Protective effects of beta glucan in brain tissues of post-menopausal rats: a histochemical and ultra-structural study.

Decline of estrogen during menopause has been associated with numerous significant changes that have been linked to many pathophysiological complications. In addition, ovarian hormone deficiency increases the production of reactive oxygen radicals which could result in oxidative stress and cell damage. While estrogen therapy is often considered to overcome the behavioral and physiological shortcomings, antioxidants are gaining popularity for their beneficial property. For this purpose, in the present study, utilizing the antioxidant properties of beta glucan has been examined in treatment of menopause induced oxidative stress in cerebral neurons. Four groups of female Wistar rats were used: control, ovariectomy, ovariectomy + estrogen treated and ovariectomy + beta glucan treated. We observed a significant increase in neural degeneration in ovariectomized rats as compared to controls. Moreover, increased oxidative stress in the brains of the ovariectomized rats has been detected by performing immunohistochemical analysis. A large number of immuno-positive cerebral neurons have been observed in ovariectomy group rat brains. Interestingly, providing beta glucan treatment to ovariectomized rats reduced the number of degenerated neurons. Our study is the first to examine light and electron microscopic examination and immunohistochemical and stereological analysis of estrogen depletion in rats and to test protective role of beta glucan in the experimental study.

Effect of mercury vapor inhalation on rat ovary: Stereology and histopathology.

AIM: Mercury, an environmental contaminant, is a risk factor for health in whole living organisms. In this study, we investigated whether mercury vapor (HgO) inhalation has an effect on rat ovary. METHODS: Twelve Wistar albino rats were divided equally into experimental (Hg) and control groups (n = 6). Animals in the Hg group were exposed to HgO for 45 days at a dose 1 mg/m(3)/day, after which, histological and stereological assessment were carried out. RESULTS: Ovaries exposed to HgO had histo-morphometric alterations. HgO inhalation resulted in reduction of the total number of primordial, primary and Graaf follicles. Also, mean volume of ovary, medulla and cortex, corpus luteum (c. luteum) and Graaf follicles was decreased in the Hg group. Moreover, there was a significant increase in total volume of the atretic follicles. On light microscopy, thickening of tunica albuginea, increase of fibrils within the connective tissue, congestion of the capillaries and venous vessels, thinned walls and fibrin deposition in some large blood vessels, and edema were seen. Also, irregular follicle and oocyte borders, and hydropic degeneration in follicular granulosa cells were detected. CONCLUSION: Structural alterations could be attributed to the toxic influence of HgO on rat ovary. The use of Hg should therefore be more controlled to minimize its toxic effect.

Protective effects of estrogen and bortezomib in kidney tissue of post-menopausal rats: an ultrastructural study.

PURPOSE: Symptoms and disorders related to menopause and its associated estrogen deficiency have become a considerable health concern worldwide. Ovarian hormone depletion/estrogen deficiency can be usefully studied using animal models after removal of the ovaries [ovariectomy (Ovx)]. This study assessed renal changes after Ovx-induced estrogen deficiency in a rat model. METHODS: Rats were randomly allotted into one control group (group I, healthy) and three study groups (group II, Ovx group; group III, Ovx +17ß-estradiol group; and group IV, Ovx + bortezomib group). RESULTS: In the Ovx group (group II), thickening of glomerular capillary walls, narrowing of Bowman's capsular space, glomerular hypertrophy, atrophic tubules, and loss of the basal membranes of the tubules were observed. Mesangial cell proliferation was observed, particularly in the glomerulus. Immunohistochemical (IHC) staining studies in this group showed dense staining in the mesangial cells, tubular cell Nf-KB/p65, and caspase-3. Groups III and IV (Ovx +17ß-estradiol and Ovx + bortezomib) showed decreased NF-kB/p65 and caspase-3 expression compared with the Ovx group (p < 0.05). CONCLUSION: In renal failure related to estrogen deficiency caused by Ovx, 17ß-estradiol and bortezomib have a protective effect on renal tissue.

The role of infliximab on paracetamol-induced hepatotoxicity in rats.

Paracetamol has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Infliximab is tumor necrosis factor alpha (TNF-α) inhibitor agent, which has been developed as a therapeutic agent for TNF-α-mediated disease. It acts by binding and neutralizing TNF. The aim of our study was to evaluate the hepatoprotective activity of infliximab on paracetamol-induced hepatotoxicity and to understand the relationship between the TNF-α and paracetamol-induced liver injury. Fifty-six rats were divided into eight groups as each composed of seven rats: (1) intact, (2) 7 mg/kg infliximab, (3) 140 mg/kg NAC, (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 3 mg/kg infliximab, (7) 2 g/kg paracetamol + 5 mg/kg infliximab and (8) 2 g/kg paracetamol + 7 mg/kg infliximab groups. Liver function tests including lipid peroxidation levels were analyzed and histopathological changes of liver were also observed. There were statistically significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), levels of TNF-α and malondialdehyde (MDA) and decreases in the activity of superoxide dismutase (SOD) and level of glutathione (GSH) in the group treated with paracetamol. Infliximab administration dramatically reduced serum ALT, AST and TNF-α level. Also, it restored GSH, SOD and decreased MDA levels in liver. Liver histopathological examination showed that infliximab administration antagonized paracetamol-induced liver pathological damage. The results of present study suggest that infliximab has significant hepatoprotective activity on paracetamol-induced hepatotoxicity.

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.

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.

Chronic treatment of haloperidol induces pathological changes in striatal neurons of guinea pigs: a light and electron microscopical study.

In the present work, we investigated whether there would be any change in histological structure of striatal neurons after haloperidol applications at different doses. Adult male guinea pigs were treated once-daily with saline (group 4, control) or haloperidol during 6 weeks, and the dose was 1, 2, or 3 mg/kg (groups 1, 2, and 3, respectively). After treatment, all animals were anesthetized and striata were dissected and examined. When striata were evaluated histologically, dark neurons and some degenerating striatal neurons had distinctive morphological changes consistent with cell death, including reduced neuronal size with nuclear and cytoplasmic shrinkage. Also, in sections of striata in groups 1 and 2, but not in group 3, more glial cells were observed than in those of the control group. In all treated groups, fibrous content of intersititium was paralelly increased by increasing dose. Ultrastructural investigation of striatal neurons in haloperidol-treated rats showed notched nuclei and many lysosomes. Moreover, degeneration of myelin, scarce microglial macrophages, expansion of nuclear intermembranous space, degenerated mitochondria, and vacuoles were found. Also, cytoplasmic swelling, lysosomes, and apoptotic bodies were present. These results suggest that haloperidol treatment may lead to damage in neurons via the necrotic process in both low- and high-dose applications.

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.

The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats.

OBJECTIVES: Sepsis model was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or concomitantly, on the response of the activity of the nuclear factor kappa B (NF-kappaB) and the oxidative response in kidney. SUBJECTS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Diabetes was induced in female rats using administration of alloxan. The rats were divided into five groups: sham control (group 1), ovariectomy (group 2), ovariectomy + sepsis (group 3), ovariectomy + diabetes (group 4), and ovariectomy + diabetic + sepsis (group 5). RESULTS: In kidney tissues, the levels of lipid peroxidation (LPO) and glutathione (GSH) and the activity of catalase (CAT) were higher for groups 3, 4, 5 than the control groups. Superoxide dismutase (SOD) activity was lower for groups 3, 4, 5 than the control groups. We determined that CLP produced injury evident in the kidneys of rats when compared to the control group, whereas the severity of the injury was higher in the diabetes + ovariectomy + CLP group when compared to the CLP group. In immunohistochemical staining, we determined that CLP operation increased NF-kappaB activation. In the ovariectomized, septic, and diabetic group, NF-kappaB activation was significantly higher than other groups. CONCLUSIONS: Hyperglycemia and ovariectomy severely increased NF-kappaB activation and oxidant levels with the stages of our sepsis model. Ovariectomy resulted in general changes in metabolism, which are seen in the kidney with diabetes under sepsis conditions.

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

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.

The effects of high-fat diet on the renal structure and morphometric parametric of kidneys in rats.

To characterize the kidney in a high-fat-induced obesity model, we examined the renal structure of adult Sprague-Dawley rats fed a control diet or a high-fat diet for 3 months. Ten adult female Sprague-Dawley rats were fed a diet consisting highly of fat (30%) for a period of 3 months. Ten control rats were maintained with standard rat chow. All animals were weighed every 10 days for 3 months. At the end of the experiment, the naso-anal length of the anaesthetized rats was measured to calculate body mass index, and subsequently whole kidneys of intracardially formalin-perfused animals were removed. Quantitative features of the kidney were analysed with the Cavalieri and physical dissector methods applied to serial paraffin sections. Kidney samples were also examined histologically. The body mass indices of the control and treatment groups were 4.528 +/- 0.242 and 5.876 +/- 0.318 kg m(-2), respectively. The difference between the body mass indices of the two groups was statistically significant (P < 0.01, Mann-Whitney U-test), suggesting that the animals fed with a high-fat diet may be overweight. Stereological examination of the kidneys revealed differences in kidney weight, total kidney volume, volume of cortex, medulla, glomeruli, proximal and distal tubules, and numerical density of glomeruli and glomerular height in the treatment group compared with the control group. Light microscopic investigation showed a dilatation in blood vessels and Bowman's space, mononuclear cell infiltration, degeneration in nephrons, including glomerulosclerosis and tubular defects, and an increase in the connective tissue in the kidneys in the treatment group. We concluded that a fatty diet is responsible for the rats' obesity and may lead to renal deformities as a result of histopathological changes such as dilatation, tubular defects, inflammation and connective tissue enlargement of the kidney.

The effect of autogenous vein grafts on nerve repair with size discrepancy in rats: an electrophysiological and stereological analysis.

Aside from anatomical repairs, the reestablishment of sensory and motor innervations for proper functional recovery is one of the fundamental objectives of reconstructive surgery. The heterotopic transfer of autologous tissues is likely to result in a size discrepancy between the donor and recipient nerves, which will have a negative influence on regeneration. Twenty Wistar albino female rats were used in a study that was divided into two main groups: tibial-peroneal (TP) and peroneal-tibial repair (PT). Both types of nerves were exposed on the hind legs with the nerves cut on the right side, while the proximal stump of the tibial nerve and distal stump of the peroneal nerve were sutured to each other. These groups are also called end-to-end neurorrhaphy groups (EtoE). On the left side, the tibial and peroneal nerves were cut on the same level as on the right side. After the end-to-end epineural suturing of the nerve, the vein graft was slid over to the repair zone under irrigation. These are called the vein graft group (VG). All processes mentioned above were also done for the PT group. On the 90th postoperative day, anesthetized animals were fixed prone on a board, with the nerves carefully dissected for electrophysiological recording. Stereological methods for an estimation of the total number of myelinated fiber, a mean axonal cross-section area and the thickness of the myelin sheet were used. In TP and PT groups, nerve conduction velocities were found to be higher within the VG group. Nevertheless; the difference was only significant in the PT group. In both TP and PT groups, the increase in the axon number, axon area and myelin thickness were statistically different in favor of the vein graft sides. An appearance of vacuoles and degenerated pertinacious material within the myelin sheath of EtoE sides was seen. A histomorphological examination of the sections proximal to, from, and distal to the repair zone over three months revealed less epineural scarring, a thinner epineurium, more regenerated axons and fewer inflammatory cells in groups where vein grafting was used, because the vein graft provided additional mechanical and chemical support in the size discrepancy of the nerve regeneration.

Effect of a high fat diet on quantitative features of adipocytes in the omentum: an experimental, stereological and ultrastructural study.

BACKGROUND: Omental adipose tissue specimens of female rats that were fed a high fat (HF) diet were evaluated stereologically and histopathologically. To our knowledge, there is no stereological study on numerical density, nuclear height and volume of adipocytes in omental adipose tissue in the female rat fed a HF diet in the literature. METHOD: 20 female Spraque Dawley rats were used in the study. 10 of the animals were fed HF diet consisting of 30% of calories from fat for 3 months. The remaining 10 rats, the control group, were fed a normal diet. After the experimental procedure, all animals were anesthetized and omental adipose tissues in the same area were dissected and fixed for the histochemical process using a mixture of 3% glutaraldehyde and 1% osmium tetraoxide in 0.1 M phosphate buffer. After embedding of tissues in araldite CY 212, semi-thin and thin sections were cut. The semi-thin sections were stained with toluidine blue. The physical dissector counting method was used for estimation of numerical density and nuclear height of adipocytes. Cavalieri principle was used for the estimation of adipocyte volume; volume fraction approach was applied to find the volume fraction of adipose tissue components. RESULTS: The mean numerical density of adipocytes in the HF diet group was significantly higher than the control. The mean nuclear height of adipocytes was also very high in the HF diet group. The volume fraction of adipose mass was increased whereas the extracellular matrix volume fraction was reduced in the HF diet group compared to the controls. The mean volume of adipocytes in the HF diet group was also significantly higher than in the control group. At the light microscopy level, it was found that adipocytes were enlarged and gaining irregular shape in the HF diet group. Thicker basal lamina and electron dense lipid content were also found in this group at the electron microscopy level. CONCLUSION: Lipid content and number of adipocytes in the adipose tissue of HF diet rats were higher than in the controls. Thus, HF diet induces increase in body weight via both hypertrophy and hyperplasia of adipocytes.

A simple technique for localizing consecutive fields for disector pairs in light microscopy: application to neuron counting in rabbit spinal cord following spinal cord injury.

Locating the same microscopic fields in consecutive sections is important in stereological analysis. The tools for achieving this requirement have limited number in practice. This paper presents a simple and inexpensive technique for localizing the same fields on disector pairs in conventional light microscopes equipped with widely available dial indicators. It is partly a modification of equipment previously described. The presented procedure requires two light microscopes equipped with dial indicators and modified slide clips. An application of the present system was shown in a model of spinal cord injury (SCI). A midthoracic laminectomy was performed leaving the dura intact. A contusion was done at the level of midthoracic spinal cord segments (T7-T8) by dropping a 10-g mass from a height of 30 cm. The subjects were randomly divided into three groups (10 animals in each): hypothermia group, methylprednisolone group, and traumatic spinal cord injury alone group. Present results show that treatment with hypothermia after spinal cord trauma has a neuroprotective effect on cell damage but not in the methylprednisolone treatment group.

Morphological alterations produced by zinc deficiency in rat sciatic nerve: a histological, electron microscopic, and stereological study.

Zinc (Zn) is an essential trace element for humans and animals. It is required for normal growth, gene expression, wound healing, protein metabolism, immune function, and membrane integrity. In this study, unbiased stereological methods have been used to quantify the effects of Zn deficiency on the sectioned surface area and the number of myelinated axons in the sciatic nerve of rats. Animals were fed a Zn-deficient or Zn-sufficient diet for a period of 4 weeks. At the end of this time, the samples of sciatic nerves were removed from the animals, processed for electron microscopy and embedded in resin. The Zn-deficient group of rats was found to have a lower body weight compared to rats in the control group (P < 0.05). The sectioned surface area of nerve cross-section and myelinated axon number in Zn-deficient rats decreased by 20% and 29%, respectively, compared to the control group. A significant correlation between sectioned surface area and myelinated axon number was also determined. Morphological findings were as follows: on light microscopy, it was determined that certain abnormalities occur specifically in the experimental group, such as collapsed nerve fascicles, irregular profiles of and degeneration in myelin sheaths, and on electron microscopy, extensive myelin damage was seen in Zn-deficient groups compared with control groups. This study suggests that peripheral nerves require Zn for development and preservation of their structure.

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.

Estimation of numerical density and mean synaptic height in chick hippocampus 24 and 48 hours after passive avoidance training.

The effects of passive avoidance learning on synaptic morphology and number in the dorsolateral hippocampus of chick were investigated at 24 and 48 h after training. Chicks of both sexes were used. The numerical density of synapses and mean synaptic height were determined using design-based quantitative electron microscopic techniques. Our results suggest that after training there is a significant increase in synaptic density in the dorsolateral hippocampus of chicks at both 24 and 48 h, and also that the mean synaptic height was significantly different between trained and control groups. The increase in synaptic density was due to shaft (type II) synapses. It is known that during synaptogenesis, shaft synapses are formed first and are then converted to spine synapses. The only hemispheric asymmetry was found in the 24 h water-trained (W-trained) males where the numerical density of spine synapses was significantly higher in the left hippocampus. No significant differences due to gender in either numerical synaptic density or synapse height were observed at either 24 and 48 h. Comparison of the 24 h with 48 h groups showed an increase in shaft synaptic density over time in the W-trained groups, and an increased density of both shaft and spine synapses with time in methylanthranilate-trained (MeA-trained) chicks. These results demonstrate that the dorsolateral hippocampus of the chick shows synaptic changes at both 24 and 48 h after training and implicates this region in the long-term memory process.

Anti-inflammatory effect of erythromycin on histamine-induced otitis media with effusion in guinea pigs.

In this study, the anti-inflammatory effect of erythromycin was investigated in a model of histamine-induced otitis media with effusion (OME). OME was induced in guinea pigs by the transtympanic injection of histamine solution into the middle-ear cavity. Guinea pigs were randomly assigned to one of three groups: control, erythromycin treatment, or methylprednisolone treatment. After histamine injection, the animals were treated with intraperitoneal medication for five days consecutively. Afterwards, the animals were sacrificed and the temporal bones were removed. The samples were examined stereologically. In the erythromycin-treated group, it was observed that neutrophil infiltration was significantly inhibited when compared to the control group. This result shows that erythromycin may produce a significant anti-inflammatory effect in this model of OME.

Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced acute liver toxicity in rats.

Paracetamol is one of the first rank drugs which cause hepatic damage during drug intoxications. Endothelin (ET) which is known as one of the most potent vasoactive agent has been shown to contribute in the pathophysiology of various diseases. We hypothesized that bosentan, which is a non-selective ET-1 receptor antagonist, can prevent liver damage. This study included 49 female rats. Groups; I: Healthy group, II: Paracetamol (2 g/kg orally). Groups 3, 4 and 5 received NAC 140 mg/kg (2 doses), BOS 45 mg/kg and BOS 90 mg/kg orally, respectively. 1 h after administration of pretreatment drugs, Groups 3, 4, 5 were given paracetamol. VI: received BOS 90 mg/kg. VII: received 140 mg/kg NAC (2 doses). According to biochemical results, TNF-α, ALT and AST levels were statistically increased in the paracetamol group, these parameters were improved in the bosentan groups. Paracetamol administration decreased SOD activity, GSH level and increased level of MDA in the liver, while bosentan administration significantly improved these parameters. In immunohistochemical staining ET-1 receptor expression was excessively increased in paracetamol group, but not in bosentan groups when compared to healthy control. All these results suggest that bosentan exerted protective effects against experimentally induced paracetamol toxicity in liver.

A new hypothesis about hematopoietic Pbx-interaction protein (HPIP): can it be a key factor in neurodegeneration in the post-menopausal period?

Neuronal degeneration in the post-menopausal term leads to cognitive symptoms such as anxiety, difficulty in concentrating, overreacting to minor upsets, quickly becoming irritated and forgetfulness in approximately 70-80% of all women around the world. These symptoms, which result from microtubule damage in the axon extensions of hippocampal neurons in during menopause, greatly reduce individuals' life quality. Thus, an investigation of the estrogen receptor-signaling pathway-microtubule dynamic triangle and the possible links between them is important when it comes to explaining the possible mechanism of neurodegeneration. Hematopoietic Pbx-interaction protein (HPIP), a microtubule-binding protein, is a novel scaffolding protein. The detection of this protein on neurons represents the most important step in our hypothesis. The importance of the hypothesis is that it might provide important clues about the possible role of HPIP and its mechanism through in vivo and in vitro studies of estrogen receptors-microtubules and the HPIP triangle in terms of neuronal degeneration in the post-menopausal period. A preliminary study was performed to test the main part of our hypothesis using real-time PCR. According to the results, the mRNA expression of HPIP was found in hippocampal neurons. After the detection of this novel protein in neurons, it was observed that there were differences in the experimental groups when compared with the control group relating to the mRNA expression of this protein. An important scientific question remains concerning the mechanisms of neurodegeneration appearing in the post-menopausal period and the receptors, proteins, and signaling pathways that play a role in this degeneration. In consideration of the data from in vivo and in vitro studies used to test our hypothesis, we will try to address the relevant questions. As this issue is resolved, new studies and treatment procedures that can help to prevent the possible difficulties in the menopausal period will be illuminated.