The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion.

BACKGROUND: Renal injury is an important complication of infrarenal aortic occlusion (IAO), which is mainly encountered during the postoperative period. Aortic clamping procedure may lead to turbulent blood flow and eventually vasoconstriction at renal arterial level of the abdominal aorta. IL-18BP has well-known antioxidant and anti-inflammatory properties. In this study, we aimed to determine whether IL-18BP has anti-inflammatory, antiapoptotic, antioxidant, and protective effects on acute kidney damage induced by IAO rat model. MATERIALS AND METHODS: A total of 30 adult male Wistar-Albino rats were equally and randomly separated to three groups as follows: SHAM laparotomy, ischemia-reperfusion (IR), and IR + IL-18BP. We applied 30-min IAO and 2-h reperfusion. Inflammatory cytokine levels (TNF-α, IL-1ß, IL-18, IL-6, and IFN-γ) and oxidative stress parameters (TAS, TOS, and OSI) were measured. In addition to this, urea and creatinine levels, histopathology of kidney, mRNA expression levels of inflammatory cytokines, and apoptotic genes were investigated. RESULTS: Urea and creatinine, tissue and serum levels of TNF-α, IL-6, IL-18, IFN-γ, and TOS, and oxidative stress index (OSI) were found significantly lower in IR + IL-18BP group, when compared to the IR group. Moreover, mRNA expression levels of inflammatory cytokines and apoptotic genes were prominently depressed in IR + IL-18BP pre-treatment group in histopathologic examination, there was a significant difference between the IR and other three groups (P < 0.001). These improvements were demonstrated with a total score of histopathologic damage. In our previous studies, we have demonstrated that IL-18BP has antioxidant, inflammatory, and protective effects on liver and spinal cord IR injury. Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats, and this would be the first study to be conducted in this field. CONCLUSIONS: Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats.

Determining the morphometry and variations of the confluens sinuum and related structures via a silicone painting technique on autopsy patients.

In this study, we aimed to investigate the morphometric and morphologic structures of the confluens sinuum (CS) and related structures with a silicone painting technique. We studied 30 cadavers. Twelve of them were washed with alcohol and filled with a silicone painting technique via the vena jugularis interna, internal carotid artery, and vertebral artery. The other 18 were autopsied postmortem. The CS and related structures were dissected under microscope. Their anatomy was investigated, and variations were noted. The diameters of the sinus sagittalis superior (SSS), CS, occipital sinus (OS), sinus rectus (SR), and bilateral transverse sinus (TS), and the angle between SSS and SR were measured. The mean diameters were 11.7 mm for SSS, 22.3 mm for CS, 5.25 mm for OS, 7.5 mm for SR, and 9.7 (right) and 9.1 mm (left) for TS. The angle between the SR and SSS was 58°. There was no difference in the bilateral venous structures that drained to the SSS and TS. There was an extra drainage to the CS from the left side in 4 cases. The right TS was located superiorly in 7 cases compared with the left TS, and this process was correlated with the type of CS. A septum in the SSS was detected in 2 cases. In addition, we encountered an OS in 80% of the cases. We conclude that the septum inside the CS affects the dominancy of the TS, the angle between the SSS and SR, and the other venous variations.

Morphometry, asymmetry and variations of cerebral sulci on superolateral surface of cerebrum in autopsy cases.

BACKGROUND: The cerebral sulci are known as main microanatomical borders that serve as a gateway and surgical passage to reach the ventricles or to the deeper lesions. It is a matter of curiosity that whether there is a convergence between the morphological asymmetry and the functional asymmetry, and also its significance in surgery. The aim of this study is make morphometric measurements and evaluate asymmetry of several sulci on the lateral aspects of the cerebrum in regard to main sulci and related reference key points. METHODS: A total of 100 cerebral hemispheres from 50 autopsy cadavers were examined. The lengths of several sulci on the superolateral aspect of the hemispheres and the distances between the sulci and nearby sulci and the reference key points were measured. Encountered variations were examined and photographed. RESULTS: Evaluation of the variations: superior frontal sulcus (SFS), inferior frontal sulcus, superior temporal sulcus (STS), precentral sulcus and postcentral sulcus were found to be discontinuous in 60, 46, 41, 84 and 70 % of the hemispheres, respectively. Evaluation of the asymmetry: the distances between SFS posterior end and longitudinal fissure, STS posterior end and lateral sulcus posterior end, as well as lengths of external occipital fissure (EOF), and discontinuous course of STS were significantly different between left and right hemispheres. CONCLUSIONS: There is usually a morphological partial asymmetry between the right and left hemispheres for any individual. Also, some of our measurements were found to be compatible with the ones in the literature, while others were incompatible.

Age-related volumetric changes in pancreas: a stereological study on computed tomography.

PURPOSE: (1) To explore age-related changes in the volume of the pancreas on computed tomography (CT) images calculated by the method of Cavalieri. (2) To investigate the relationship between these changes and body mass index (BMI), gender, abdominal diameter, abdominal skinfold thickness. METHODS: We retrospectively reviewed abdominal CT examinations of 272 adults between the ages of 20-88 years. There were seven groups of patients, with 40 patients (only ninth decade has 32 patients) for each decade. RESULTS: Pancreatic volume (PV) was found to be 63.68 ± 15.08 cm(3) in females, 71.75 ± 15.99 cm(3) in males (mean value of both groups, 67.71 ± 16.03 cm(3)). Maximum value of PV was found in the fourth decade in females, males and also for mean of both groups (73.50, 84.21 and 78.85 cm(3), respectively). PV remained constant until ~60 years of age. Thereafter, it gradually decreased in both genders. There was a negative correlation between PV and age (p < 0.001, r: -0.473). We found positive correlation between PV and BMI, sagittal abdominal diameter (SAD), transverse abdominal diameter (TAD), anterior subcutaneous adipose tissue thicknesses (ASAT), posterior subcutaneous adipose tissue thicknesses (PSAT), bilateral subcutaneous adipose tissue thicknesses (BSAT). CONCLUSIONS: Quantitative data may allow clinicians to better estimate age-related PV changes and help them in decision making.

The protective effect of avocado soybean unsaponifilables on brain ischemia/reperfusion injury in rat prefrontal cortex.

OBJECT: We investigated the protective effects of avocado/soybean unsaponifiables (ASU) on the prefrontal cortex (PFC) after global brain ischemia/reperfusion (I/R) injury in rats. METHODS: Rats were randomly divided into three experimental groups as follows: Group I was control rats, Group II was ischemia rats, Group III was Isch + ASU rats. Brain ischemia was produced via four-vessel occlusion model. These processes followed by reperfusion for 30 min for both II and III groups. Rats were sacrificed and their brains were removed immediately. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in left PFC, levels of TNF-α concentration were measured in the plasma. The number of apoptotic neurons was assayed in histological samples of the right PFC. RESULTS: MDA and TNF-α levels as well as the number of apoptotic neurons were observed to have decreased significantly in Group III compared to Group II, while SOD activities have been found to have increased significantly in Group III in comparison to Group II, significantly. CONCLUSIONS: We think that ASU might have an antioxidant and neuroprotective effects in brain I/R injured rats.

Protective effects of omega-3 essential fatty acids against formaldehyde-induced cerebellar damage in rats.

This study aimed to investigate changes in the cerebellum of formaldehyde-exposed rats and the effects of omega-3 fatty acids on these changes. The study involved 21 male Wistar-Albino rats which were divided into three groups. The rats in Group I comprised the control group. The rats in Group II were injected with intraperitoneal 10% formaldehyde every other day. The rats in Group III received omega-3 fatty acids daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation and the cerebellum removed. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), and malondialdehyde (MDA) levels were determined in cerebellum specimens by using spectrophotometric methods. In our study, levels of SOD and CAT were significantly decreased, and GSH-Px, XO, MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Whereas, it was seen that there was an increase in SOD and CAT enzyme activities and decrease in MDA, XO, and GSH-Px levels in rats administered to omega-3 fatty acids with exposure of formaldehyde. It was determined that exposure of formaldehyde increased free radicals in cerebellum of rats and this increase was prevented by administration of omega-3 fatty acids.

The toxic effects of formaldehyde on the nervous system.

Formaldehyde (FA) is found in the polluted atmosphere of cities, domestic air (e.g., paint, insulating materials, chipboard and plywood, fabrics, furniture, paper), and cigarette smoke, etc.; therefore, everyone and particularly susceptible children may be exposed to FA. FA is also widely used in industrial and medical settings and as a sterilizing agent, disinfectant, and preservative. Therefore, employees may be highly exposed to it in there settings. Of particular concern to the authors are anatomists and medical students, who can be highly exposed to formaldehyde vapor during dissection sessions. Formaldehyde is toxic over a range of doses; chances of exposure and subsequent harmful effects are increased as (room) temperature increases, because of FA's volatility. Many studies have been conducted to evaluate the effects of FA during systemic and respiratory exposures in rats. This review compiles that literature and emphasizes the neurotoxic effects of FA on neuronal morphology, behavior, and biochemical parameters. The review includes the results of some of the authors' work related to FA neurotoxicity, and such neurotoxic effects from FA exposure were experimentally demonstrated. Moreover, the effectiveness of some antioxidants such as melatonin, fish omega-3, and CAPE was observed in the treatment of the harmful effects of FA. Despite the harmful effects from FA exposure, it is commonly used in Turkey and elsewhere in dissection laboratories. Consequently, all anatomists must know and understand the effects of this toxic agent on organisms and the environment, and take precautions to avoid unnecessary exposure. The reviewed studies have indicated that FA has neurotoxic characteristics and systemic toxic effects. It is hypothesized that inhalation of FA, during the early postnatal period, is linked to some neurological diseases that occur in adults. Although complete prevention is impossible for laboratory workers and members of industries utilizing FA, certain precautions can be taken to decrease and/or prevent the toxic effects of FA.

The influence of dexmedetomidine on ischemic rat hippocampus.

In our study, we evaluated the neuroprotective effects of dexmedetomidine on oxidant-antioxidant systems, pro-inflammatory cytokine TNF-alpha and number of apoptotic neurons on hippocampus and dentate gyrus after transient global cerebral I/R injury. Eighteen rats divided into 3 groups, equally. Group I rats were used as shams. For group II and III rats, they were prepared for transient global cerebral ischemia using a four-vessel-occlusion model. 5 mL/kg/h 0.9% sodium chloride was infused to the Group II and 3 microg/kg/h/5 ml dexmedetomidine was infused to the Group III for 2 h after I/R injury. The levels of MDA and NO and activities of SOD and CAT were measured in the left hippocampus tissue. The levels of TNF-alpha concentration were measured in the plasma. The number of apoptotic neurons was counted by TUNNEL method in histological samples of right hippocampus tissue. MDA and NO levels increased in Group II compared with Group I rats (p=0.002, p=0.002, respectively). In group III, MDA and NO levels decreased as compared to Group II (p=0.015, p=0.002, respectively). SOD and CAT activities increased in Group III as compared to Group II rats (p=0.002, p=0.002, respectively). The decrease in TNF-alpha levels of group III was significant as compared to group II (p=0.016). The number of apoptotic neurons in group III was lower than Group II rats. Our study showed that dexmedetomidine has a neuroprotective effect on hippocampus and dentate gyrus of rats after transient global cerebral I/R injury.

The neuroprotective effect of fish n-3 fatty acids in the hippocampus of diabetic rats.

INTRODUCTION: Diabetes mellitus may lead to functional and structural changes in the brain. Fish oil is a rich source of n-3 essential fatty acids (EFA) such as eicosapentaenoic and docosahexoenoic acids. We examined the neuroprotective effects of fish n-3 EFA in the hippocampus of diabetic rats. MATERIALS AND METHODS: Nineteen adult male rats were divided into three groups. Group I (control; n = 6) was fed a normal rat diet. Group II (diabetic; n = 6) was fed a normal rat diet and streptozotocin (STZ) was administered to induce diabetes mellitus. Group III (n-3 + diabetic; n = 7) was fed a normal rat diet and fish n-3 EFA (Marincap, 0.4 g/kg/day) for 8 weeks and STZ was administered to induce diabetes mellitus. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in the left hippocampus after the animals were sacrificed. The right hemisphere was completely blocked. The sections were stained with Cresyl Violet and apoptotic neurons were counted in the hippocampus. RESULTS: The levels of MDA and activities of SOD and CAT increased in diabetic rats compared to control rats. However, the levels of MDA and activities of SOD and CAT decreased in n-3 + diabetic rats compared to diabetic rats. Also, the number of apoptotic neurons increased in diabetic rats compared to control rats and decreased in n-3 + diabetic rats compared to diabetic rats. CONCLUSIONS: Fish n-3 EFA reduces oxidative stress and induces apoptotic changes in the hippocampus of STZ-diabetic rats. The addition of fish n-3 EFA to diets may be useful to prevent functional and structural changes to cerebral centers due to diabetes mellitus.

Basilar artery angulation and vertigo due to the hemodynamic effect of dominant vertebral artery.

Vertebral arteries form the basilar artery at the pontobulbar junction. The vertebral artery may have dominancy in one of them. The branches of basilar arteries supply blood for the vestibular nuclei and its connections. Vertigo is seen generally in the upper middle aged patients. Vertigo can be observed in dolichoectasia of basilar artery such as angulation and elongation, because of the diminished blood supply and changed hemodynamic factors of vestibular nuclei and its connections. We hypothesized that angulation or elongation of basilar artery can be estimated according to the unilateral vertebral artery dominant hypertensive patients. The basilar artery can angulate from the dominant side of vertebral artery to the recessive side. These angulation and elongation can effect the hemodynamic factors in absence of growing collateral arteries. So, the vertigo attacks may occur in these patients.

Talonavicular joint approach to the talar body: a cadaver study.

BACKGROUND: Lesions of the talar dome or tumors within the talar body may require an open approach with medial or lateral malleolar osteotomies. The aim of this study was to evaluate the possibility and feasibility of a new minimally invasive approach without osteotomy, using the talonavicular joint (TJ) as the entry portal for lesions of the talar body. MATERIALS AND METHODS: Nine cadaveric feet were used for this study. Using the TJ and a 5-mm skin incision we aimed to reach the superolateral, superomedial, inferolateral and inferomedial corners of the talar body under fluoroscopy. A 2-mm Kirshner wire and a 4-mm cannulated drill bit were used to reach the desired target area and an angled curette was used for curettage after reaching the target. The proximity of vascular structures to the entry portal was noted. The talar and navicular joint surfaces were checked for any damage. The articular areas of the talar heads and the defect areas were measured. RESULTS: All 4 targets and even the posterior talus could be reached by this approach. The nearest neurovascular structures were the saphenous vein and the saphenous nerve. The navicular cartilage was not damaged in any specimen. The talar defect area corresponded to only 3.3% of the talar head cartilaginous area. CONCLUSION: The TJ approach can be used to reach lesions in all regions of the talar body without the need for an osteotomy. A mini-incision may be used to retract the saphenous nerve and vein. Damage to the talar head cartilage is minimal with this approach which requires no special equipments. CLINICAL RELEVANCE: This study shows that talar dome lesions can be reached with a minimally invasive method.

The effects of inhaled formaldehyde on oxidant and antioxidant systems of rat cerebellum during the postnatal development process.

ABSTRACT The aim of this study was to examine the effects of formaldehyde (FA) inhalation during the early postnatal period on some oxidant and antioxidant systems of rat cerebellum in the developmental process and to determine whether the changes were reversible or not. After birth, 0 (control), 6, or 12 ppm FA5 was given to the neonatal rats throughout 30 days. This was done by placing them for 6 h/day and 5 day/week in a glass chamber containing FA vapor. After cessation of the FA exposing process, seven rats from each group were decapitated on postnatal day (PND) 30 and the remaining seven rats were decapitated on the PND 90, and all cerebellums were removed immediately. On samples, levels of malondialdehyde (MDA) and nitric oxide (NO) and activities of total superoxide dismutase (t-SOD) and glutathione peroxidase (GSH-px) enzymes were measured. We found that activity of GSH-Px and levels of MDA and NO increased; on the other hand, activity of t-SOD decreased significantly in the rats treated with FA compared to control rats at PND 30. In general, the findings at PND 90 were similar to PND 30. Additionally, we observed that the 12-ppm FA-inhaling rats were more affected than the 6-ppm FA-inhaling rats, especially at PND 30. As a result, the present findings suggest that inhalation of FA during the early postnatal period affects the oxidant and antioxidant systems and increases some free radicals in the rat cerebellum in a dose-related manner. We think that these changes were carried on for a long time or may cause irreversible toxicity and oxidative damage.

Oedema risk of endotracheal intubation in rabbits with cessation of steroid therapy.

Rebound oedema of tissues is a well defined complication of cessation of steroid therapy. Tapering of systemic corticosteroid regimens in short course steroid therapy is considered unnecessary in most circumstances in acute exacerbation of chronic obstructive pulmonary diseases, presence of laryngeal rebound edema is obscure in this situation. We studied whether or not laryngeal oedema increases after intubation when intubation is established after cessation of steroid therapy. Thirty-six rabbits were randomly divided into six groups. We administered 1 mg/kg methyl prednisolone intraperitoneally to four steroid groups for ten days. Another group received serum physiologic for ten days and last group was sham control that was intubated only. Rabbits that received steroid therapy were intubated and separated into groups one day, one week, two weeks, and a month after the cessation of steroid therapy. Airway area and percentage of cross sectional area of larynx lumen to their own larynx tissues surrounded by thyroid cartilage and oesophagus were studied by stereological methods. Larynx lumen area of one week steroid group was significantly narrower and percentage of cross sectional area of larynx lumen to their own larynx tissues surrounded by thyroid cartilage and oesophagus was significantly larger than sham control. Rebound oedema forms in larynx with abrupt cessation of steroid therapy in rabbits. Clinical safe time for intubation after abrupt cessation of steroid therapy is also defined with our study. These results suggest that one week after the cessation of steroid therapy may be a hazardous time for tracheal intubation.

The protective effect of fish n-3 fatty acids on cerebral ischemia in rat hippocampus.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of cerebral injury after ischemia-reperfusion (I/R). Fish n-3 essential fatty acids (EFA), contain eicosapentaenoic acids (EPA) and docosahexoenoic acids (DHA), exhibit antioxidant properties. DHA is an important component of brain membrane phospholipids and is necessary for the continuity of neuronal functions. EPA prevents platelet aggregation and inhibits the conversion of arachidonic acid into thromboxane A(2) and prostaglandins. They have been suggested to be protective agents against neurological and neuropsychiatric disorders. In this study, the neuroprotective effects of fish n-3 EFA on oxidant-antioxidant systems and number of apoptotic neurons of the hippocampal formation (HF) subjected to cerebral I/R injury was investigated in Sprague-Dawley rats. Six rats were used as control (Group I). Cerebral ischemia was produced by occlusion of both the common carotid arteries combined with hypotension for 45 min, followed by reperfusion for 30 min, in rats either on a standard diet (Group II) or a standard diet plus fish n-3 EFA (Marincap((R)), 0.4 g/kg/day, by gavage) for 14 days (Group III). At the end of procedures, the rats were sacrificed and their brains were removed immediately. The levels of malonedialdehyde (MDA) and nitric oxide (NO) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in left HF. In addition, the number of apoptotic neurons was counted by terminal transferase dUTP nick end labelling (TUNEL) assay in histological samples of the right HF. We found that SOD activities and MDA levels increased in Group III rats compared with Group II rats. On the other hand, CAT activities and NO levels were found to be decreased in Group III rats compared with Group II rats. Additionally, the number of apoptotic neurons was lower in Group III in comparison with Group II rats. The present findings suggest that fish n-3 EFA could decrease the oxidative status and apoptotic changes in ischemic rat hippocampal formation. Dietary supplementation of n-3 EFA may be beneficial to preserve or ameliorate ischemic cerebral vascular disease.

Effects of postnatal formaldehyde exposure on pyramidal cell number, volume of cell layer in hippocampus and hemisphere in the rat: a stereological study.

The purpose of the present study was to determine whether exposure of neonatal rats to formaldehyde (FA) had either early or delayed effects on the numbers of pyramidal cells in the cornu ammonis (CA) of the hippocampus. Neonatal Wistar rats were exposed to 0 ppm (control group), 6 ppm and 12 ppm (high concentration group) of FA concentrations throughout the 30-day period following the birth by placing them for 6 h/day in a glass chamber containing FA vapor. Then, some of the animals from each FA-treated group were anesthetized and decapitated at the day 30, and the remaining ones were killed at the day 90. The brains were removed immediately and fixed in 10% neutral-buffered FA solution. The Cavalieri principle was used to determine the volumes of the CA and the entire cerebral hemisphere. The optical fractionator counting method was used to estimate the total number of pyramidal cells in the CA. The appearance of pyramidal cells was normal under light microscopy at both postnatal day (PND) 30 and PND 90 in all groups. There were concentration-related volume changes of CA at PND 30 and PND 90; low concentration of FA significantly increased, whereas high concentration decreased the volume of CA in comparison of the control at PND 30. Importantly, high concentration of FA at PND 90 increased the volume of CA in comparison of the low concentration but not with the control. Furthermore, low and high concentrations of FA decreased the volume of hemisphere at PND 30, whereas a reverse effect of these concentrations was observed at the hemisphere of PND 90 in comparison of the control. In both CA and cerebral hemisphere, an age-related volume decrease in both control and low/high concentration groups were found. On the other hand, there were significant age-related reductions in the total number of pyramidal cells at 90 days of age irrespective of the groups examined. Rats treated with high concentration FA were seen to have significantly fewer pyramidal cell neurons than either the animals treated with low concentration FA or control groups (p<0.01). These observations indicate that pyramidal cells in the hippocampus may be vulnerable to FA exposure during the early period of life.

Oral administration of avocado soybean unsaponifiables (ASU) reduces ischemic damage in the rat hippocampus.

BACKGROUND: The beneficial effects of avocado/soybean unsaponifiables (ASU) are known as an antiarthritic agent. This experimental study presents the effects of ASU on oxidant/antioxidant systems and the number of apoptotic neurons of hippocampal formation after ischemia and reperfusion. METHODS: Eighteen rats were divided into three equal groups: group I rats were used as controls; group II rats were fed with standard diet and group III rats were fed with standard diet plus ASU pills for 10 days. One day after electrocauterization of bilateral vertebral arteries for groups II and III, bilateral common carotid arteries were occluded for 30 min and then reperfused for 30 min. After these procedures, rats of all groups were sacrificed. The levels of malondialdehyde (MDA) and nitric oxide (NO) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in the left hippocampus. The number of apoptotic neurons was counted by Tunel method in histological samples of right hippocampus. RESULTS: MDA and NO levels increased in group II compared with group I rats (p = 0.002, p = 0.015). In group III, MDA and NO levels decreased as compared to group II (p = 0.041, p = 0.002). SOD and CAT activities increased in group III as compared to group II rats (p = 0.002, p = 0.002). The number of apoptotic neurons was lower in group III as compared to group II rats. CONCLUSIONS: The present findings suggest that ASU could decrease oxidative stress and apoptotic changes in ischemic rat hippocampus. Dietary supplementation of ASU may be beneficial to prevent or ameliorate ischemic cerebral vascular disease.

Protective effects of erdosteine on doxorubicin-induced hepatotoxicity in rats.

BACKGROUND: Oxidative stress has an important role in the pathogenesis of doxorubicin-induced hepatotoxicity. The aim of this study was to investigate the hepatoprotective effects of erdosteine, an antioxidant agent, on doxorubicin-induced hepatotoxicity. METHODS: Rats were divided into control, doxorubicin alone (20 mg/kg, i.p.) and doxorubicin plus erdosteine (50 mg/kg/day, oral) groups. At the end of the 10(th) day, liver tissues were removed for light microscopy and analysis. The levels of tissue protein carbonyl content, malondialdehyde and nitric oxide, as well as the activities of superoxide dismutase, catalase, were determined. RESULTS: The tissue of the doxorubicin group showed some histopathological changes such as necrosis, hepatocyte degeneration, sinusoidal dilatation, hemorrhage and vascular congestion and dilatation. In the doxorubicin plus erdosteine group, histopathological evidence of hepatic damage was markedly reduced. Biochemical parameters were consistent with histological parameters. CONCLUSIONS: Doxorubicin caused hepatotoxicity, and erdosteine treatment prevented lipid peroxidation and protein oxidant in liver tissue.

The neuroprotective effects of caffeic acid phenethyl ester (CAPE) in the hippocampal formation of cigarette smoke exposed rabbits.

BACKGROUND: In this study, the neuroprotective effects of caffeic acid phenethyl ester (CAPE) in the hippocampus of cigarette smoke exposed rabbits were investigated. MATERIALS AND METHODS: Eighteen rabbits were used as experimental subjects and divided into three equal groups. The control group (Group A) was exposed to clean air. Rabbits in the cigarette smoke (CS) group (Group B) were exposed to cigarette smoke 1 hour daily in a room within a glass chamber for 4 weeks. Animals in the CS+CAPE group (Group C) were exposed to cigarette smoke as in Group B and administered CAPE (10 micromol/kg/day) intraperitoneally for 4 weeks just before the exposure to cigarette smoke. Rabbits in all three groups were sacrificed with intraperitoneal administration of 100 mg/kg sodium pentothal and their brains were removed immediately. In the hippocampal formation samples of left hemispheres, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured and the number of apoptotic neurons was counted by 'terminal transferase dUTP nick end labelling' (TUNEL) assay in the right hippocampal formation. RESULTS: We found that MDA levels increased significantly in the Group B rabbits compared with the control group (Group A; p = 0.001). In contrast, SOD activities decreased significantly in Group B rabbits compared with the control group (p = 0.001). In the CAPE treated rabbits (Group C), MDA levels decreased and SOD activities increased significantly as compared with Group B rabbits (p = 0.002, p = 0.002, respectively). The number of apoptotic neurons (TUNEL+) in the CA1, CA2, CA3 and dentate gyrus areas of rabbits' hippocampal formation were significantly increased in Group B rabbits compared with the control group. On the other hand, the number of apoptotic neurons in the hippocampus areas was decreased significantly in Group C rabbits compared with Group B rabbits. CONCLUSION: These findings suggest that cigarette smoking induces apoptosis in the hippocampal formation of rabbits and CAPE has a protective role against this induction.

Effects of formaldehyde exposure on granule cell number and volume of dentate gyrus: a histopathological and stereological study.

The hippocampal formation is a complex region of the brain related to memory and learning. The purpose of the present study was to determine whether exposure of neonatal rats to formaldehyde (FA) had either early or delayed effects on the numbers of granule cells in the dentate gyrus (DG). After birth, the neonatal male Wistar rats were exposed throughout a 30-day period to various concentrations of FA: 0 (control group), 6 ppm (low concentration group) and 12 ppm (high concentration group). This was done by placing them for 6 h/day and 5 days per week in a glass chamber containing FA vapor. Then, five animals from each group were anesthetized and decapitated on postnatal day (PND) 30, and the remaining five animals were sacrificed on PND 90 by intracardiac perfusion using 10% neutral buffered FA solution. The Cavalieri principle of stereological approaches was used to determine the volume of the DG in these sections. The optical fractionator counting method was used to estimate the total number of granule cells in the DG. The appearance of granule cells was normal under light microscopy in all PND 30 and PND 90 groups. There were significant age-related reductions in the volume of the DG at PND 90 irrespective of which group was examined. Significant age-related neuron loss was also determined at PND 90 compared to that at PND 30. Rats treated with a high concentration FA were found to have fewer granule cells than either the animals treated with a low concentration FA or the control group (p<0.01 and p<0.01, respectively) at PND 90 but not at PND 30. These findings clearly indicate that granule cells in the DG may be vulnerable to stress and the concentration of FA to which they are exposed during early postnatal life, and also that a neurotoxic effect of high dose FA on cell number is only seen after a long time period. These results may explain why some disorders do not appear until later life.

The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: protective effect of caffeic acid phenethyl ester.

The aim of this experimental study was to investigate the possible role of nitric oxide (NO) levels and activity of adenosine deaminase (ADA) in the pathogenesis of methotrexate (MTX)-induced neurotoxicity, to demonstrate the effect of caffeic acid phenethyl ester (CAPE), the potent antioxidant, in decreasing the toxicity. A total of 19 adult male rats were divided into three experimental groups, as follows: group I, control group; group II, MTX-treated group; group III, MTX+CAPE-treated group. In the second day of experiment, MTX was administered intraperitoneally (i.p.) with a single dose of 20mg/kg to group II and group III. CAPE was administered i.p. with a dose of 10 micromol/kg once daily for 7 days to group III. Histopathological findings of the inflammatory reaction were observed in spinal cord of MTX administered rats, compared with control rats. All parameters of inflammatory reaction were significantly decreased in MTX plus CAPE administered rats, compared with MTX administered rats. The injection of MTX caused significant increase in the activity of ADA and in levels NO levels in spinal cord of rats (p=0.007 and p=0.0001, respectively). Co-treatment with CAPE caused a significant decrease in activity of ADA and the levels of NO in spinal cord (p=0.024 and p=0.0001, respectively). Study indicate that NO and ADA may play an important role in the pathogenesis of MTX-induced oxidative spinal cord damage. CAPE may have protective aspects in this process by antioxidant and anti-inflammatory effect and it will become a promising drug in the prevention of undesired side effect of MTX.