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Biomedical subjects

Mustafa Gul

Publications and source records attributed to Mustafa Gul.

12 recordsLinked to original sources

Endurance training attenuates exercise-induced oxidative stress in erythrocytes in rat.

The aim of this study was to investigate whether endurance training reduces exercise-induced oxidative stress in erythrocytes. Male rats (n=54) were divided into trained (n=28) and untrained (n=26) groups. Both groups were further divided equally into two groups where the rats were studied at rest and immediately after exhaustive exercise. Endurance training consisted of treadmill running 1.5 h x day(-1), 5 days a week for 8 weeks, reaching the speed of 2.1 km x h(-1) at the fourth week. For acute exhaustive exercise, graded treadmill running was conducted reaching the speed of 2.1 km x h(-1) at the 95th min, 10% uphill, and was continued until exhaustion. Acute exhaustive exercise increased the erythrocyte malondialdehyde level in sedentary but not in trained rats compared with the corresponding sedentary rest and trained rest groups, respectively. While acute exhaustive exercise decreased the erythrocyte superoxide dismutase activity in sedentary rats, it increased the activity of this enzyme in trained rats. On the other hand, acute exhaustive exercise increased the erythrocyte glutathione peroxidase activity in sedentary rats; however, it did not affect this enzyme activity in trained rats. Erythrocyte glutathione peroxidase activity was higher in trained groups compared with untrained sedentary group. Neither acute exhaustive exercise nor treadmill training affected the erythrocyte total glutathione level. Treadmill training increased the endurance time in trained rats compared with sedentary rats. The results of this study suggest that endurance training may be useful to prevent acute exhaustive exercise-induced oxidative stress in erythrocytes by up-regulating some of the antioxidant enzyme activities and may have implications in exercising humans.

Adaptation, Physiological↗

Effects of vinblastine on healing in microvascular anastomosis.

Reconstructive microsurgical procedures are getting more common in cancer patients. Adjuvant therapies, such as chemotherapy, radiotherapy, and immune therapy, are usually combined with surgical approaches to improve outcomes. This study was designed to investigate the effects of preoperative chemotherapy on healing in microvascular anastomosis. As a commonly preferred drug for neoadjuvant cancer treatment, vinblastine was used on rats in our study. Ninety-three Sprague-Dawley rats were used and randomly allocated into two groups as 72 experimental and 21 control rats. Vinblastine 2 mg/kg was administered as a single dose intraperitoneally on day 0 in the experimental group. Leukocytes and erythrocytes were counted on days 0, 1, 3, 5, 7, 10, and 15 in 6 rats of the experimental and 6 rats of the control group. We found that the neutropenia period ended on approximately day 7. After applying the medication, the experimental group (n = 72) was divided into three main groups (n = 24). We performed end-to-end femoral artery anastomosis on days 7 or 14 or 21, respectively, in each group. Each main group was divided into three subgroups (n = 8), and then we tested patency and took biopsies on days 7 or 14 or 21, respectively, in each subgroup. Histopathologic evaluation was carried out. The comparison of patency tests and pathologic examination indicated that there was no statistically significant difference between the two groups.

Anastomosis, Surgical↗

Vitamin E but not Hippophea rhamnoides L. prevented nicotine-induced oxidative stress in rat brain.

Oxidant effects of nicotine in the central nervous system is not clear. The aim of this study was to investigate whether nicotine induces oxidative stress in rat brain, and if it does, to test the effects of Hippophea rhamnoides L. extract (HRe-1) and also vitamin E as a positive control. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine+vitamin E [75 mg/kg/day, intragastric (i.g.)]; nicotine+HRe-1 (250 mg/kg/day, i.g.); and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. Malondialdehyde (MDA) level was increased by nicotine in brain tissue, which was prevented by vitamin E whereas not affected by HRe-1. Brain tissue glutathione S-transferase activities of nicotine administered and HRe-1 supplemented groups were lower than control and vitamin E supplemented groups, while glutathione peroxidase (GSH-Px) activities of vitamin E and HRe-1 supplemented groups were lower than the nicotine administered group. Superoxide dismutase activity was not affected by any of the treatments. Total glutathione level was higher in the vitamin E supplemented group compared with control and nicotine administered groups. Vitamin E might have easily diffused to rat brain as a lipid soluble antioxidant, however, the plant extract, HRe-1, would not have sufficiently diffused to the brain to exert its antioxidant effect.

Animals↗

Cytotoxicity of some azines of acetophenone derived mono-Mannich bases against Jurkat cells.

Acetophenone derived mono-Mannich bases (Ig1-Ig4), 1-aryl-3-amino-1-propanone hydrochlorides, which are known to have cytotoxicity in Jurkat cells, were synthesized. Then, they were converted to corresponding azine derivatives (D1-D4), N, N'-bis(3-amino-1-aryl-propylidene)hydrazine dihydrochlorides, which are bifunctional agents. The aryl part was replaced by phenyl in Ig1, Ig2, Ig3, D1, D2, and D3, and by p-hydroxyphenyl in Ig4 and D4. The amine part was replaced by dimethylamine in Ig1, D1, Ig4 and D4, by piperidine in Ig2 and D2, and by morpholine in Ig3 and D3. The aim of this study was to investigate whether the modification in chemical structure, converting the mono-Mannich base to a corresponding azine derivative, improves the cytotoxicity. In addition, the effect of the representative compound, D3, N, N'-bis(3-morpholine-4-yl-1-phenylpropylidene)hydrazine dihydrochloride, on cellular glutathione level after 1 h exposure in phosphate buffer at 37 degrees C was also determined to provide information on a possible mechanism of cytotoxic action. Compounds D2-D4 are reported for the first time in this study. Except for Ig2 and D2, the cytotoxicity of mono-Mannich bases, Ig1, Ig3 and Ig4 and corresponding azine derivatives, D1, D3 and D4 were higher than the reference compound 5-FU. Azine derivatives D1 and D4 had almost equal cytotoxic potency with corresponding mono-Mannich bases Ig1 and Ig4, respectively. On the other hand, azine derivatives D2 and D3, had 1.28 and 1.90-times less cytotoxicity in Jurkat cells compared with the mono-Mannich bases, Ig2 and Ig3, respectively, from which they are derived. Azine derivative D3 dose-dependently decreased the total cellular glutathione level, suggesting that azine derivatives may exert cytotoxicity by thiol alkylation. Azine derivatives with equal or less cytotoxic potency compared to the mono-Mannich bases they are derived from seemed to be less suitable derivatives for the development of new cytotoxic compounds.

Acetophenones↗

Bacteraemia during tonsillectomy.

The aim of this study was to determine the incidence of bacteraemia during tonsillectomy and investigate the effect of the timing of culture sampling on the incidence of bacteraemia associated with it. Sixty-four consecutive patients who had been admitted for elective tonsillectomy were included in the study. Patients were randomly classified into two groups. Blood cultures as well as tonsillar surface and deep tissue cultures were obtained from all patients before tonsillectomy and 60 minutes after tonsillectomy. In addition, blood cultures were taken within two minutes following tonsillectomy for group 1 and 15 minutes after tonsillectomy for group 2. In group 1, the cultures obtained within two minutes were positive in nine patients, while only two of the blood cultures taken post-operatively were positive in group 2. The difference between the two groups was statistically significant (p < 0.05). The results of this study suggest that a transient bacteraemia occurs frequently in association with tonsillectomy, but the timing of culture sampling for its detection is important.

Adolescent↗

Oxidant/antioxidant status in blood of patients with malignant breast tumour and benign breast disease.

The aim of this study was to investigate the alterations in lipid peroxidation and antioxidant enzyme defences in the blood of patients with malignant breast tumour and benign breast disease. Forty patients with malignant breast tumour, 20 patients with benign breast disease and also 20 healthy control subjects were recruited for the study. Malondialdehyde levels in plasma and erythrocytes, and the activities of erythrocyte CuZn-superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase were measured. Malondialdehyde levels were higher in patients with both benign breast disease and malignant breast tumour compared with control subjects. The activities of all antioxidant enzymes were higher in patients with malignant breast tumour, while only glutathione peroxidase and CuZn-superoxide dismutase activities were higher in patients with benign breast disease. Except for glucose-6-phosphate dehydrogenase, the antioxidant enzymes studied correlated positively with the malondialdehyde levels in patients with malignant breast tumour. On the other hand, only glucose-6-phosphate dehydrogenase activity was increased by the level of malignancy. The activity increases in erythrocyte antioxidant enzymes may be a compensatory upregulation in response to increased oxidative stress especially in patients with malignant breast tumour.

Adult↗

Effects of endurance training on tissue glutathione homeostasis and lipid peroxidation in streptozotocin-induced diabetic rats.

The aims of our study were to assess whether endurance training strengthens glutathione-dependent antioxidant defenses and decreases oxidative stress in experimental diabetes. Streptozotocin-induced diabetic rats were divided into trained and untrained groups, which were further divided into resting and acute exercise groups. Endurance training consisted of treadmill running for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted until exhaustion. Eight weeks' treadmill training increased the endurance, favorably decreased lipid peroxidation as measured by thiobarbituric acid reactive substances but not conjugated dienes levels in kidney and vastus lateralis muscle and upregulated glutathione peroxidase in red gastrocnemius muscle. However, it adversely decreased total glutathione level and glutathione peroxidase activity in kidney. Acute exhaustive exercise up-regulated glutathione peroxidase activity in liver. Endurance training did not prevent the increase in thiobarbituric acid reactive substances level in liver due to acute exhaustive exercise. Activities of glutathione disulfide reductase and glutathione S-transferase were not affected. Even though endurance training appeared to upregulate glutathione dependent antioxidant defense in skeletal muscle and to decrease lipid peroxidation in kidney and vastus lateralis muscle as measured by TBARS, our results suggests that beneficial effects of 8 weeks of endurance training are limited in this rat model of uncontrolled diabetes mellitus.

Analysis of Variance↗

Syntheses and stability studies of some Mannich bases of acetophenones and evaluation of their cytotoxicity against Jurkat cells.

Mannich bases, namely 1-aryl-3-dimethylamino-1-propanone hydrochlorides (Ia-f) as mono-Mannich bases (series I), bis(beta-aroylethyl)ethylamine hydrochlorides (IIa, IIb, IId, IIe) as bis-Mannich bases (series II), 3-aroyl-4-aryl-1-ethyl-4-piperidinol hydrochlorides (series III), which are structural isomers of bis derivatives and some representative quaternary salts (Ig, IIIf, IIIg), were synthesized to investigate the effect of chemical structure and ring substituents on cytotoxic activity in Jurkat cells. Stability studies of some representative compounds have also been realised. Compounds IIb, IId, IIe, and IIIe were reported for the first time. Id-g, IIa, IId, IIe, IIIf,g were 1.25-6.55 times more potent than 5-fluorouracil (CAS 51-21-8). However, the cytotoxic activity of the most potent compounds. Ig and IIIf, were one fifth of that of melphalan (CAS 148-82-3). The formation of compound IV during the stability studies of Ig, IIa, and IIIf suggested that they may be thiol alkylators. Bis-Mannich base IIa in nonsubstituted derivatives, piperidinol derivative IIIb in methyl substituted compounds, mono derivative Id in chloro substituted compounds were the most potent compounds when the cytotoxicity of the compound series which have the same substituents in benzene ring are compared. Replacement of the benzene with thiophene improved the cytotoxicity in both series I and II. Quaternization procedure also increased the cytotoxicity in both series I and III. Quaternary derivatives seem to be promising compounds for further studies to develop new anticancer drugs.

Acetophenones↗

Cytotoxic activities of some mono and bis Mannich bases derived from acetophenone in brine shrimp bioassay.

Some mono Mannich bases (1-phenyl-3-amino-1-propanone salts) and bis Mannich bases (1-phenyl-3-amino-2-amino-methyl-1-propanone salts) derived from acetophenone and a few representative quaternary derivatives were synthesised and their cytotoxicity was tested using the brine shrimp bioassay. This assay may serve as an intermediate test before further in vivo animal experiments in large scale, since brine shrimp nauplii as whole organisms were used in this test. Mono Mannich bases were generally more cytotoxic than their corresponding bis Mannich bases. Mannich bases synthesised were cytotoxic in both brine shrimp bioassay in this study and cell culture tests using Jurkat and Renca cells in a previous study. However, the order of the cytotoxic potency of the compounds were reverse, which may result from faster deamination of bis derivatives than optimal level, and different species and test media used in the two test systems. Faster deamination of bis derivatives might have led to elimination of active metabolites before reaching its target. The cytotoxicity of the compounds might have been altered by amino acids and proteins present in cell culture medium but not in sea water used in brine shrimp bioassay affecting their transport through the cell membrane and metabolism in the cell by binding with the compounds. With higher cytotoxic activity compared with 5-fluorouracil (CAS 51-21-8) in brine shrimp bioassay, mono Mannich base 1 and its quaternary derivative 4 and quaternary bis derivative 8 seem to be candidate compounds for further drug design.

Acetophenones↗

Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E.

The aim of this study was to determine the effects of Hippophae rhamnoides L. extract (HRe-1) and also vitamin E as a positive control on nicotine-induced oxidative stress in rat blood, specifically alterations in erythrocyte malondialdehyde (MDA) level, activities of some erythrocyte antioxidant enzymes, and plasma vitamin E and A levels. The groups were: nicotine (0.5 mg/kg/d, intraperitoneal, i.p.); nicotine+vitamin E (75 mg/kg/d, intragastric, i.g.); nicotine+HRe-1 (1 ml/kg/d, i.g.); and control group (receiving only vehicles). There were 8 rats per group and the supplementation period was 3 weeks. Nicotine-induced increase in erythrocyte MDA level was prevented by both HRe-1 and vitamin E. Nicotine-induced decrease in erythrocyte superoxide dismutase (SOD) activity was prevented by HRe-1, but not vitamin E. HRe-1 increased the erythrocyte glutathione peroxidase (GSH-Px) activity compared with nicotine and the vitamin E groups. Catalase activity was not affected. Vitamin E supplementation increased plasma vitamin E level. Plasma vitamin A level was higher in both vitamin E and HRe-1 supplemented groups compared with nicotine and control groups. The results suggest that HRe-1 extract can be used as a dietary supplement, especially by people who smoke, in order to prevent nicotine-induced oxidative stress.

Animals↗

Serum oxidant/antioxidant status of patients with systemic lupus erythematosus.

The levels of malondialdehyde and ceruloplasmin, and superoxide dismutase activity were higher, while transferrin concentration and the activities of glutathione peroxidase and catalase were lower in serum of patients with systemic lupus erythematosus (n=24) compared with healthy controls (n=20). Disease activity index correlated positively with serum malondialdehyde level (r=0.47, p<0.05), erythrocyte sedimentation rate (r=0.41, p<0.05) and C-reactive protein concentration (r=0.41, p<0.05), while it correlated negatively with serum superoxide dismutase (r=0.42, p<0.05) and glutathione peroxidase (r=-0.44, p<0.05) activities in patients. No such correlations were found in healthy control subjects. It remains to be seen whether correlations found between disease activity score and serum malondialdehyde level, and also activities of serum superoxide dismutase and glutathione peroxidase enzymes observed in the present study may be used to predict prognosis in patients with systemic lupus erythematosus.

Adult↗

Toxicity of some bis Mannich bases and corresponding piperidinols in the brine shrimp (Artemia salina) bioassay.

Some acetophenone-derived bis Mannich bases were synthesized: bis[beta-benzoylethyl]ethylamine hydrochloride (IIa), bis[beta-(p-methylbenzoyl)ethyl]ethylamine hydrochloride (IIb), bis[beta-(p-chlorobenzoyl)ethyl]ethy- lamine hydrochloride (IId), bis[(2-thienylcarbonyl)ethyl]ethylamine hydrochloride (IIe); some corresponding piperidinol derivatives: 3-benzoyl-1-ethyl-4-phenyl-4-piperidinol hydrochloride (IIIa), 1-ethyl-3-(p-methyl- benzoyl)-4-(p-methylphenyl)-4-piperidinol hydrochloride (IIIb), 1-ethyl-3-(p-methoxybenzoyl)-4-(p-methoxy- phenyl)-4-piperidinol hydrochloride (IIIc), 1-ethyl-3-(p-chlorobenzoyl)-4-(p-chlorophenyl)-4-piperidinol hydrochloride (IIId), 1-ethyl-4-(2-thienyl)-3-(2-thienylcarbonyl)-4-piperidinol hydrochloride (IIIe); and some representative quaternary piperidinols: 3-benzoyl-1-ethyl-4-hydroxy-1-methyl-4-phenylpiperidinium iodide (IIIf), 1-ethyl-4-hydroxy-1-methyl-3-(p-methylbenzoyl)-4-(p-methylphenyl)piperidinium iodide (IIIg). Toxicity was tested by the brine shrimp bioassay as an intermediate test before further in vivo animal experiments. Piperidine derivatives were found to be more potent than bis Mannich bases. Quaternary piperidine derivatives IIIf and IIIg and also non-quaternary piperidine derivatives IIIb, IIIe, IIIc and IIId were more toxic than 5-fluorouracil in brine shrimp bioassay. Except for IIe, bis Mannich bases were not effective. Quaternization and conversion of bis Mannich bases to corresponding piperidines improved the toxicity. The lipid solubility of the compounds may not affect the toxicity. From these findings the quaternary piperidine derivatives IIIf and IIIg could be used in further drug development and also for in vivo experiments.

Acetophenones↗