Bilge Gönül

The effects of vitamin C supplementation on oxidative stress and antioxidant content in the brains of chronically exercised rats.

The purpose of this study was to ascertain whether vitamin C supplementation during chronic exercise training alters rat brain antioxidant content. Female Wistar albino rats were exercised on a treadmill for 30 min/day for 6.5 weeks and were administered daily intraperitoneal injections of vitamin C (20 mg/kg). After the training period, chronically exercised rats showed no significant changes in total brain thiobarbituric acid reactive substances (TBARS) levels. In contrast, rats supplemented with vitamin C during the training period showed significantly elevated brain TBARS levels. If such results were extrapolated to man, where vitamin supplementation is a common practice, this would indicate that vitamin C supplementation may not protect brain tissue against exercise-induced oxidative damage, in such circumstances, this water-soluble antioxidant behaves as a pro-oxidant. (Mol Cell Biochem xxx: 135–138, 2005)

Effects of epidermal growth factor dosage forms on dermal wound strength in mice

Abstract— The effect of topically administered epidermal growth factor (EGF) dosage forms was investigated on skin wound healing in mice. Two EGF dosage forms were prepared containing 100 ng mL−1 EGF. The solution dosage form was prepared in 0·9% w/v NaCl. A bioadhesive gel form was prepared in 0·2% Carbopol 940 polymer. The two dosage forms were applied on the skin incision wounds of mice at the rate of 5 μL twice a day for 7 and 15 days. The wound tear strength was tested for skin wound healing at the 7th and 15th days of treatment and compared with controls. The results indicate that the wound tear strength of mice were significantly higher at the 15th day of treatment in the gel‐treated group compared with the solution‐treated mice and controls (P < 0·001).

Differential effects of pharmacological doses of melatonin on malondialdehyde and glutathione levels in young and old rats.

Background: The free radical theory of aging suggests the oxygen-derived species as the causative agents and free radical scavengers as the defense systems in aging process. The exact role of the free radical scavenging effects of melatonin in aging remains to be clarified. Objective: In this experimental study, we investigated the age-related changes of malondialdehyde (MDA), a lipid peroxidation product, and glutathione (GSH) and the effects of exogenous melatonin. Methods: Plasma, liver, and lung MDA and GSH levels of 9- and 28-month-old rats were measured. Results: Plasma, lung, and liver MDA levels of old rats were significantly higher than those of the young ones (p = 0.024, p = 0.005, and p = 0.0007, respectively). However, while the lung GSH levels were found to be significantly decreased in the control group of old rats as compared with young ones (p = 0.005), the liver GSH levels were unchanged. Plasma MDA levels were found to be significantly lower in the melatonin group of old rats as compared with the control group (p = 0.020) but lung and liver MDA levels were not significantly different. There were no significant differences in the levels of measured parameters between both groups of young rats. Conclusion: Our results suggest that increased levels of lipid peroxidation products may have a role in aging, and exogenous melatonin may delay the aging process of tissues by means of its free radical scavenging effects.

Effects of epidermal growth factor microemulsion formulation on the healing of stress-induced gastric ulcers in rats.

The effects of intragastric (i.g.) administration of microemulsion formulation of epidermal growth factor (EGF) on the healing of acute gastric ulcers induced by cold-restraint stress in rats was studied and compared with intraperitoneal (i.p.) administration of solutions. In the microemulsion formulation (W/O), labrafil M 1944 CS was the oil phase. Arlacel 186 and Brij 35 were used as the surfactants. Absolute alcohol and distilled water were used as the co-surfactant and the aqueous phase, respectively. Acute gastric lesions were induced by cold-restraint stress for 4 h in the refrigerator (4.0+/-0.5 degrees C). EGF was administered at a dose of 6 microg/kg per day intraperitoneally and intraperitoneally for 7 days. Basal gastric acid secretion (microequiv. H+/30 min), ulcer score (mm(2)) and tissue mucus levels (microg/g tissue) were measured. Basal gastric secretion was significantly reduced after the administration of EGF microemulsion (ME+EGF) (P<0.05). There was no significant decrease in basal gastric acid secretion following i.p (IPEGF) and i.g (IG-EGF) of EGF administrations of solutions compared to their control groups (P>0.05). The results indicate that the highest reduction in the basal acid secretion was seen after the administration of a microemulsion of EGF formulation. The mean ulcer score was reduced by i.g treatment with the microemulsion dosage form of EGF in 7 days from 15.9+/-1.4 to 1.16+/-0.45 mm(2) and was almost completely healed in four of the animals. The results demonstrate that the ulcer score was significantly reduced in i.p. (IPEGF) solution (P<0.005), i.g (IG-EGF) solution (P<0.01) and i.g. microemulsion (ME+EGF) (P<0.01) treated groups compared to untreated group. In IG-EGF, ME+EGF treated groups, mucus levels increased significantly compared to their control groups(P<0.05 and P<0.01). In contrast, there was no significant change in the mucus levels following i.p. EGF administration (P>0.05).

Exogenous melatonin decreases age-induced lipid peroxidation in the brain.

Aging has been proposed as the major risk factor in most neurodegenerative disorders. Oxidative stress is one of the widely accepted hypotheses to explain the pathogenesis of the senescence-related disorders. In this research report we aimed to study the changes in the levels of malondialdehyde as an indicator of lipid peroxidation and glutathione (GSH) of anti-oxidant status during aging. We also studied the effects of exogenous melatonin (MLT) on lipid peroxidation and glutathione levels of different brain regions. A total of forty-seven, 4 (young), 14 (middle-aged) and 20 (aged) months-old male Wistar-albino rats were used in the study. The MDA levels were significantly correlated with increased age (p<0.001). The MDA levels were similar in the different regions of the brain in the younger rats. However, the MDA levels of the cerebellum were significantly lower than that of the frontal and occipital cortex of the aged animals. Exogenous melatonin treatment significantly decreased the MDA levels of all the examined brain regions in the aged groups (p<0.001). The GSH levels of all the examined brain regions were similar in young and middle-aged rats. The GSH levels were inversely correlated with the increasing age. While exogenous melatonin did not have any significant effect on the GSH levels of the different brain regions in the younger rats, it significantly increased in the aged group. Exogenous melatonin can prevent the increased production of age-related lipid peroxidation products and might have a potential role for retardation of age-related oxidative events.

Relationships between tensile strength, ascorbic acid, hydroxyproline, and zinc levels of rabbit full-thickness incision wound healing.

PurposeThis work was carried out to follow up the healing of full-thickness incision wounds opened on the back skin of rabbits in order to gain insight into the periodical correlation among such factors as ascorbic acid, collagen (hydroxyproline), the zinc content, and tensile strength of wound tissue. The need to provide vitamin C or zinc supplements after such wound incisions is also discussed.MethodsFull-thickness incision wounds and the ascorbic acid and hydroxyproline levels were measured in 24 rabbits by spectrophotometric methods on day 0 and on the 3rd, 5th, 7th, and 15th days after operation. The tensile strength was measured by a polygraph using a force displacement transducer. The zinc levels of the wounds were measured by atomic absorption spectrophotometry.ResultsThe zinc and hydroxyproline levels reached the peak levels on the 5th day, but the tensile strength of wound increased sharply on the 7th day after wounding while the zinc levels did not change. These results indicated that in the first 7 days of wound healing, high levels of ascorbic acid, hydroxyproline, and zinc cumulation occurred in the wound tissue, and the tensile strength reached its highest level on the 15th day without any supplementation.ConclusionThe supplementation of zinc and/or ascorbic acid should therefore be given just at the beginning of the wounding period, especially if there is deficiency of these nutrients.

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.

THE EFFECTS OF MELATONIN ON HUMORAL IMMUNE RESPONSES OF YOUNG AND AGED RATS

The pineal gland with its effects on immune system and free radicals may have a role on aging process. In this study, we investigated the effects of melatonin (10 mg/kg/d, s.c. for 7 days), the main secretion of the pineal gland, on the humoral immune responses of aged and young male Wistar rats. Eighteen aged (28 months old; 6 in control group and 12 in melatonin group) and 25 young (9 months old; 10 in control group and 15 in melatonin group) rats were given 4×108 sheep erythrocytes i.p. in order to evoke humoral immune responses. After a booster injection at the end of a period of three-weeks following the last melatonin injection, IgM and IgG1 levels were measured. Melatonin was found to increase IgG1 and IgM responses of aged rats when compared to controls (p=0.049 and p=0.007), respectively. In the young rats, while the IgG1 levels of control group were significantly higher than that of the melatonin group (p=0.021), IgM levels were not significantly different (p=0.563). It is concluded that exogenous melatonin may augment the depressed humoral immune responses seen aged 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 EGF on the corneal wound healing of alloxan diabetic mice

We identified the local treatment effect of epidermal growth factor on corneal wound healing of alloxan diabetic mice. The corneal wounds were induced by 0.5 M NaOH solution on the corneal surfaces of the diabetic and non-diabetic groups. The local epidermal growth factor solution (100 ng ml-1) was dropped in 5-microliters aliquots into the eye twice a day. The corneal wounds were measured daily for 15 days and examined histologically at the end of 15th day of experimental period. The results indicated that topical epidermal growth factor treatment of diabetic and non-diabetic mice greatly improved the incidence of healing of wounded corneas.