Hippocampal neural cell loss in high-fat diet-induced obese rats-exploring the protein networks, ultrastructure, biochemical and bioinformatical markers.

OBJECTIVE: Obesity, which has become one of the main health problems, results from irregular and unhealthy nutrition. In particular, an increase in the intake of high-fat foods leads to obesity and associated disorders. It is noteworthy to specify that obese individuals have memory problems. This study aims to examine the effects of high-fat diet on hippocampus, with stereological, histopathological methods and STRING bioinformatic tool. METHODS: Female Adult Sprague Dawley rats (n = 20) were equally divided into control (CONT) and high-fat diet (HFD) groups. The control group was given standard rat pellet feed, while the high-fat diet group was fed with a 40 % fat content for 2 months. Following the feeding program, rats were sacrificed. The collected blood samples were analyzed biochemically to determine the level of oxidative stress while performing a stereological and histopathological examination of the brain tissues. Functional protein-protein networks for BDNF, C-Fos, CAT, LPO, SOD and MPO by gene ontology (GO) enrichment analysis were evaluated. FINDINGS: The number of neurons decreased in the HFD group compared to the CONT group. Damage to the histological structure of the hippocampus region; such as degenerate neurons, damaged mitochondria and extended cisterns of the endoplasmic reticulum was observed. Although C-Fos level and oxidative stress parameters increased in HFD group, BDNF level decreased. While BDNF and C-Fos were observed in pathways related to neuron death, oxidative stress and memory, BDNF was pronounced in the mitochondria, and C-Fos in the endoplasmic reticulum. DISCUSSION: This study shows that changes in both BDNF and C-Fos levels in obesity due to high-fat diet increase oxidative stress and cause neuron damage in the hippocampus.

Mirtazapine may show anti-hyperglycemic effect by decreasing GLUT2 through leptin and galanin expressions in the liver of type 1 diabetic rats.

OBJECTIVES: The aim of this study was to explore the molecular mechanism of mirtazapine with respect to energy metabolism in Streptozotocin-induced diabetic liver of rats by immunohistochemistry and Western blot. MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were assigned into 3 groups including control, type 1 diabetes mellitus (T1DM) group (55 mg/kg Streptozocin, IP) and T1DM+mirtazapine (20 mg/kg,PO) group. At the end of the experiment, blood glucose levels were measured and liver tissues were stained by Periodic acid-Schiff. Moreover, leptin and glucose transporter 2 (GLUT2) proteins were analyzed by western blot and immunohistochemistry; however, galanin were analyzed only by immunohistochemistry. RESULTS: At the end of the study, in diabetes group, blood glucose level, GLUT2 and galanin expressions increased, while leptin expression decreased when compared to control group. Mirtazapine treatment restored the decreased leptin expression, and the increased blood glucose level and galanine expression to the level of the control group. It also decreased the GLUT2 expression even below the control group. CONCLUSION: We concluded that mirtazapine may show its anti-hyperglycemic effect by decreasing GLUT2 through altering the leptin and galanin expression in the liver of type 1 diabetic rats. Mirtazapine can be used as an antidepressant for T1DM patients and as a drug to reduce blood glucose level in T1DM.

Beneficial effect of mirtazapine on diabetes-induced hyperalgesia: involvement of TRPV1 and ASIC1 channels in the spinal cord and dorsal root ganglion.

OBJECTIVES: Neuropathic pain reduces the life qualities of patients with Diabetes mellitus. Clinical guidelines recommend relief in diabetic neuropathic pain through the use of some antidepressants, anticonvulsants, opioids as well as capsaicin cream or lidocaine patches. However, since the majority of patients do not or partially respond to current treatments, there is a growing necessity for new drugs increasing the pain relief in patients with diabetes. Therefore, based on the therapeutic potential of antidepressants on neuropathic pain, we investigated the promising antihyperalgesic effect of mirtazapine (MRT) in painful diabetic neuropathy. METHODS: Experimental diabetes was induced in rats by single intraperitoneal injection of 55 mg/kg dose of streptozocin (STZ). After 4 weeks of injection of STZ, MRT was administrated for 14 days at 40 mg/kg dose. Randall-Selitto and Hargreaves tests were applied for paw-withdrawal threshold and paw-withdrawal latency measurement. TRPV1 and ASIC1 expressions measured by Western blot in dorsal root ganglion and spinal cord. RESULTS: Administration of MRT significantly improved both of the decreased paw-withdrawal threshold and shortened the paw-withdrawal latency of diabetic rats, respectively. Besides, increased levels of TRPV1 and ASIC1 channels in dorsal root ganglion and spinal cord of diabetic rats, evaluated by Western blot method, were decreased following the MRT treatment. DISCUSSION: These data show, for the first time, that MRT has beneficial effects against diabetes-induced hyperalgesia, and that suppressive effect of this drug on TRPV1 and ASIC1 levels, which are increased in diabetic rats, may be some of the pharmacological mechanisms underlying the exhibited antihyperalgesic effect of MRT.

Mirtazapine suppresses sterile inflammation through NLRP3-inflammasome in diabetic rat kidney.

AIM: The aim of this study was to investigate the effects of mirtazapine, which is anti-oxidative and antidepressant agent, on the kidney damage caused by diabetes mellitus. MATERIALS AND METHODS: The rats were randomly divided into three groups (n = 7 animals in each group). The group I rats served as control and they received 0.1 mol/L of citric acid buffer (pH = 4.5) as vehicle. The rats in the group II (DM group) and III (DM + Mirtazapine-treated group) were treated intraperitoneally with a single dose of 55 mg/kg streptozotocin dissolved in 0.1 mol/L of citric acid buffer. Group III rats were also received 20 mg/kg/day of mirtazapine for 2 weeks. At the end of the experiment, the rats were sacrificed. Then, the kidneys were excised and prepared for microscopical examination. caspase-1 and NLRP3 proteins were examined using immunohistochemistry and western blotting. The TUNEL assay for apoptosis and ELISA assay for IL-1ß were performed. RESULTS: Histological examination showed that mirtazapine administration has an ameliorative effect on DM-induced kidney damage. Immunohistochemical and western blot analyses showed that NLRP3 and caspase-1 expressions were increased in the DM group according to the control group and the mirtazapine administration decreased these expressions. The intraglomerular and tubular TUNEL-positive cells were numerous in the DM group compared to the mirtazapine-treated group. The level of IL-1ß was highest in the DM group, and decreased significantly in the mirtazapine-treated group. CONCLUSION: In this study, 20 mg/kg/day mirtazapine administration for 2 weeks reduced NLRP3 and caspase-1 expressions and IL-1ß level in the diabetic rat kidneys. These results suggesting that mirtazapine may be useful in the treatment of DM and other metabolic diseases. Advanced molecular studies are needed to elucidate the exact effects of mirtazapine on NLRP3 inflammasome.

Comparison of the Effects and Mechanism of the Curcumin with Different Drugs in Experimental Vasospasm After Subarachnoid Hemorrhage.

AIM: Cerebral vasospasm following subarachnoid hemorrhage (SAH) is the most important complication that effects the mortality and morbidity of patients with intracranial aneurysm. Today, the mechanisms of vasospasm are not understood in spite of experimental and clinical researches. The aim of our study was to investigate the effects of curcumin on vasospasm following SAH. MATERIAL AND METHODS: In this study, 64 rats (200-250 g weight) were divided into 7 groups. Group 1: having no treatment after SAH; Group 2: treatment with nimodipine after SAH; Group 3: treatment with nicorandil after SAH; Group 4: treatment with sildenafil citrate after SAH; Group 5: treatment with 150 mg/kg curcumin after SAH; Group 6: treatment with 300 mg/kg curcumin after SAH, Group 7: treatment with 600 mg/kg curcumin after SAH. The experimental SAH was induced by injection of autologous blood into the cisterna magna. After medical treatment, in the first hour, blood was taken for quantified the levels of TNF-α, IL-1ß and IL-6. Then, cerebrum and cerebellum were removed for analysis. Basilar artery luminal diameter was measured and apoptotic cell count was performed with tissue samples. RESULTS: Histopathological findings showed that, in sufficient dose, curcumin dilated the basilar artery beside anti-oxidant effect. CONCLUSION: Curcumin can be used for the treatment of vasospasm as a new medical drug.

Neuroprotective Effect of Genistein in Peripheral Nerve Injury.

AIM: To investigate the effects of genistein in a rat model of sciatic nerve crush injury and complete sciatic nerve transection. The effects of genistein were compared with those of gabapentin, which is widely used in clinical practice for peripheral nerve injury. MATERIAL AND METHODS: Forty-eight rats were randomly divided into six groups (8 rats in each group): group 1 (sham); group 2, sciatic nerve crush injury (control); group 3, sciatic nerve crush injury+genistein 20 mg/kg; group 4, sciatic nerve crush injury+gabapentin 90 mg/kg; group 5, sciatic nerve transection+genistein 20 mg/kg; group 6, sciatic nerve transection+gabapentin 90 mg/kg. The effects of genistein and gabapentin were assessed with immunohistochemical staining for growth associated protein-43 (GAP-43) and myelin basic protein (MBP). Interleukin-1ß and tumor necrosis factor α levels in the injured nerve specimens were assessed as a measure of inflammatory response; walking track analysis and sciatic function index for neurological recovery and the paw mechanical withdrawal threshold were examined for neuropathic pain. RESULTS: On histopathological examination, genistein use was associated with a greater immunoreactivity for GAP-43 and MBP compared with that associated with gabapentin. Genistein and gabapentin had similar effects on anti-inflammatory activity, functional recovery, and neuropathic pain. CONCLUSION: Genistein and gabapentin exhibit positive effects on histopathology, inflammation, and clinical findings of peripheral nerve injury. When the systemic side effects of gabapentin are considered, genistein (a basic soy isoflavone that has no side effects) can be used as an alternative to medical treatment in peripheral nerve injury.

Resveratrol reduces IL-6 and VEGF secretion from co-cultured A549 lung cancer cells and adipose-derived mesenchymal stem cells.

Stem cell therapies are important treatment methodologies used in many areas of experimental or clinical medicine. In recent studies of cancer models, Mesenchymal stem cells (MSCs) suppressed the growth of cancer cells. However, also in some studies, stem cell treatments have been shown to induce cancer formation, increase tumor volume, induce the formation of new vessels, and lead to cancer invasion. The presence of MSC-secreted cytokines and their effects on cancer cells limits the reliability of MSC-based treatments. Resveratrol (trans-3,5,4'-trihydroxystilbene), an antioxidant found in red wine, has been shown to have therapeutic effects against several cancers. The aim of this study was to co-culture MSCs with A549 cancer cells to suppress the release of cancer-promoting cytokines from MSCs and to increase the applicability and reliability of stem cell therapies with resveratrol. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red cell viability assays were used to find safety dose of resveratrol. The MSCs secreted the cytokines IL-6 and VEGF, and the effect of resveratrol on these cytokines was analyzed by ELISA and western blot analysis of conditioned medium. One µM of resveratrol was found to be the safety dose for the A549 cancer cells and MSCs. We observed the highest release of IL-6 and VEGF from the co-cultured A549 cells and MSCs, and resveratrol was found to significantly decrease the release of these cytokines. Our study suggests that resveratrol exerts a positive effect on the release of cytokines. The safety dose of resveratrol can be administered together with stem cells during stem cell treatment.

Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration.

Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice.

This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman's capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injection for 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects.

Antioxidant effects of melatonin and coenzyme Q10 on oxidative damage caused by single-dose ochratoxin A in rat kidney.

In the study, the effects of relatively high single-dose of Ochratoxin A (OTA) and the antioxidant effects of Melatonin (Mel) and Coenzyme Q10 (CoQ10) on OTA-induced oxidative damages in rats were investigated. A total of 28 male Sprague-Dawley rats were divided into four groups of 7 rats each: Control, OTA, Mel+OTA and CoQ10+OTA groups. Malondialdehyde (MDA) levels in the plasma and glutathione (GSH) levels in whole blood were measured; kidneys (for histological inspection and for apoptosis detection by TUNEL method) and bone marrow samples (for chromosome aberration and mitotic index) were taken. The rats in the OTA group showed limited degeneration of tubular cells. In some tubules karyomegaly, desquamated cells and vacuolization were observed by light microscopy. Mel and CoQ10 treatment significantly reduced the severity of the lesions. MDA levels of the OTA group were significantly higher than the control, OTA+Mel and OTA+CoQ10 groups, while GSH levels were significantly lower than the control, OTA+Mel and OTA+CoQ10 groups. Higher incidences of apoptotic bodies were observed in the kidneys of the OTA group although OTA administration did not significantly change the incidence of apoptotic bodies when compared to the control and antioxidant administrated groups. Although the percentage of the mitotic index was lowest in the OTA group, no statistical difference was found among the groups. Additionally, OTA had no numerical and structural significant effects on chromosomes. It was observed that single-dose OTA administration caused oxidative damages in rat kidney and Mel or CoQ10 treatment appeared to ameliorate the OTA-induced tissue injuries.

Latanoprost-induced changes in the iris and trabeculum: an electron-microscopic morphological study.

PURPOSE: The purpose was to analyze the histological aspects of irises and trabeculums by transmission electron microscopy (TEM) in patients who had or had not received latanoprost therapy. MATERIALS AND METHODS: Seven patients with pseudoexfoliation glaucoma were enrolled in the study. Four of them had been using latanoprost monotheraphy for 2 months. Iris samples were obtained by peripheral iridectomy. Trabeculum samples were obtained during the trabeculectomy without use of antimetabolites. The specimens were further processed for transmission electron microscopy. RESULTS: There was extracellular pigmentation in the iris stroma in four patients treated with latanoprost, whereas in the control group there was no free melanin in the stroma. Intracellular pigment in fibroblasts, melanocytes, or both was present in all samples in the study group. More pigment accumulation was found in the trabecular endothelial cells of the patients who had received latanoprost therapy. CONCLUSION: Latanoprost therapy causes pigment accumulation in the iris and trabeculum of patients in short-term therapy.

Protective effects of zinc on testes of cadmium-treated rats.

In this microscopic study, the toxic effects of cadmium (Cd) and the protective role of a zinc (Zn) co-treatment were investigated in the testes of the rats treated with Cd. At the dose and duration used, Cd severely damaged the seminiferous tubules and caused the degeneration and disintegration of spermatogenic cells. Leydig cells were also lost after Cd treatment. The present study showed that zinc co-treatment protected testes against toxic effects of cadmium.

Dexanabinol prevents development of vasospasm in the rat femoral artery model.

We postulated that a multi-potential agent such as dexanabinol may prevent the development of vasospasm after subarachnoid hemorrhage. We tested the effect of dexanabinol (10 mg/kg) on established vasospasm in a rat femoral artery model. Dexanabinol was given as single or repeated doses. On the 7th day after blood application, vessels were prepared for transmission electron microscopy studies, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining, and studying vessel morphology including luminal area and wall thickness. Application of blood to femoral artery caused a significant narrowing of luminal area (p<0.001) and a marked increase of radial wall thickness (p<0.001) when compared to controls. Similar to its single injection, repeated doses of dexanabinol markedly widened luminal area (p<0.001) near to control values (p>0.05) and decreased radial wall thickness significantly compared to hemorrhage (p<0.05) and vehicle-treated groups (for single p<0.05 and repetitive injections p<0.01). Both single and multiple dexanabinol injections also lowered apoptotic index (p<0.001). In conclusion, dexanabinol seems to prevent established vasospasm and endothelial cell apoptosis.

Experimental study on axial pedicled composite flap prefabrication with high density porous polyethylene implants: medporocutaneous flap.

Composite flaps including soft tissues with bone or cartilage are widely used in reconstruction of three-dimensional defects, but have some disadvantages. Flap prefabrication with alloplastic implants is an alternative procedure. Axial pattern vascularised high density porous polyethylene (HDPP) implants are capable of sustaining skin grafts. The purpose of this study was to examine the vascularisation pattern of the skin island in a composite flap prefabrication model prepared with vascularised HDPP implants. Forty male Wistar rats divided into four groups were used. A 9.5 x 6 x 2 mm HDPP block was centered on the dissected saphenous pedicle and anchored under the abdominal skin in the experimental group I (n=10). In experimental group II (n=10) saphenous artery and vein were put between the skin and the implant. Thus, the structures were laid as skin, HDPP block, pedicle in experimental group I and skin, pedicle, HDPP block in experimental group II. HDPP block-implanted and pedicle-implanted only groups served as control groups I and II, respectively. Eight weeks after prefabrication, skin islands 1.5 x 5 cm in size incorporated with implants were elevated based on saphenous vessels in the experimental groups and skin islands only based on the pedicle in control group II. Skin islands of the same dimensions were raised as grafts in control group I. Nylon sheets were put under the flaps and grafts to prevent vascularisation from the recipient bed. Flap viability was assessed by measuring the surface area on the 7th day. Total necrosis developed in composite grafts of control group I. Flap survival was higher in experimental group II and control group II (45% and 46.8%) than in group I (29.28%). Histologic studies demonstrated fibrovascular ingrowth into the HDPP implants, except in control group I, with significant inflammatory response and necrosis. Vascularisation of skin and implants from the pedicle was seen also microangiographically. In conclusion, a composite flap prefabrication model including vascularised HDPP implant, skin and vascular carrier was developed. This new flap was termed a 'medporocutaneous flap'.

A missense mutation in the M1S1 gene found in a turkish patient with gelatinous droplike corneal dystrophy.

PURPOSE: To report a missense mutation in the M1S1 gene found in a Turkish patient with gelatinous droplike corneal dystrophy (GDLD). METHODS: A Turkish patient with GDLD was examined. Keratoplasty was performed and a diagnosis of GDLD was made by histopathologic and electron microscopic studies. Genomic DNA was extracted from peripheral blood and the paraffin-embedded tissue of the corneal button. A 248-bp DNA fragment of the M1S1 gene was amplified, and sequencing reactions were analyzed. The results were compared with those of 30 healthy, nonrelated individuals. RESULTS: On light microscopic examination, sheets of amorphous amyloid deposits were observed in subepithelial regions and in the anterior and midcorneal stroma. Electron microscopy revealed dense collagen fibrils and entrapped filamentous amyloid fibrils in the corneal stroma. A substitution of T-->C at nucleotide 557 was found in the peripheral blood DNA sequence analysis, which resulted in an amino acid substitution of L-->P (L186P). Results were confirmed by direct DNA sequencing analysis of the paraffin-embedded corneal button. The patient with GDLD was homozygous for the mutation, resulting in amino acid substitution L186P. CONCLUSIONS: This is the first report, to our knowledge, of a homozygous mutation (L186P) in the M1S1 gene found in a Turkish patient. The clinical examination may be insufficient in sporadic cases, and histopathologic examination and molecular genetic analysis can accelerate and improve the accuracy of diagnosis in patients with GDLD.

Effects of intraarticular contrast media on synovial membrane and cartilage. An electron microscopic evaluation in rabbit knees.

OBJECTIVE: To evaluate the histological and ultrastructural alterations in rabbit knee joint cartilage and synovia induced by intraarticular injections of 2 water soluble contrast agents. METHODS: The study was conducted at the Department of Orthopedics and Traumatology, Medical Faculty, Osmangazi University, Eskisehir, Turkey in January 2002. To examine the effect of contrast agents on articular cartilage and synovial membrane, rabbit model was used. Specimens from 62 knee joints were examined by light microscopy and transmission electron microscopy one hour, one day, one week and 2 weeks after intraarticular administration of gadolinium-diethylenetriamine pentaacetic acid, iopromide or saline. RESULTS: In the knees injected with saline, light microscopic changes of the synovium consisted of edema only. Edema and hyperemia were seen in contrast agent injected knees. Ultrastructurally, numerous and large pinocytotic vesicles in A cells of the synovial membrane were seen in contrast agent injected groups. In the knees injected with saline the cartilage were ultrastructurally normal but contrast agent injected knees showed increased activation of chondrocytes with increase of dense glycogen accumulation, large lipid vacuoles and matrix material. There were very rare pycnotic cells in these samples. The rating scale has been used and the means of the total scores were determined for the groups. CONCLUSION: The effects of contrast agents reduced gradually on the cartilage and synovium in general but did not become completely normal in the observation period.

Interleukin-10 gene transfer: prevention of multiple organ injury in a murine cecal ligation and puncture model of sepsis.

INTRODUCTION: The aim of this study was to determine the effect of immunoregulatory cytokine interleukin-10 (IL-10) gene therapy on multiple organ injury (MOI) induced by a cecal ligation and puncture (CLP) model of sepsis in mice. METHODS: Male Balb/c mice subjected to CLP were treated with either an hIL-10-carrying vector or an empty control vector. We assessed the degree of lung, liver, and kidney tissue destruction biochemically by measuring myeloperoxidase (MPO) and malondialdehyde (MDA) activity. Histologic assessments were based on neutrophil infiltration in lung and liver tissue. IL-10 protein expression was examined immunohistochemically, and ultrastructural changes in the liver were studied by transmission electron microscopy. We analyzed the expression of tumor necrosis factor-alpha (TNFalpha) mRNA by reverse transcription polymerase chain reaction 3, 8, and 24 hours after CLP in all organs. RESULTS: Organ damage was significantly reduced by hIL-10 gene transfer, which was associated at the tissue level with reduced MPO activity in the liver, lung, and kidney and decreased leukocyte sequestration and MDA formation in the lung. The liver MDA was not significantly higher in the hIL-10 gene therapy group than in the controls and seemed not to be affected by hIL-10 gene transfer. The reduced portal tract neutrophilic infiltration and preserved ultrastructure of the hepatocytes also showed that tissue function was not impaired. The lung and kidney TNFalpha mRNA expression was suppressed markedly in the hIL-10 gene therapy group, but liver TNFalpha mRNA expression varied over time. CONCLUSIONS: These findings showed that IL-10 gene therapy significantly attenuated sepsis-induced MOI.

Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats.

AIM: To evaluate the protective/ameliorative effects of vitamin E (vit E) on ethane dimethane sulfonate (EDS)-induced testicular toxicity in rats. METHODS: The rats were assigned to eight groups, seven rats in each, and were injected intraperitoneally with vehicle, a single dose of ethane dimethane sulfonate (EDS) (75 mg/kg bodyweight), vit E (100 mg/kg bodyweight) or EDS + vit E for 3? days. Thereafter, the rats were weighed, anaesthetized with ether and killed by cervical dislocation. The left testis weights were recorded and the relative testis weights were calculated. The left testes were processed for routine paraffin embedding. Three right testes from each group were taken randomly and then processed for routine electron microscopy. Tissue sections were examined using light and electron microscopy, and were scored for histopathological changes. RESULTS: Vit E coadministration did not prevent the bodyweight loss on days 3 and 7. However, vit E administration prevented the EDS-induced testicular-weight loss in rats that received vit E for 3 days but not 7 days. The relative testis weight was higher on day 3 (instead of on day 7) than other groups. Nevertheless, the testis histology was not markedly protected by vit E in the EDS-treated rats. Detailed microscopic assessment showed few Leydig cells and abundant fibroblast-like cells indicating only some protection. CONCLUSION: Vit E cotreatment showed partial protective effects on the testicular weight and testicular histology in rats that received EDS.

Neuroprotective effects of L-carnitine and vitamin E alone or in combination against ischemia-reperfusion injury in rats.

BACKGROUND: Neurological injury because of transient cerebral ischemia is a potential complication of cardiovascular surgery. In this study, the neuroprotective effects of L-carnitine, vitamin E, and the combination of these agents on ischemia/reperfusion (I/R) injury were determined in a rat model of transient global cerebral I/R. METHODS: Rats were pretreated with L-carnitine (100 mg/kg, i.v.) and vitamin E (50 mg/kg, i. v.), alone or in combination and then subjected to cerebral I/R induced by a four-vessel-occlusion technique for a duration of 15 min followed by 15 min of reperfusion. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and glutathione (GSH) levels were measured in the cerebral tissues. Histopathological examinations were also carried out under light and electron microscopy. RESULTS: The results showed that I/R elevated MDA levels, which were accompanied by a reduction in SOD activities and GSH levels. Surviving neurons was markedly decreased in CA1 and CA3 subfield of hippocampus in I/R animals. L-carnitine, vitamin E, and their combination restored MDA levels and SOD activities, with a tendency to increase surviving neurons in CA1 and CA3 subfield. Combined treatment of L-carnitine and vitamin E had better GSH levels than individual treatment of these agents. CONCLUSIONS: The results suggest that L-carnitine has a potent neuroprotective effect against cerebral-I/R-induced injury in rat brain that is comparable to that of vitamin E. However, the combined use of L-carnitine and vitamin E does not further protect from neuronal injury, although it provides an increase in GSH levels.

Brain mast cells and therapeutic potential of vasoactive intestinal peptide in a Parkinson's disease model in rats: brain microdialysis, behavior, and microscopy.

In the present study, the effect of systemically administered vasoactive intestinal peptide (VIP) (25 ng/kg i.p.) was investigated on drug-induced rotational behavior, extra-cellular dopamine levels and histology of corpus striatum in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. After 15 days of 6-OHDA lesion, apomorphine-induced (0.05 mg/kg s.c.) rotational behavior of the animals significantly increased and extra-cellular dopamine levels of corpus striatum were significantly reduced. VIP reversed the rotational deficits but did not alter the decrease in striatal dopamine levels. On the other hand, histological data indicate that VIP significantly reduced neuronal death and demyelination. Electron microscopic appearance of mast cells showed ultra-structural variety between VIP-treated and 6-OHDA lesioned groups. VIP activates mast cells without any evidence of typical exocytosis, and possibly mast cells could participate in neuroprotection. Our results suggest that systemically administered VIP can attenuate the motor response changes, neuronal cell death, and myelin sheet loss characteristically associated with 12 microg 6-OHDA administration into the rat striatum. Brain mast cells seem to participate in neuronal protection. Possibly, protective cues could be produced by brain mast cells.