/(13 ± 3) in GI; (1.678 ± 0.211)/(46 ± 9) in GII; and (0.941 ± 0.136)/(112 ± 21) in GIII. P-values between groups as: p < 0.005 in GI/GII; p < 0.0001 in GII/GIII and p < 0.00001 in GI/GIII. CONCLUSION: Light stimulates the cornea which is innervated by the trigeminal nerves. This experimental study indicates that the pupil remains mydriatic as the cornea is damaged by trigeminal ischemia following SAH and blocks the light flow.

Nicotinamide Riboside Preserves Ovarian Injury in Experimental Sepsis Model in Rats.

OBJECTIVE: The aim of the study is to investigate the protective effects of nicotinamide riboside on oxidative stress in an experimental sepsis model created by cecal ligation and puncture. MATERIALS AND METHODS: Rats were divided into 3 groups randomly: sham-operated (control) group, sep- sis group, and nicotinamide riboside-treated group. Sepsis model-induced cecal ligation and puncture was applied to sepsis group rats. Animals in the nicotinamide riboside-treated group were administered nicotin- amide riboside intraperitoneally (500 mg/kg). Tissue specimens from rats were biochemically calculated for their activities of catalase, superoxide dismutase, glutathione peroxidase, myeloperoxidase, and malondialde- hyde levels. Ovarian tissues of all rats were histopathologically evaluated. RESULTS: Catalase, superoxide dismutase, and glutathione peroxidase activities were lower in the sepsis group compared to the sham-operated (control) group. Superoxide dismutase activity was significantly higher in the nicotinamide riboside-treated group than in control and sepsis group (P <.05). Myeloperoxidase activi- ties and mean malondialdehyde concentration of ovarian tissue were lower in nicotinamide riboside-treated group than in sepsis group (P<.05). The light microscopic assessment revealed that ovarian tissue was protected, and inflammation and interstitial edema decreased in nicotinamide riboside-treated group. The follicular damage findings were notably decreased in nicotinamide riboside-treated group in comparison to sepsis group (P<0.05). CONCLUSION: Our findings indicated that nicotinamide riboside diminished ovarian injury in sepsis via inhibiting tissue infiltration and increasing endogenous antioxidant capacity. Nicotinamide riboside administration may represent a new treatment approach for the prevention of sepsis-induced ovarian injury.

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

This study was performed to investigate whether the toxicity of nanoparticles (Ag NPs or TiO2 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), TiO2 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 TiO2 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 TiO2 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 TiO2 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.

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

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.

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

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.

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

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.

[Investigation of the protective effects of beta-D-glucan against invasive encapsulated Streptococcus pneumoniae sepsis in splenectomized rats]. / Splenektomili siçanlarda kapsüllü invazif Streptococcus pneumoniae sepsisinde beta-D-glukanin koruyucu etkilerinin arastirilmasi.

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.

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

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.

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

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.

Stereological evaluation of the kidneys of anencephalic and normal fetuses.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.