Halide Edip Temel

Supplemental Carvacrol Can Reduce the Severity of Inflammation by Influencing the Production of Mediators of Inflammation

ABSTRACTCarvacrol (CVC) is a monoterpenic phenol, which is present in the essential oil of various plants. It has been widely used both as antibacterial feed additive and food preservative. Therefore, our objective was to evaluate the prophylactic effects of carvacrol on inflammatory mediators of sepsis. Serum tumor necrosis factor alpha and interleukin 6 levels as proinflammatory markers were evaluated using an enzyme-linked immunosorbent assay technique. Malondialdehyde (MDA) was determined in the sample by using thiobarbituric acid test. Nitric oxide (NO) levels and arginase activity and also all measurements were evaluated after 24 h from lipopolysaccharide (LPS) injections done (1 mg/kg i.p.). All carvacrol doses (20, 40, and 80 mg/kg) were given by intra gastric gavage during six days before LPS injection (7th day). Proinflammatory cytokines, MDA, NO levels, and arginase activity were decreased by carvacrol according to the carvacrol doses. These results indicate that carvacrol may have a potent anti-inflammatory and antioxidant effects in a dose-dependent manner. Subchronic use of CVC can be assisted to pre-treat of sepsis as a prophylactic.

Synthesis and Biological Evaluation of Some Pyrazoline Derivatives Bearing a Dithiocarbamate Moiety as New Cholinesterase Inhibitors

In the present study, new pyrazoline derivatives were synthesized via the reaction of 1‐(chloroacetyl)‐3‐(2‐furyl)‐5‐aryl‐2‐pyrazolines with sodium salts of N,N‐disubstituted dithiocarbamic acids. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellmans spectrophotometric method. The compounds were also investigated for their cytotoxic properties using the MTT assay. The most potent AChE inhibitor was found as compound 7 followed by compounds 27 and 17, when compared with eserine. Compounds effective on AChE carry the 2‐dimethylaminoethyl moiety, which resembles the trimethylammonium group and the ethylene bridge of acetylcholine. Among all compounds, compound 7 bearing 2‐dimethylaminoethyl and 3,4‐methylenedioxyphenyl moieties was also found to be the most effective inhibitor of BuChE. The MTT assay indicated that the effective concentration of compound 7 was lower than its cytotoxic concentration.

The effects of captopril and losartan on erythrocyte membrane Na+/K+- ATPase activity in experimental diabetes mellitus

Diabetes mellitus induces a decrease in sodium potassium-adenosine triphosphatase (Na+/K+- ATPase) activity in several tissues in the rat and red blood cells (RBC) and nervous tissue in human patients. This decrease in Na+/K+- ATPase activity is thought to play a role in the development of long term complications of the disease. Angiotensin enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARBs) reduce proteinuria and retard the progression of renal failure in patients with IDDM and diabetic rats. We investigated the effects of captopril and losartan, which are used in the treatment of diabetic nephropathy, on Na+/K+- ATPase activity. Captopril had an inhibitory effect on red cell plasma membrane Na+/K+ ATPase activity, but losartan did not. Our study draws attention to the inhibitory effect of captopril on Na+/K+ ATPase activity. Micro and macro vascular complications are preceeding mortality and morbidity causes in diabetes mellitus. There is a strong relationship between the decrease in Na+/K+ ATPase activity and hypertension. The non-sulphydryl containing ACEi and ARBs must be the choice of treatment in hypertensive diabetic patients and diabetic nephropathy.

Synthesis and Anticholinesterase Activity and Cytotoxicity of Novel Amide Derivatives

In the present study, some amide derivatives were synthesized and their potential anticholinesterase properties were investigated. N‐(Benzothiazol‐2‐yl)‐2‐[(5‐amino/methyl‐1,3,4‐thiadiazol‐2‐yl)thio]acetamide derivatives were obtained by nucleophilic substitution of 2‐chloro‐N‐(benzothiazole‐2‐yl)acetamide derivatives with appropriate 1,3,4‐thiadiazole‐2‐thioles. The chemical structures of the compounds were elucidated by 1H‐NMR, 13C‐NMR and FAB+‐MS spectral data and elemental analyses. Each amide derivative was evaluated for its ability to inhibit AChE and BuChE using a modification of Ellmans spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. 2‐(5‐Amino‐1,3,4‐thiadiazol‐2‐yl)thio‐N‐(benzothiazol‐2‐yl)acetamide derivatives have anticholinesterase activity, whereas 2‐(5‐methyl‐1,3,4‐thiadiazol‐2‐yl)thio‐N‐(benzothiazol‐2‐yl)acetamide derivatives have no inhibitory effect on enzyme activity. Among these compounds, it is clear that compound IIh is the most potent derivative.

Oxidative stress-mediated myocardiotoxicity of ciprofloxacin and ofloxacin in juvenile rats.

In this study, evaluation of the myocardiotoxic effect potential of ciprofloxacin and ofloxacin in juvenile rats and the role of oxidative stress in heart toxicity was conducted. Doses (25 and 50 mg/kg) of each drug were administered to the rats for 1 week. Serum biochemical cardiotoxicity parameters and tissue malondialdehyde and nitric oxide levels were measured. All measured parameters were found elevated in the drug-treated rats, being the highest in the 50-mg/kg ofloxacin-treated rats. Ciprofloxacin and ofloxacin may cause myocardiotoxicity by inducing the oxidative stress in the heart, and nitric oxide is partly responsible for this toxicity.

Chemical Composition and Biological Activity of Haplophyllum tuberculatum Juss. Essential Oil

Abstract: The essential oil of Haplophyllum tuberculatumwas prepared by hydrodistillation of the fresh flowering aerial parts of the plant collected from Saudi Arabia. The oil was subsequently analyzed by GC and GC-MS. Thirty seven compounds, accounting for 96.4 % of the oil composition were identified. The major components were trans-p-menth-2-en-1-ol (19.2 %), cis-p-menth-2-en-1-ol (13.2 %), myrcene (10.1 %), δ-3- carene (8.8 %), β-phellandrene (6.9 %), limonene (6.6 %) and cis-piperitol (6.4 %). The antimicrobial activity of the essential oil was determined using the broth microdilution method against various human pathogens, where a relatively low inhibitory range was observed (MIC 1 mg/mL). Furthermore, the oil was evaluated for its antifungal activity against the strawberry anthracnose-causing fungal plant pathogens Colletotrichum acutatum, C. fragariae and C. gloeosporioides using the direct overlay bioautography assay. The essential oil showed no antifungal activity at 80 and 160 µg/spot concentrations compared to commercial antifungal standards. The oil was also investigated for its insecticidal and repellent activity against Aedes aegypti. The oil was repellent to the yellow fever mosquito Ae. aegypti using the “cloth patch assay” down to a concentration of 0.074 mg/cm2; however, the oil had low toxicity against first instar larvae and adults of Ae. aegypti in a high throughput larval bioassay and adult topical assay. Additionally, enzyme activity was measured using the spectrophotometric Ellman method. The oil showed weakly acetylcholinesterase (AChE) inhibitory activity at the tested concentration, compared to standard substances, whereas no inhibition on butyrylcholinesterase (BuChE) activity was observed.

Apoptotic effects of some carbazole derivatives on lung carcinoma and glioma cell lines

In this study, we aimed to study the apoptotic effects of 2-[(9-ethyl-9H-carbazol-3-yl)amino]-2-oxoethyl N,N-disubstituted dithiocarbamates on A549 lung carcinoma and C6 glioma cell lines. Cytotoxicity analyses of DNA synthesis and detection of apoptosis by flow cytometry were evaluated to determine the anticancer activity of the compounds on both cell lines. Compounds 2, 5, and 7 which exhibited significant cytotoxic activity in MTT assay were chosen for flow cytometric analyses to determine the apoptotic percent of cells. These compounds also exhibited better DNA synthesis inhibition activity on cancer cells. Finally, acetylcholinesterase inhibition potentials of the compounds were measured. Compound 7 carrying 4-(2-dimethylaminoethyl)piperazin-1-yl moiety was the most active apoptotic agent against A549 and C6 cells. Apoptotic effect of this compound can be attributed to its AchE inhibition activity. Compounds 2 and 5 also showed apoptotic effects on C6 glioma cell lines. Compounds 2, 5, and 7 can be identified as the most promising anticancer agents against A549 and C6 cancer cell lines.

Effects of Lipoprotein-Associated Phospholipase A2 on Arginase/Nitric Oxide Pathway in Hemodialysis Patients

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and arginase are recently described inflammatory biomarkers associated with cardiovascular disease. In this study, we aimed to investigate the possible effects of serum Lp-PLA2 mass levels on arginase/nitric oxide (NO) pathway as a cardiovascular risk marker in hemodialysis (HD) patients. Forty-three HD patients and 15 healthy subjects were included in this study. Lipid profile, high sensitivity C-reactive protein (hs-CRP), albumin, creatinine, body mass index (BMI), Lp-PLA2 and total nitrite levels, and arginase activity were determined in serum samples from patients and control subjects. Lp-PLA2 levels were found to be positively correlated with arginase, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and age and negatively correlated with high-density lipoprotein-cholesterol and total nitrite levels, while there was no correlation with BMI and hs-CRP, albumin, and creatinine levels in HD patients. We conclude that elevated Lp-PLA2 mass levels may contribute to impaired arginase/NO pathway in HD patients and that increased the arginase activity and Lp-PLA2 mass levels with decreased total nitrite levels seem to be useful biochemical markers in terms of reflecting endothelial dysfunction and associated cardiovascular risks in HD patients.

Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents.

New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1′-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases.

Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors

In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl]thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by 1H NMR, 13C NMR and mass spectral data and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman’s spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. The most potent AChE inhibitor was found as compound 4e (IC50 = 25.5 ± 2.12 µg/mL) followed by compounds 4i (IC50 = 38.50 ± 2.12 µg/mL), 4c (IC50 = 58.42 ± 3.14 µg/mL) and 4g (IC50 = 68 ± 2.12 µg/mL) when compared with eserine (IC50 = 0.025 ± 0.01 µg/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC50 > 80 µg/mL). MTT assay indicated that the cytotoxic dose (IC50 = 71.67 ± 7.63 µg/mL) of compound 4e was higher than its effective dose.