Electron microscopic investigation of benzo(a)pyrene-induced alterations in the rat kidney tissue and the protective effects of curcumin.

Benzo(a)pyrene (BaP) is a polycyclic hydrocarbon with carcinogenic and DNA damaging properties. Curcumin, primary yellow pigment in turmeric, has a wide range of biological, pharmacological properties in addition to being a powerful antioxidant. The aim of this study was to investigate protective effects of curcumin against benzo(a)pyrene damage in rat kidney. Thirty-six male Wistar albino rats were divided into six groups (n = 6) as: control, corn oil, Dimethyl sulfoxide (DMSO), BaP (10 mg/kg/day), Curcumin (100 mg/kg/day), Curcumin+BaP (100 mg/kg/day+10 mg/kg/day). Agents were daily and orally administered for six weeks. Kidney tissues were removed and examined ultrastructurally. Glomerular and tubular structures in control, corn oil, and DMSO groups demonstrated normal features. Glomerular capillary dilation, thickening, and folding of basement membrane and disruption of organelle contents were distinguished in BaP group. Deletion of podocyte cell and pedicels also sponge-like appearance of glomerular surface were remarkable in this group. Tissue components were protected in curcumin treated group. Proximal tubules and glomerular basement membrane exhibited normal features in Curcumin+BaP group. The abnormalities that accompanied BaP administration clearly revealed the detrimental effects of this agent. Therefore, this study provided substantial evidence that curcumin protects against benzo(a)pyrene nephrotoxicity.

In Silico Analysis of Elastomer-Coated Cerclage for Reducing Sternal Cut-Through in High-Risk Patients.

BACKGROUND: AISI 316 L stainless steel wire cerclage routinely used in sternotomy closure causes lateral cut-through damage and fracture, especially in cases of high-risk patients, which leads to postoperative complications. A biocompatible elastomer (Pellethane®) coating on the standard wire is proposed to mitigate the cut-through effect. METHODS: Simplified peri-sternal and transsternal, sternum-cerclage contact models are created and statically analyzed in a finite element (FE) software to characterize the stress-reduction effect of the polymer coating for thicknesses between 0.5 and 1.125 mm. The performance of the polymer-coated cerclage in alleviating the detrimental cortical stresses is also compared to the standard steel cerclage in a full sternal closure FE model for the extreme cough loading scenario. RESULTS: It was observed via the simplified contact simulations that the cortical stresses can be substantially decreased by increasing the coating thickness. The full closure coughing simulation on the human sternum further corroborated the simplified contact results. The stress reduction effect was found to be more prominent in the transsternal contacts in comparison to peri-sternal contacts. CONCLUSIONS: Bearing in mind the promising numerical simulation results, it is put forth that a standard steel wire coated with Pellethane will majorly address the cut-through complication.

The effect of di-n-butyl phthalate on testis and the potential protective effects of resveratrol.

This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di-n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.

Examining the protective effects of acetyl l-carnitine on cisplatin-induced uterine tube toxicity.

The aim of this study was to investigate the effects of cisplatin and the protective role of acetyl l-carnitine against uterine tube toxicity. Twenty-four female Wistar albino rats were divided into four groups: control group was injected with saline (control); group 2 was injected with acetyl l-carnitine; group 3 was injected with cisplatin; and group 4 was pre-treated with acetyl l-carnitine before cisplatin intraperitoneal injection. According to our results, a significant weight loss was observed in rats from group 3. The thickness of the wall and epithelium of uterine tube were decreased in group 3 rats. We elaborate the protein expression of caspase in epithelium and stroma by IHC. We found that the expression of caspase and the number of TUNEL-positive cells were increased in group 3 rats compared to the other groups. In our study, we showed the protective role of acetyl l-carnitine against uterine tube toxicity caused by cisplatin.

Ciliary body toxicities of systemic oxcarbazepine and valproic acid treatments: electron microscopic study.

Ciliary body is responsible for humour aqueous production in posterior chamber. Valproic acid (VPA) has been widely used for the treatment of epilepsy and other neuropsychiatric diseases such as bipolar disease and major depression. Oxcarbazepine (OXC) is a new anti-epileptic agent that has been used recently for childhood epilepsies such as VPA. In this study, we aimed to investigate the effects of VPA and OXC treatments used as antiepileptic in ciliary body by electron microscopy. In our study, 40 Wistar rats (21 days old) were divided equally into four groups which were applied saline (group 1), VPA (group 2), OXC (group 3) and VPA + OXC (group 4). The as-prepared ocular tissues were characterized by transmission electron microscopy (TEM) technique in scanning and transmission electron microscopy (SEM-TEM) (Carl Zeiss EVO LS10). The results confirmed that VPA caused dense ciliary body degeneration. Additionally, ciliary body degeneration in group 4 was supposed to be due to VPA treatment. Ciliary body damage and secondary outcomes should be considered in patients with long-term VPA therapy.

The treatment of segmental bone defects in rabbit tibiae with vascular endothelial growth factor (VEGF)-loaded gelatin/hydroxyapatite "cryogel" scaffold.

The aim of this study was to investigate the effectiveness of a novel hydroxyapatite containing gelatin scaffold--with and without local vascular endothelial growth factor (VEGF) administration--as the synthetic graft material in treatment of critical-sized bone defects. An experimental nonunion model was established by creating critical-sized (10 mm. in length) bone defects in the proximal tibiae of 30 skeletally mature New Zealand white rabbits. Following tibial intramedullary fixation, the rabbits were grouped into three: The defects were left empty in the first (control) group, the defects were grafted with synthetic scaffolds in the second group, and synthetic scaffolds loaded with VEGF were administered at bone defects in the third group. Five rabbits in each group were killed on 6th and 12th weeks, and new bone growth was assessed radiologically, histologically and with dual-energy X-ray absorptiometry (DEXA). At 6 weeks, VEGF-administered group had significantly better scores than the other two groups. The second group also had significantly better scores than the control group. At 12 weeks, while no significant difference was noted between the second and third groups, these two groups both had significantly better scores in all criteria compared with the control group. There were no signs of complete fracture healing in the control group. The administration of hydroxyapatite containing gelatin scaffold yielded favorable results in grafting the critical-sized bone defects in this experimental model. The local administration of VEGF on the graft had a positive effect in the early phase of fracture healing.

Therapeutic effects of melatonin in long-term exposure to 2100MHz radiofrequency radiation on rat sperm characteristics.

INTRODUCTION: Radiofrequency electromagnetic fields (RF-EMFs) are one of the risk factors for male reproductive health and melatonin can be an ideal candidate for therapeutic development against RF-induced male fertility problems due to its antioxidant properties. The possible therapeutic role of melatonin in the destructive effects of 2100MHz RF radiation on rat sperm characteristics is investigated in the present study. METHODS: Wistar albino rats were divided into four groups and the experiment continued for ninety consecutive days; Control, Melatonin (10mg/kg, subcutaneously), RF (2100MHz, thirty minutes per day, whole-body), and RF+Melatonin groups. Left caudal epididymis and ductus deferens tissues were placed in sperm wash solution (at 37°C) and dissected. The sperms were counted and stained. Measurements of the perinuclear ring of the manchette and posterior portion of the nucleus (ARC) were performed and the sperms were examined at an ultrastructural level. All of the parameters were evaluated statistically. RESULTS: The percentages of abnormal sperm morphology were significantly increased with RF exposure, while the total sperm count was significantly decreased. RF exposure also showed harmful effects on acrosome, axoneme, mitochondrial sheath, and outer dense fibers at the ultrastructural level. The number of total sperms, sperms with normal morphology increased, and ultrastructural appearance returned to normal by melatonin administration. DISCUSSION: The data showed that melatonin may be a beneficial therapeutic agent for long-term exposure of 2100MHz RF radiation-related reproductive impairments.

A new voltammetric method for the determination of lercanidipine in biological samples.

Electrochemical behavior and adsorption-diffusion properties of lercanidipine (LCN) on a glassy carbon electrode (GCE) were investigated in a mixture of ethanol-Britton Robinson buffer (BR) using voltammetric methods. From experimental results LCN was found to be reduced irreversibly via a single four-electron process controlled mainly by diffusion with some adsorption contribution at about -0.65 V (vs. Ag/AgCl reference electrode). Therefore, a new, accurate, rapid, selective and simple square-wave cathodic adsorptive stripping voltammetric (SWCAdSV) method could be developed for direct determination of LCN in pharmaceutical preparations, spiked human urine and spiked human serum samples without time-consuming steps prior to drug assay. The peak current of the reduction wave linearly changed with the concentration of LCN in the concentration range between 4.0 × 10-8 molL-1 and 7.6 × 10-6 molL-1 in two different regions where optimum preconcentration potential and optimum preconcentration time were applied as -0.20 V and 90 s, respectively. The limit of detection (LOD) and the limit of quantitation (LOQ) values were found to be 2 × 10-8 molL-1 (0.01 mgL-1) and 6 × 10-8 molL-1 (0.04 mgL-1), respectively. The method was applied to determine the content of LCN in commercial pharmaceutical preparation, spiked human serum and spiked human urine. The method was found to be highly accurate and precise, having a relative standard deviation of less than 10% in all applications.

Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells.

PURPOSE: To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells. METHODS: Fifty-six female prepubertal Wistar rats (21-24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques. RESULTS: In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 +/- 1.32 in controls, and significantly increased to 29.60 +/- 1.58, 34.20 +/- 2.53, and 54.80 +/- 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group. CONCLUSION: VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.

An immunohistochemical study of the effects of various antioxidants on rat lung during chemotherapy.

We investigated using immunohistochemistry the possible protective effects of ascorbic acid, α-tocopherol and selenium during chemotherapy treatment with cyclophosphamide. Thirty female Wistar rats were divided into five groups of six: group 1, untreated control; group 2, 75 µg/kg cyclophosphamide; group 3, 75 µg/kg cyclophosphamide + 150 µg/kg/day α-tocopherol; group 4, 75 µg/kg cyclophosphamide + 200 µg/kg/day ascorbic acid and group 5, 75 µg/kg cyclophosphamide + 40 ppm/kg/day selenium. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and AT1 was used to evaluate structural damage. Caspase-8, caspase-9 and caspase-3 signal molecules were used to investigate apoptosis. In group 2, epithelium, alveolar macrophages, infiltrated lymphocytes and connective tissue were immunostained moderately to strongly with PCNA. Bronchus, alveolar wall and infiltrated lymphocytes were immunostained moderately to strongly with AT1 and diffuse strong caspase immunoreactions were observed throughout the lung tissue. AT1 and caspase immunoreactions in groups 4 and 5 were similar to group 2. In group 3, PCNA immunoreactivity was strong in the bronchiolus epithelium, endothelial cell nuclei and in stacks of infiltrated lymphocyte cell nuclei. In group 3, AT1 and caspase immunoreactions were identical to group 1. It appears that α-tocopherol inhibits lung tissue damage in rats during chemotherapy.

Effect of a chloride channel inhibitor, 5-nitro-2- (3-phenylpropylamino)-benzoate, on endothelin-1 induced vasoconstriction in rabbit basilar artery.

AIM: Endothelin-1 (ET-1) has been implicated in the pathophysiology of cerebral vasospasm. Chloride (Cl-) channels exist in vascular smooth muscle and activation of these channels leads to depolarization and contraction. The aim of the present study was to test the effect of 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel antagonist, on the ET-1-induced cerebral vasospasm in rabbit basilar artery and thus investigate the contribution of Cl- channels. MATERIAL AND METHODS: Thirty rabbits were divided into five groups and received intra-arterial injection of isotonic saline (Group I, n=6), ET-1 (group II, n=6), ET-1 plus NPPB (Group III, n=6), dimethylsulfate (DMSO4) (Group IV, n = 6) and NPPB (Group V, n=6). Pre and post injection basilar artery diameters were measured in each group and transmission electron microscopic investigations on basilar arteries were performed. RESULTS: The mean pre-injection and post-injection vessel diameters were 0.8833 mm and 0.7000 mm in ET-1 group, 0.6833 mm and 0.8500 mm in ET-1 + NPPB group. NPPB administered prior to ET-1 injection, prevented the ET-1-induced vasoconstriction. Additionally, NPPB prevents the ET-1 induced changes in vessel wall and neurons in the brain stem. CONCLUSION: The results of this study add further insights to our armamentarium against cerebral vasospasm.

Melatonin Modulates NMDA-Receptor 2B/Calpain-1/ Caspase-12 Pathways in Rat Brain After Long Time Exposure to GSM Radiation.

AIM: To investigate the potential protective effects of melatonin on the chronic radiation emitted by third generation mobile phones on the brain. MATERIAL AND METHODS: A total of 24 male Wistar albino rats were divided into four equal groups. Throughout a 90-day experiment, no application was performed on the control group. The second group was exposed to 2100 MHz radiation for 30 minutes. Subcutaneous melatonin was injected into the third group. Subcutaneous melatonin injection was applied 40 minutes before radiation and then the fourth group was exposed to radiation for 30 minutes. At the end of the experiment, brain (cerebrum and cerebellum) tissues were taken from the subjects. Histochemical, immunohistochemical, ultrastructural and western blot analyses were applied. In addition to brain weight, Purkinje cells’ number, immunohistochemical H Score analyses and the results of the Western blot were examined statistically. RESULTS: With the application of radiation, neuronal edema, relatively-decreased numbers of neurons on hippocampal CA1 and CA3 regions, displacement of the Purkinje neurons and dark neurons findings were observed as a result of histochemical stainings. Radiation also activated the NMDA-receptor 2B/Calpain-1/Caspase-12 pathway, NMDA-receptor 2B and Calpain-1 with the findings being supported by western blot analyses. Pre-increased protein synthesis before apoptosis was identified by electron microscopy. CONCLUSION: Mobile phone radiation caused certain (ultra) structural changes on the brain and activated the NMDA-receptor 2B/ Calpain-1/Caspase-12 pathway; in addition, melatonin was found to be effective, but insufficient in demonstrating the protective effects.

Effects of chronic treatment with valproate and oxcarbazepine on ovarian folliculogenesis in rats.

PURPOSE: We aimed to define the morphologic effects of valproate (VPA) and oxcarbazepine (OXC) on ovarian folliculogenesis in rats. METHODS: Forty female wistar rats (21-24 days old and weighted between 46.4 and 55.3 g) were divided equally into 4 experimental groups, which were applied tap water (control group), 300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90 days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle according to daily vaginal smear were taken out and placed in a fixation solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were applied. RESULTS: The number of follicles decreased and that of corpora lutea increased significantly in OXC, VPA, and OXC+VPA treated groups compared with control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40 +/- 0.52 in control group, but it significantly increased to 3.50 +/- 0.53, 3.50 +/- 0.53, and 4.90 +/- 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The increase in the number of TUNEL positive granulosa cells was also significant for OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGF beta 1 and IGF1 staining and increased for P53 staining in all drug groups compared with control group (p < 0.001). Intensity of P53 labeling increased, while intensity of TGF beta 1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group (p < 0.001). CONCLUSION: Long-term treatment with VPA or OXC from prepuberty to adulthood causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.

Impact of high levels of progesterone on alpha(1)-integrin distribution in the endometrium of patients with unexplained infertility.

Irregular or low expression of integrins, which are cell adhesion molecules, may be associated with infertility. We conducted a prospective controlled study evaluating the effects of supraphysiological levels of estrogen and progesterone created by human menopausal gonadotropins (HMG) and progesterone support on alpha(1)-integrin immunolocalisation in the endometrium. Three groups were enrolled in the study. The first group of patients (group 1) had unexplained infertility and had been treated with HMG and progesterone (n=27). The second group of patients (group 2) was an untreated fertile group (n=24). The third group (group 3) consisted of patients who had unexplained infertility and had received no treatment (n=11). Endometrial biopsy specimens were taken from individuals from each group during the ovulation induction period. alpha(1)-integrin immunohistochemistry was performed. Serum estradiol and progesterone levels were also measured in parallel with histological dating of endometrial biopsies. Group 1 showed no statistical difference from group 2 in alpha(1)-integrin or histological dating. Group 3 showed less alpha(1)-integrin in the glandular epithelium in the secretory phase. We observed that alpha(1)-integrin was specific to the secretory phase. Its localization was denser in group 2 when compared with group 3, which supports the conclusion that alpha(1)-integrin may be a useful marker for luteal phase quality. Moreover, the supraphysiological estrogen and progesterone levels created by HMG and progesterone support may affect the alpha(1)-integrin in the endometrium in the secretory phase in the case of unexplained infertile patients.

Ultrastructural damage in lung tissues in rats treated with doxorubicin and paclitaxel.

INTRODUCTION: The aim of this study was to determine the ultrastructural effects of doxorubicin (Adriblastina; Pharmacia and Upjohn, Milan, Italy), paclitaxel (Taxol; BMS, Princeton, NJ), Cremophor EL (a diluent of paclitaxel) and doxorubicin/paclitaxel combinations on normal lung tissues. METHODS: In the experimental protocol, 50 Wistar albino rats were used, divided into five different groups: the control group (n=10), the doxorubicin group (1 mg/kg) (n=10), the paclitaxel group (2 mg/kg) (n=10), the Cremophor EL group (150 mg/kg) (n=10) and the paclitaxel/doxorubicin group (2 mg/kg+ 1 mg/kg) (n=10). The drugs were administered weekly to rats via intraperitoneal injections for 14 weeks. After 3 weeks of observation, the rats were killed with thiopental sodium (30 mg/kg) and their left median lung tissues were removed and examined with a Carl Zeiss EM 900 transmission electron microscope. RESULTS: Our experiments showed doxorubicin to cause an increase in collagen fibre content of the alveolar wall, and paclitaxel to cause degenerations in cellular organelles. In the group in which the two agents were administered together, both effects were observed, although the effects of paclitaxel were seen to be dominant. Ultrastructural appearance was similar in the Cremophor EL group compared to the control group. CONCLUSION: It was detected that doxorubicin and paclitaxel caused ultrastructural degenerations in normal lung tissues and Cremophor EL seemed to be unaccountable for these degenerations.

Ultrastructure of the thymus in diabetes mellitus and starvation.

INTRODUCTION: The purpose of this study was to investigate the ultrastructural change of the thymus under stress conditions created by diabetes accompanied by fasting, and also the effects of insulin therapy. METHODS: Forty-eight Sprague-Dawley type rats were used in this experiment. Type 1 diabetes symptoms were induced in 24 of the rats by the application of a single dose of intravenous streptozotocin in sodium citrate buffer through the tail vein. A single dose of sodium citrate buffer was given to rats to create a control group. Following the infusions, rats were divided into control, control and fasting, diabetes, diabetes and fasting, and insulin treatment groups. At the end of the experiment tissues from the thymus of the rats were extracted and examined using electron microscopy. RESULTS: Severe degeneration was observed in the prolonged fasting (stress) and diabetes groups without insulin treatment. Insulin treatment was found to mostly reverse this degeneration. CONCLUSION: This study demonstrates that the thymus was affected ultrastructurally by diabetes and concomitant fasting, and insulin treatment can reverse these changes.

Dose-dependent ultrastructural changes in rat cornea after oral methylphenidate administration.

OBJECTIVE: To investigate dose-dependent ultrastructural changes in rat cornea after oral methylphenidate Ritalin administration. METHODS: This study was conducted in the Department of Anatomy, Gazi University Faculty of Medicine, Ankara, Turkey between March and May 2005, with a total of 27 female prepubertal Wistar albino rats, divided into 3 different dose groups 5mg/kg, 10 mg/kg, 20 mg/kg, and their control groups. They were treated orally with methylphenidate, and eye tissue was removed to process for electron microscopic studies. RESULTS: We observed that all cells, and prominently basal cells of the corneal epithelium show dose-dependent degenerative changes such as apoptotic bodies, chromatin condensation, and ondulation in their nuclei and crystolysis of the mitochondrion. In the stroma, the most evident finding was the increase of the collagen fiber. In addition to dose-dependent changes related to the apoptotic process, which is chromatin condensation in their nuclei, electron dense material accumulation, and pericellular edema in the cytoplasm were also seen. In the endothelial cell lines, disruption of the junctional complexes, vacuolization in the cell cytoplasms, and crystolysis of the mitochondrion's with rough endoplasmic reticulum cisternae activity were observed. CONCLUSION: Ritalin is inducing an evident degeneration, especially in epithelium cells with increasing doses. Ultrastructural cell organelle composition degeneration with stromal fibrosis has a negative effect on cornea dehydration. In light of these findings, we believe that the Ritalin treatment doses need to be kept to a minimum to maintain healthy cornea ultrastructure and related physiology.

Effects of taurine in cellular responses to oxidative stress in young and middle-aged rat liver.

Aging is related with an increased cellular level of lipid peroxides and reactive oxygen species (ROS). The useful effects of taurine as an antioxidant in biological systems have been attributed to its capability to stabilize biomembranes, to scavenge ROS, and to decrease the peroxidation of unsaturated membrane lipids. The aim of the present study was to investigate the effects of taurine on malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), thioredoxin reductase (TR), and endothelial nitric oxide synthase (eNOS) in young and middle-aged rat liver. There was not a significant difference in liver MDA levels between the control groups of young and middle-aged rats (P > 0.05). However, liver GSH levels, and GPx and TR activities between the control groups of young and middle-aged rats were significantly different (P < 0.05). Liver MDA level was significantly lower in the taurine group of middle-aged rats (P < 0.05). Liver GSH levels, and GPx and TR activities were significantly increased in the taurine group of middle-aged rats when compared to the control group (P < 0.05). Liver MDA level was significantly lower in the taurine group of young rats than the ones in the control group (P < 0.05). Liver TR activity was significantly increased in the taurine group of young rats when compared to the control group (P < 0.05). Liver GPx activity was not statistically different between the taurine and the control groups in young rats (P > 0.05). Liver GSH levels were not different between the young taurine and the control groups (P > 0.05). Immunohistochemical studies exhibited no change in eNOS activity after taurine injection in young rats. However, in middle-aged rats, taurine lowered the eNOS reactivity to the same level found in young rats. These results suggested that exogenous taurine might play a role in aging by means of its reducing effects on free radical levels in parallel to an increase in the antioxidant capacity.

Effects of leptin on stress-induced changes of caspases in rat gastric mucosa.

BACKGROUND: In this study, we investigated the effect of leptin on caspase-3, caspase-8, and caspase-9 immunoreactivity and lipid peroxidation in the stomachs of rats exposed to cold-restraint stress. METHODS: Thirty-two male Wistar Albino rats were used. Rats pretreated with leptin (10 microg/kg per day for 7 days) were restrained in a wire cage for 4 h at 4 degrees C. Spectrophotometric techniques were used for detection of malondialdehyde (MDA) and glutathione (GSH) levels, and immunoreactivity of caspases was investigated by immunohistochemistry. RESULTS: While the stomach MDA level of the cold-restraint stress group was increased significantly, the level of GSH was decreased when compared with the control group. Caspase-9 and caspase-3 immunoreactivities of the stress group were not changed, while caspase-8 immunoreactivity was decreased. Leptin administration prevented the increase in the MDA level and the decrease in the GSH content of the gastric mucosa in animals subjected to stress. Leptin administration produced no significant change in caspase-8 immunoreactivity but caused a decrease in caspase-3 immunoreactivity. CONCLUSIONS: Cold-restraint stress decreases the antioxidant capacity of stomach tissue while activating oxidants, and induces apoptosis by an increase in caspase immunoreactivity. The presence of leptin reverses these mechanisms and suppresses the apoptosis.