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.

From Nose to Lumbar Spinal Cord - Reduced Sperm Numbers Occur by Olfactory Bulbectomy-Related Onuf's Nucleus Degeneration: New Experimental Evidence for Kallmann Syndrome.

INTRODUCTION: Olfaction and its relation to human health is an area of growing interest. Although olfaction disorders have been considered a part of Kallmann syndrome, the role of olfactory dysfunction on spermatogenesis has not been studied yet. We studied if olfactory bulbectomy (OBX) causes dysfunction in spermatogenesis as a result of Onuf's nucleus damage. METHODS: Twenty-eight male rats were divided into three groups: six as the control (G-1; n = 6), six as the only frontal burr hole applied animals SHAM (G-2; n = 6), and 16 as the study group (G-3; n = 16) in which OBX was performed. The animals were followed for 2 months. After the decapitation of the animals, olfactory bulb (OB) volumes (mm3), the neuron density of the Onuf's nucleus (n/mm3), and sperm density (n/mm3) were estimated stereologically and analyzed. RESULTS: OB volumes (mm3), degenerated neuron density of Onuf's nucleus (n/mm3), and sperm numbers of control, SHAM, and study groups were estimated as: 4 ± 0.5; 6 ± 2 and 103.245 ± 10.841 in G-1; 3.5 ± 0.7; 14 ± 4 and 96.891 ± 9.569 in G-2; and 1.3 ± 0.3; 91 ± 17 and 73.561 ± 6.324 in G-3. The statistical results of degenerated neuron density of Onuf's nucleus and sperm numbers between groups are p < 0.005 for G-1/G-2; p < 0.0005 for G-2/G-3; and p < 0.00001 for G-1/G-3. DISCUSSION: This study first time indicates that Onuf's nucleus degeneration secondary to OBX seems to be responsible for reduced sperm numbers.

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.

A novel method for flap delay vacuum assisted flap delay: an experimental study in rabbits.

Flaps are the workhorse of plastic surgery practice. The delay procedures have been defined to prevent flap necrosis. The golden standard method of delay is a surgical delay. On the other hand, a major drawback of surgical delay is two sessions of surgery. Efforts have been made to omit one session and increase the patient safety and decrease the costs. The writer's aim was to evaluate the effects of topical negative pressure, applied prior to flap elevation, on flap survival, perfusion and compare the results with the surgical delay. In a rabbit random flap model, prior to elevation, the writers used a topical negative pressure system on the lateral thoracic region of, for induction of delay and compared the results with surgical delay and the control group. The total and necrotic flap areas, necrosis ratio, histomorphometric vascular density, immunohistochemical evaluation of neovascularization (CD31/CD34), Laser Doppler images and computerized tomography contrast uptake were used to compare the groups. In all of the parameters, the vacuum assisted flap delay was equivalent to surgical delay. Both were superior to non-delayed flaps. Control group had 65.56 ± 18.02% flap necrosis rate, while Surgical Delay group had 37.31 ± 30.74% and Vacuum Assisted Flap Delay group had 19.58 ± 27.35%. Vacuum Assisted Flap Delay did not require an extra operation for the delay procedure. The mechanism of action in the vacuum-assisted flap delay is unclear. The clinical significance should be studied further. However, vacuum assisted flap delay seems to be a promising method in the clinical setting.

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.

Comparing effects of lacidipine, ramipril, and valsartan against experimentally induced myocardial infarcted rats.

In this study, the effects of lacidipine (LAC), ramipril (RAM), and valsartan (VAL) on biochemical and histopathologic changes in heart tissue were studied in rats with isoproterenol-induced (ISO-induced) myocardial infarction (MI). LAC, RAM, and VAL had been administered via oral gavage at 3, 3, and 30 mg/kg doses, respectively, once per day during a 30-day time period. On days 29 and 30, the drug treatment group and the control group (with the exception of the intact control group, in which no medications were given, and ISO was not administered) were administered 180 mg/kg ISO subcutaneously over an interval of 24 h. After this period, the hearts of the rats were removed and processed for biochemical and histopathologic studies. The antioxidant parameters superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were estimated. A diagnosis of MI was confirmed with antioxidant parameters and histopathologic findings. In MI control groups, histopathologic indicators were found to be statistically higher than those in drug groups; an increase in histopathologic indicators of MI correlates with significant decreases in SOD and CAT levels, and an increase in MDA level. Histopathologic grades of MI indicators were significantly higher in MI group that did not receive any cardioprotective medications in comparison with MI groups that received LAC, RAM, and VAL. Each of the three medications favorably modulated most of the biochemical and histopathologic parameters observed. No significant difference existed with regard to any of the estimated parameters in the rat groups that received medications without MI induction. In conclusion, results indicate that LAC, RAM, and VAL significantly reduced myocardial injury and emphasize the cardioprotective nature of these agents.

A new hypothesis about neuronal degeneration appeared after a rat model of menopause.

OBJECTIVE: Estrogen is suggested to be one of the most important regulators of neuronal function, including neuronal proliferation, survival and plasticity. There is a broad consensus that the loss of ovarian hormones is associated with neurodegeneration in the hippocampus that leads to cognitive impairment. METHODS: A total of 8 female rats which were subjected to bilateral ovariectomy were included in this study. After ovariectomy, the rats were housed for 123 days in a standard laboratory. At the end of the 123 days, the rats were euthanized and the brain sections were investigated by conventional light microscopic and electron microscopic techniques. RESULTS: The regular structure of almost all axon extensions was lost. The majority of these extensions had a sawtooth-like appearance in longitudinal section profiles. Especially in transfer section profiles of myelinated axons, some morphological changes were shown which may be matched up with light microscopic findings. CONCLUSIONS: Deficiency of estrogen will initially affect microtubule organization. When this organization breaks down, it will physically cause the distribution of the normal structure of axonal plasmalemma. This in turn will lead to the distribution of physical organizations of estrogen and other different types of receptors which are placed in both the membrane and microtubules in the axon.

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.