Firdevs Gürer

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 Parkinsons 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.

Ovarian, uterine and brain mast cells in female rats: Cyclic changes and contribution to tissue histamine

Using histochemical techniques, we determined mast cell content in ovarian, uterine and brain tissues throughout the estrus cycle of the rat. In one series of experiments, 26 cycling female rats were used for the measurement of follicle stimulating hormone (FSH) in plasma and evaluation of mast cells in the tissues. In a second series, cycling female rats were used for the determination of tissue histamine. The number, degranulation pattern and staining characteristics of mast cells changed synchronously in rat ovarian, uterine and brain tissues during the estrus cycle. A great majority of mast cells in tissues were stained by Alcian blue at proestrus and metestrus. Safranin-stained mast cells were abundant in all tissues during estrus and diestrus. Alcian blue-stained mast cells contribute to the change of tissues histamine level. In ovarian tissue, histamine level increased significantly at proestrus and metestrus. The lowest ovarian histamine level was determined at estrus, in which virtually all mast cells were stained by safranin only. Mast cells in ovarian, uterine and brain tissues seem to change their histamine content throughout the estrus cycle. Mast cells are absent from the thalamus during proestrus and are present in the hypothalamus only during the estrus phase. Plasma FSH concentrations (mlU ml-1) did not significantly change throughout the estrus cycle (proestrus: 0.81 +/- 0.11, estrus: 0.69 +/- 0.07, metestrus: 0.82 +/- 0.13, diestrus: 0.67 +/- 0.19).

The effect of vasoactive intestinal peptide (VIP) on mast cell invasion/degranulation in testicular interstitium of immobilized + cold stressed and β-endorphin-treated rats

The effect of VIP on mast cell invasion/degranulation in testicular interstitium of stressed (immobilization and cold) and beta-endorphin-treated rats were investigated. Fifty-three Wistar male rats were used in four series of experiments. Initially, the effect of immobilization and cold stress on mast cell invasion and degranulation in testicular interstitium was examined in three age group of rats: 15 (n = 6), 30 (n = 6), and 45 (n = 7) days of age. Five animals per age group were used as controls. Because the most obvious effect of the stress on mast cell invasion/degranulation in testicular interstitium was observed in 45-day-old rats, the action of VIP in stressed and beta-endorphin-treated rats was only investigated at this age group. Mast cells and Leydig cells were evaluated by using histochemical and light microscopic protocols. Stress caused mast cell accumulation and degranulation in the testicular interstitium. Stress decreased heparin synthesis and possibly increased histamine content of mast cells. The effect of beta-endorphin was not as high as seen with stress. In some areas of testicular interstitium of stressed rats, there were aplasic and/or inactive Leydig cells. VIP inhibited proliferation and degranulation of mast cells, increased heparin content of the cells, and protected Leydig cells. By way of mast cell accumulation and degranulation in the testicular interstitium, exposure to stress may lead to Leydig cell damage and infertility. VIP may be involved in the protection of normal testicular function under stress conditions.

Mast Cell Degranulation in Hemorrhagic Shock in Rats and the Effects of Vasoactive Intestinal Peptide, Aprotinin and H1 and H2-Receptor Blockers on Degranulation

Various stressful stimuli cause mast cell degranulation. Hemorrhagic shock is one such stressful stimulus which may cause mast cell degranulation and histamine release. Histamine may be involved in the pathophysiology of hemorrhage. It was reported that there are large amounts of histamine in the anterior and posterior lobes of the pituitary and the adjacent median eminence of the hypothalamus. Most of the histamine in the posterior pituitary is in mast cells. In addition, both vasoactive intestinal peptide (VIP) and histamine-containing neurons are available in the hypothalamus. It therefore seems reasonable to suppose that these three systems (i.e., mast cells, VIP-containing neurons, and histamine-containing neurons) may play an important role in the progression of hemorrhagic shock. 66 albino rats (200-250 g) of either sex were used. The presence of mast cells was examined by light microscopy. Hemorrhage caused mast cell degranulation in a correlation with the amount of blood loss. In all cases, the most intense degranulation was observed in the hypothalamus, especially the nucleus arcuatus, and in the subcutaneous tissue. The intensity of degranulation gradually decreased in the peripheral blood vessel, peritoneum and omentum, in this order. VIP prevented degranulation, but aprotinin and H1 and H2 receptor blockers did not.

The effect of vasoactive intestinal peptide (VIP) and naloxone combination on survival rates in rats exposed to severe hemorrhage

In this experiment, the effects of different doses of vasoactive intestinal peptide (VIP) and naloxone (NLX) combinations on survival rates were investigated in rats exposed to 40% hemorrhage. A combination of 25 ng.kg-1 VIP+5 mg.kg-1 NLX showed the best results on survival. The important prospect of this combination is to have the most potent inhibitory effect on mast cell degranulation. When this combination was given together with shed blood reperfusion and 7.5% NaCl, survival rate increased relative to the administration of shed blood alone and of 7.5% NaCl. These findings suggest that inhibition of mast cell degranulation has a beneficial effect on severe hemorrhage.

Effect of Vasoactive Intestinal Peptide and Naloxone Combination on Urinary N-Acetyl-β-D-Glucosaminidase Level and Kidney Histology of Rats Exposed to Severe Hemorrhage

Renal hypoperfusion which occurs in hemorrhagic shock creates an environment in which cellular injury and organ dysfunction can occur during the episode of shock as well as reoxygenation and reperfusion. At the same time, mast cell degranulation which is observed during hemorrhage may have an additional deleterious effect on the kidney. Twenty-two (Mus norvegicus albinos) rats (200-250 g) of either sex were used. The animals were divided into three groups. Group 1, the control group, was exposed to a 40% hemorrhage. Group 2 was exposed to 40% hemorrhage and then shed blood reperfused. Group 3 was exposed to 40% hemorrhage, and in addition to shed blood reperfusion 25 ng kg-1 vasoactive intestinal peptide (VIP) + 5 mg kg-1 naloxone (NLX) were given. At the end of the experiment the kidneys were evaluated either histologically or by measurement of the urinary N-acetyl-beta-D-glucosaminidase (NAG) activity. Shed blood reperfusion caused continuation of ischemic tissue damage and elevation of urinary NAG activity. Addition of VIP and NLX to the blood reperfusion caused a decrease in urinary NAG excretion, and the histology of renal tissue was almost normal.

Effect of nitric oxide inhibition on rat liver ischemia reperfusion injury

Objective: to determine the role of nitric oxide (NO) in rat liver ischemia reperfusion we examined the effects of competitive NO synthesis inhibitor L-nitro-arginine-methyl-ester (L-NAME) and NO precursor L-arginin. Methods: 46 Sprague-Dawley rats were divided into five groups. Group 1, sham operated; group 2, 30-min ischemia administered; group 3, 60-min reperfusion administered after ischemia; group 4, 50 mg/kg L-NAME was given i.v. immediately before reperfusion; group 5, 50 mg/kg L-NAME+250 mg/kg L-arginin was given i.v. immediately before reperfusion. At the end of the experiment, liver was removed and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were measured, transaminases SGOT and SGPT were measured in sera. Liver was also evaluated histopathologically. Results: transaminase levels were the highest in ischemia reperfusion group. Transaminases in this group were high compared with sham, ischemia, L-NAME and L-arginin groups (***P<0.001, ***P<0.001, *P<0.05, *P<0.05, respectively). SOD activity was 29.8+4 U/mg protein in L-arginin group. This level was the lowest level in all groups. SOD activity in L-arginin group was lower than that of sham and ischemia reperfusion groups (**P<0.01, *P<0.05, respectively). There were no significant differences in catalase activity and MDA levels among groups. Tissue damage was significant in ischemia and ischemia reperfusion groups. Tissue damages in these groups were greater than that of sham group (***P<0.001). In L-NAME treated group, tissue damage was similar to sham group, and significantly less than ischemia reperfusion group and L-arginin group (**P<0.01). Conclusion: even though there was significant tissue damage, we have not observed oxidative stress in the length of ischemia reperfusion period that we have performed. Mechanism of this damage seems to be independent from lipid peroxidation. NO supplementation decreased SOD, but did not cause further tissue damage. NO may dispose O(2)(-) by formation of peroxynitrite. L-NAME did not change lipid peroxidation, but clearly reduced reperfusion injury.

Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas.

AIM To study the effect of vasoactive intestinal peptide (VIP) on wound healing in experimental alkali burns of the cornea. METHODS Twenty-seven albino rabbits, weighing 3.2±0.75 kg were used. Alkali burns were induced on corneas by applying 10 mm Whatman paper No:50 soaked in 1 mol/L NaOH. They have further classified into 5 groups as follows: 1) control group given no treatment (n=5); 2) VIP given subconjunctivally (n=6); 3) VIP injected into anterior chamber (n=6); 4) NaCl 0.9% given subconjunctivally (n=5); 5) NaCl 0.9% given into the anterior chamber (n=5). All treatment protocols except control group were followed by topical eye drops composed of VIP at two hourly intervals for one week from 8 a.m. to 6 p.m. RESULTS VIP treated groups of rabbits with alkali burns were found to have better wound healing findings histo-pathologically when compared to those of control group who have received no treatment on day 30. No differences were observed between groups in respect to degree of polymorphonuclear leukocytes (PMNL) infiltration and degree of loss of amorphous substrate on day 15. However, PMNL infiltration and degree of loss of amorphous substrate were lower in Groups 2 and 3 when compared to that of control group on day 30 (P<0.05). CONCLUSION We have shown that VIP has positive effects on alkali induced corneal burns. VIP may inhibit PMNL migration to cornea through an immunomodulatory effect. Inhibition of PMNL migration might reduce the release of collagenases and this might prevent the extracellular amorphous substance loss.

Efficacy of Prophylactic and Early Fluconazole Treatment on Systemic Candidiasis in Experimentally Neutropenic Rabbits

The efficacy of prophylactic and early fluconazole treatment on experimental systemic candidiasis was investigated in neuropenic rabbits. Fifteen rabbits were used and divided into three groups: fluconazole was started 24 h before the inoculation of Candida albicans in the first group, and 24 h after the inoculation in the second group. The third group was the control group without antifungal therapy. Prophylactic and early fluconazole treatment for 7 days after C. albicans inoculation did not reduce the mortality and tissue culture positivity in the rabbits significantly. Four of the five rabbits survived 7 days both in the prophylactic and early treatment groups. However, only one rabbit survived for 7 days in the control group. In diagnostic procedures, histopathological examination and evaluation with periodic acid-Schiff stain was found to be the most sensitive. In this study, prophylactic and early fluconazole treatment were found to be insufficient for treatment of systemic candidiasis in neutropenic rabbits.