Deniz Erdogan

Antioxidant and triglyceride-lowering effects of vitamin E associated with the prevention of abnormalities in the reactivity and morphology of aorta from streptozotocin-diabetic rats

In this study, we evaluated the effects of vitamin E on the vascular reactivity and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma glucose, cholesterol, and triglyceride concentrations in rats were increased markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic rats compared with controls. The rings of thoracic aorta with or without endothelium were mounted in organ chambers for measurement of isometric tension and were contracted by a single dose (10-5 mol/L) and then cumulative doses of noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue (MB) or removal of the endothelium resulted in a similar degree of enhancement in NA-induced contraction of control rings. STZ-diabetes increased the fast and slow components of NA-induced contraction in all experiments. The maximal contractile response of aorta to NA was also augmented by STZ-diabetes, whereas the sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant increases in the maximum contractile response and sensitivity of aorta to KCl. STZ-diabetic rats showed a significant reduction in the percentage of endothelial response (PER). A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.

An investigation on skin wound healing in mice with a taurine-chitosan gel formulation.

Summary. The process of wound healing begins immediately following surface lesions or just after exposure to radiation, chemical agents or extreme temperatures.Taurine (2-aminoethane sulfonic acid), an amino acid containing sulfur, is found in almost all tissues in mammals, playing various important physio-logical roles in each organ. Taurine exhibits an antioxidant effect and is also known to have effects on cell proliferation, inflammation and collagenogenesis. Many antioxidants have been used to eliminate the negative effects of oxygen free radicals on wound healing.The objective of the present study was to examine the wound healing effect in mice of taurine-chitosan gel, which releases taurine slowly over a long time period. Fifty mM of taurine in 1.5% chitosan polymer (TAU-GEL) and 1.5% chitosan polymer (CHI-GEL) were applied to full thickness skin wounds of mice once a day for seven days. After seven days of treatment, lipid peroxide formation-malondialdehyde (MDA) and hydroxyproline (HPX) levels and the tensile strength of wound tissues were measured. All results were compared with those of the untreated control group (CONT). The structural alterations in the skin layers were also histologically investigated.It was found that locally administered TAU-GEL form significantly increased wound tensile strength by decreasing the MDA and increasing HPX levels. These results were supported by histological findings. All observations suggest that taurine gel may be effective in wound healing.

Effects of Taurine in Cellular Responses to Oxidative Stress in Young and Middle‐Aged Rat Liver

Abstract:  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.

Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations.

Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

Effect of EGF dosage forms on alkali burned corneal wound healing of mice

The local treatment effects of EGF forms on alkali burned mice corneal wounds were identified. The corneal wounds were induced by 0.5 M NaOH solution on the corneal surfaces of the mice. The local epidermal growth factor solutions (100 ng/ml) and gel form in 0.2 per cent w/w carbopol 940 (100 ng/ml) were dropped in 5 microliters aliquots into the eye twice a day. The corneal wounds were measured for 15 days at 7-day intervals and examined histologically at the end of 15th day of the experimental period. The results indicated that topical epidermal growth factor treatment in solution improved the healing of alkali burned corneal wounds when compared with epidermal growth factor delivered in a polymer system.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Rectal and vaginal administration of insulin–chitosan formulations: An experimental study in rabbits

Insulin is a polypeptide drug and it is degraded by gastrointestinal enzymes, therefore, it cannot be used via oral route readily. There are only parenteral forms available in the market. The aim of this study was to investigate the effect of rectal and vaginal administration of various insulin gel formulations on the blood glucose level as alternative routes in rabbits. Chitosan gel (CH-gel) was used as a carrier; the penetration enhancing effect of sodium taurocholate and dimethyl-β-cyclodextrin (DM-βCD) was also investigated. CH-gel provided longer insulin release. The maximum decreasing effect on blood glucose level was observed with insulin–CH-gel containing 5% DM-βCD. In conclusion, our results indicate that insulin may penetrate well through the rectal and vaginal mucosae from the CH-gel. DM-βCD was also found to be a useful agent to enhance the penetration of insulin through rectal and vaginal membranes.

Changes in Isoprenaline-Induced Endothelium-Dependent and -Independent Relaxations of Aorta in Long-Term STZ-Diabetic Rats: Reversal Effect of Dietary Vitamin E

1. The present study concerns in vitro isoprenaline (ISO)-induced relaxation of aortic rings of long-term streptozotocin (STZ)-diabetic and nondiabetic rats, both with and without dietary vitamin E supplementation. 2. Incubation with propranolol, NG-nitro-L-arginine methyl ester and methylene blue, as well as absence of endothelium, all negatively affect the ISO-induced relaxations. 3. Thiobarbituric acid reactivity levels used as an index of lipid peroxidation are elevated in the aorta by diabetes. Four months of STZ-diabetes results in a significant increase in the ISO-induced relaxations together with endothelial dysfunction in the rat aorta. Diabetes also causes the loss of vascular integrity. 4. Dietary vitamin E supplementation during the last 2 months of diabetes allows normalization of the levels of lipid peroxides. This vitamin also completely reverses the increased sensitivity (pD2 value) of the aorta to ISO, whereas the maximum ISO-induced relaxations are partially restored after the treatment in diabetic rats. 5. The results suggest that ISO-induced relaxation in the aorta partially depends on the intact endothelium and that the endothelium-dependent relaxant effect of ISO is mediated by endothelium-derived relaxing factor. Results also indicate that abnormal vascular reactivity and structure of the diabetic rat aorta may be related to the increased lipid peroxidation. In conclusion, vitamin E can protect the arterial wall from oxidative stress-induced injury associated with chronic STZ-diabetes and allows normalization of the response to ISO and the structure of the aorta in diabetic rats.

The effect of EGF application in gel form on histamine content of experimentally induced wound in mice

Summary.The factors participating to the wound healing are complex and still obscure. Among these factors, epidermal growth factor (EGF) and histamine by increasing reepithelization and reparation tissue strength via enhancing collagen deposition to the wound site have a beneficial effect. This study was performed to investigate the effect of EGF dosage forms on the histamine content of the experimentally induced wound and some wound healing criters in the mice.Histological investigation of reepithelization, wound tensile strength for healing and collagen maturation, and histamine levels were assessed in the present study. Thirty two mice were divided into control, and EGF treated groups. Controls included three subgroups; untreated (n=5), 0.9% NaCl applied (n=5), and gel applied (n=5). Experimental groups were treated with two forms of EGF; EGF, solution form in 0.9% NaCl (n=5) and the gel form in 0.2% w/w in carbopol 940 (n=7). The discrepancy between these forms were evaluated. This evaluation was done by the application of two forms of EGF for 15 days on experimentally induced wound healing.Gel form of EGF by sustained release from bioadhesive polymer is found to be more effective than the soluble form, on the healing of the wound, by acceleration of reepithelization and increment of wound tensile strength. The tensile strength of the wound indicates the rate of repair and collagen maturation. It has been observed that when physiological saline and carbopol 940 exposed to incision without EGF causes a significant increase in tissue histamine content.According to the results of the present investigation; the histamine content is found to be decreased by EGF gel dosage form treatment, therefore preventing abnormal collagen formation has a beneficial effect on wound healing.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.