Effects of limited food intake and vitamin C supplementation on pancreatic glucagon and insulin in guinea pigs.

The aim of this study was to investigate the effects of limited food intake (LFI) (24, 48 and 120 h) and a single i.p. dose of vitamin C supplementation (500 mg/kg) on serum glucose and C-peptide levels, and pancreatic insulin and glucagon levels in guinea pigs. The highest serum glucose levels were found after vitamin C supplementation plus LFI for 48 h (LFI 48). Serum C-peptide levels were not significantly affected by food limitation (LFI 24, LFI 48, or LFI 120) as compared with controls, but when vitamin C was supplemented, the C-peptide levels were moderately enhanced. Immunohistochemical findings on pancreatic islets showed increased staining intensity for both insulin and glucagon when vitamin C was supplemented. In addition, the alpha and beta cells were stimulated, particularly by vitamin C supplementation plus LFI 120. Based on these findings, vitamin C supplementation may have a beneficial effect on the alpha and beta cells.

The effects of dexfenfluramine administration on brain serotonin immunoreactivity and lipid peroxidation in mice.

Obesity continues to be an increasing health problem in worldwide and antiobesity drugs have commonly been used by obese patients. During the use of anorectic drugs, the antioxidant defense may be affected, especially by reactive oxygen species. It was decided to investigate the effects of dexfenfluramine on body weight, daily food intake, brain thiobarbituric acid-reactive substances (TBARS), glutathione (GSH) and nitric oxide (NO) levels, and 5-HT immunoreactivity. Mice were divided into two groups each containing 8 Swiss Albino adult (6 months) mice. Group 1, untreated, was used as a control; group 2 was treated with dexfenfluramine 0.4 mg/kg per day intraperitoneally for 7 days. Brain TBARS and GSH levels were assayed spectrophotometrically. The stable end-products of NO, nitrite and nitrate, were analyzed spectrophotometrically. Brain tissue 5-HT immunoreactivity was observed using an immunohistochemical method. There were significant decreases in body weight in the dexfenfluramine group (p < 0.05). Although brain GSH and NO(x) levels decreased significantly, brain TBARS levels increased in the dexfenfluramine group (p < 0.05). Brain 5-HT immunoreactivity also increased in the dexfenfluramine-treated group compared to control. In conclusion, our findings show that dexfenfluramine is effective in achieving weight loss and also increases lipid peroxidation in mouse brain.

The effect of tryptophan administration on ileum contractility and oxidant status in mice.

L-tryptophan (TRP) is the precursor amino acid for the synthesis of serotonin (5-HT). 5-HT is effective both on the food intake and gastrointestinal system contractility. The aim of this study was to search the effects of systemic TRP treatment on 5-HT levels of ileum and searching the effect of ileal contractility and oxidant status. Swiss-albino mice were divided into two groups: 1. Control, 2. TRP-treated (100 mg/kg/24 h, i.p., for 7 days). Body weights were recorded at the beginning and at the end of experiments. Acetylcholine-induced contractile responses in the isolated ileum were recorded on polygraph. Ileal tissue malondialdehyde and glutathione levels determined by spectrophotometric and ileal tissue 5-HT levels were measured by immunohistochemical methods. TRP treatment decreased body weight and increased ileal contractile response. In the TRP-treated group, ileum malondialdehyde levels increased and glutathione levels decreased. Immunohistochemical detection showed that ileal 5-HT levels were increased by TRP treatment. There is a relationship between increased oxidative stress and increased contractility in the ileal tissue of the TRP-treated animals. These effects may be related to increased ileal 5-HT synthesis.

Effects of vitamin C on muscle glycogen and oxidative events in experimental diabetes.

UNLABELLED: Streptozotocin (STZ) is an agent used in creating experimental diabetes. Varying findings have been reported about the striated muscle glycogen levels in diabetes. In this study, it was planned to observe interaction of vitamin C (AA), of which deficiency has been shown in diabetics, with soleus muscle glycogen levels and oxidative events on STZ-diabetic subjects. MATERIAL AND METHOD: In the study, 38 male adult Wistar Albino rats with weights 200 +/- 20 g were used by separating them into four groups: Control, Vitamin C, Diabetes, Diabetes + Vitamin C. Body weights and fasting blood glucose were measured at the beginning and end of the experiment. AA, TBARS, GSH, NOx and glycogen levels of soleus muscles, and AA level of blood were measured. The results were compared using Anova variance and Mann-Whitney U tests. Results showed that AA levels in blood increased with vitamin C administration; AA, GSH and NOx levels in the muscle were low and MDA and glycogen levels were high in diabetics; and that vitamin C in the given dosage partially corrected these values. These results indicate that higher dosage than daily 20 mg/kg Vitamin C is required for being effective on metabolic and oxidizing events in diabetic rats.

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

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.

Tryptophan administration increase contractility and change the ultrastructure of mice duodenum.

Serotonin (5-HT) is a metabolite of tryptophan (TRP). 5-HT has been shown to induce contractions in rat duodenum and ileum. We planned to investigate the in vivo effects of TRP administration on duodenal contractility and ultrastructure together. Two equal groups of adult male Swiss-albino mice were used in the experiments. Controls (CONT) and TRP treated (100 mg/kg/24 hr in 0.2 ml. saline solution ip, 7 days). Body weights were recorded at the beginning and at the end of experiments. Duodenum tissues contractility responses to different concentration of KCl and acethycholine (ACh) were recorded on polygraph. The ultrastructural changes in duodenum observed by transmission electron microscopic (TEM) method and 5-HT levels determined by immunohistochemical method. Body weights decreased and duodenal contractile response of ACh increased significantly by TRP treatment. The duodenal ultrastructural changes in TRP group illustrated partially loss of apical surface and fusion in microvilli. Immunohistochemical detection showed that 5-HT increased by TRP treatment. There is a relation between duodenal contractility increased by TRP treatment and changes in the duodenal tissue 5-HT level and ultrastructure.

The healing effect of TGF-alpha on gastric ulcer induced by acetylsalicylic acid in rats.

The present study was designed to investigate the effects of microemulsion and aqueous solution containing transforming growth factor alpha (TGF-alpha) and/or aprotinin administered intragastrically (i.g.) on healing of acute gastric ulcers induced by acetylsalicylic acid (ASA). The microemulsion was prepared by modification of the microemulsion formulation described in our previous study. Acute gastric lesions were induced by the application of ASA (150 mg/kg in 1.5 ml of 0.2N HCl i.g.). TGF-alpha in solution or microemulsion formulations were administered at a dose of 10 microg/kg per 24h i.g. for 2 days. The effects of TGF-alpha on the healing was evaluated with the measurement of ulcer score, basal gastric acid secretion, total protein content of gastric fluid, gastric mucus level and histological analysis. The results indicated that the highest decrease in ulcer area was observed in group treated with microemulsion containing TGF-alpha plus aprotinin (TA-ME). TGF-alpha in microemulsion formulation was more effective than TGF-alpha in solution formulation in the increase of gastric mucus secretion, in the decrease of gastric acid secretions and ulcer scores. Histological evaluation of the gastric mucosa samples revealed that, best recovery was obtained in the TA-ME treated group.

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 x 10(8) 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.

Effects of epidermal growth factor in artificial tear on vitamin C levels of corneal wounded eye tissues.

PURPOSE: To investigate the effect of artificial tear (AT) solution and epidermal growth factor (EGF) treatment on the cornea and aqueous humour ascorbic acid (AA) levels of full-thickness corneal wounded eyes. METHODS: The effect of EGF on the AA levels of aqueous humour and corneal wound tissue was determined in full-thickness corneal wounded rabbit eyes on the seventh post-operative day. There were three groups: untreated controls, AT-treated controls and an EGF+AT-treated experimental group (n = 6 in each group). Corneal wounded eyes were topically treated with 5 microl AT or 5 microl EGF in AT (1 mg/l EGF in AT prepaaration which contained 3.0% carbopol 940) twice daily for 6 days after operation. The wound strengths were also measured on the seventh post-operative day as a measure of wound healing. Statistical analysis was carried out using the Mann-Whitney U-test by Statview program. RESULTS: The wound strengths of corneas, and AA levels of wound tissues and aqueous humour, increased significantly following AT and EGF treatment (p < 0.05). CONCLUSION: In the corneal wounded eye, aqueous humour serves as a source of vitamin C and there may be a relation between EGF treatment in AT and AA levels of corneal wounded eye tissues.

The effect of granulocyte macrophage-colony stimulating factor on glutathione and lipid peroxidation in a rat model.

AIMS: Irradiation decreases incisional healing and produces oxygen radicals that damage cells. Because of the lipid component in the membrane, lipid peroxidation is reported to be particularly susceptible to radiation damage. Glutathione acts as a cosubstrate in the enzymatic repair of radiation damage. The aim of this study is to examine the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in incisional skin wounds by investigating lipid peroxidation and reduced glutathione levels in the irradiated rats. METHODS: Rats were irradiated with cobalt 60 and a dorsal skin incision was made 2 days after irradiation. Rats were divided into four groups: group 1: control; group 2: GM-CSF administered; group 3: irradiated control group; group 4: irradiated and GM-CSF administered group. RESULTS: By irradiation, a marked lipid peroxidation increase was demonstrated. Two days after irradiation, in animals given total body irradiation (TBI), application of a single topical dose of GM-CSF decreased lipid peroxidation of the tissue decreased significantly. By drug administration, the GSH content of the skin increased both in the irradiated and non-irradiated groups. CONCLUSIONS: Our results suggest that GM-CSF modulate lipid peroxidation and GSH of the skin wound.

Effects of vitamin C supplementation on plasma antioxidant status in unfed periods.

In this study, the antioxidant protection of ascorbic acid (AA) supplementation during different unfed periods (24, 48, 120 h) was determined with blood lipid peroxidation level (thiobarbituric acid reactive substances, TBARS) and compared with plasma antioxidant sulfydryl group (RSH) content. Weight loss was induced by increasing the unfed period together with vitamin C supplementation. Blood AA levels decreased by starvation but increased by vitamin C supplementation. RSH content in plasma also decreased with the unfed period; these decreases became apparent by vitamin C supplementation. TBARS formation increased significantly by AA supplementation in the 120-h starvation period.

Effects of epidermal growth factor dosage forms on mice full-thickness skin wound zinc levels and relation to wound strength.

Epidermal growth factor (EGF) and zinc promote re-epithelization and reparative tissue strength by enhancing deposition of collagen at the site of the wound. In this study two EGF dosage forms were chosen to assess the effect of zinc levels on wound healing and for comparison with wound tear strengths. A solution of EGF in 0.9% w/v NaCl and an EGF gel in 0.2% Carbopol 940 polymer (5 microL) were applied to full-thickness skin wounds of mice twice a day for 7 and 15 days. Wound zinc levels were higher on day 7 than on day 15, especially in wounds treated with EGF. The wound zinc levels of the gel + EGF group on day 15 were similar to those of normal control skin. These results imply that there is a close connection, but no direct relationship, between EGF application in both dosage forms and wound zinc levels during healing.

The effects of artificial tear solutions on wound healing in full thickness corneal incisions.

Carbopols (carbomer, polyacrylic acid) are appropriate for ophthalmic use as an artificial tear in the form of viscous aqueous solutions. Carbopol 940 preparations were developed as long-lasting artificial tears for the relief of dry eye syndrome and traumatic injury. We identified the 15 days local treatment effects of two artificial tear solutions by wound strength and histologic examination of the incision wounds of rabbit corneas by comparing these results with the controls. Three layers of control corneas were regular. The untreated but wounded corneas epithelium and stroma were completely irregular. Both treated eyes had thinner epithelization in the incision site compared to control unwounded eye. Wounds treated with A preparation (viscotiers) had vocuoles and numerous inflammatory cells and remarkable oedematous regions but B preparation (Thilo-Tears) treated wounds had inflammatory cells and oedematous regions less than the other group. The wound strengths of gel treated wounds were bigger than those of controls. A considerable result in wound strength and better wound healing was also obtained in B preparation treated group because of the arrangement of the pH and tonicity at the Thilo-tears gel preparation.

Epidermal growth factor and glucocorticoid effects on blood prostaglandin E2 level in DENA-induced carcinogenesis.

This paper describes results on carcinogenesis in rats induced with diethylnitrosamine (DENA; 280 mg/kg single dose, i.p.). After inducing chemical carcinogenesis, the animals were treated with different compounds that affect cell proliferation and the effects on the blood prostaglandin E2 (PGE2) levels were observed. These compounds were epidermal growth factor (EGF, 10 micrograms/kg/24 h i.p., 7 days) and dexamethasone (4 mg/kg/24 h i.p., 7 days). The blood PGE2 levels of rats were measured by RIA (Radioimmunoassay). The blood PGE2 levels increased significantly following DENA and EGF administrations alone or together. Dexamethasone administration decreased the blood PGE2 levels. In conclusion the data show that the increase in the plasma PGE2 level by DENA treatment was enhanced by EGF but opposed by dexamethasone. This suggests that EGF may be effective as a promoter in chemical carcinogenesis.

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.

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

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 microL 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).

Effects of epidermal growth factor on serum zinc and plasma prostaglandin E2 levels of mice with pressure sores.

This work was undertaken to study the effects of systemic application of EGF on the plasma PGE2 and serum zinc levels of mice with pressure sores. The pressure sores were made on the hind limb of the mice by bilateral sciatic nerve neurotomy. Mice were injected IP, 1 microgram EGF daily for ten days, beginning on the 21st day after operation. EGF administration increased the serum zinc and plasma PGE2 levels compared with controls. These results indicate that EGF can be effective on wound healing by elevating the serum zinc and plasma PGE2 concentrations together with other physiological roles in cellular events.