Yeliz Demir

Changes in the anti-oxidant system in adult epilepsy patients receiving anti-epileptic drugs

Abstract Anti-epileptic drugs (AEDs) have been widely used in patients with epilepsy. This study evaluated the adverse effects of two commonly prescribed AED monotherapies, carbamazepine (CBZ) and valproic acid (VPA). The aim of this study was to evaluate the influence of these anti-epileptic drugs on paraoxonase-1 (PON-1), glutathione S-transferase (GST) and acetyl cholinesterase (AChE) activities in the serum of adult patients with epilepsy. Of the 56 epileptic adults, 28 were given valproate, and the remaining 28 were given carbamazepine. Glutathione (GSH) levels in epilepsy patients receiving anti-epileptic drug treatment were insignificantly higher compared with controls. GST activity in epilepsy patients receiving anti-epileptic drug treatment was insignificantly lower compared with controls. PON1 and AChE activity in epilepsy patients receiving anti-epileptic drug treatment was significantly lower compared with controls. PON1 and AChE activities in the serum of patients treated with carbamazepine monotherapy were lower than in patients treated with valproic acid monotherapy.

In vivo changes in carbonic anhydrase activity and histopathology of gill and liver tissues after acute exposure to chlorpyrifos in rainbow trout

Abstract Chlorpyrifos is an organophosphate pesticide widely used in agriculture and aquaculture. This study investigated its effects on carbonic anhydrase (CA) enzyme activity and histopathology of rainbow trout gill and liver. The fish were exposed to 2.25 (25 % of 96 h LC50), 4.5 (50 % of 96 h LC50), and 6.75 μg L-1 (75 % of 96 h LC50) of chlorpyrifos for 24, 48, 72, and 96 h. CA activity was measured in liver and gills and histopathological changes were examined by light microscopy. The most common liver changes at most of the chlorpyrifos concentrations were hyperaemia and degenerative changes. Gill tissues were characterised by lamellar hyperaemia, lamellar oedemas, clumping, cellular degeneration, hyperplasia, and lamellar atrophy. CA enzyme activity in the gills decreased at all concentrations at 48, 72, and 96 h after exposure to chlorpyrifos (p<0.05). Similarly, there was a time-dependent decrease in CA activity at all of the concentrations in liver tissues (p<0.05). The present study indicated that chlorpyrifos inhibits CA enzyme activity and causes histopathological damage in gill and liver tissues Sažetak Klorpirifos je organofosforni pesticid široke primjene u poljoprivredi i ribarstvu. U ovome radu istražili smo njegov učinak na aktivnost enzima ugljikove anhidraze te histopatologiju škrga i jetre u kalifornijske pastrve. Ribe su bile izložene klorpirifosu u koncentracijama 2,25 μg L-1 (25 % 96-satnog LC50), 4,5 μg L-1 (50 % 96-satnog LC50) i 6,75 μg L-1 (75 % 96-satnog LC50) tijekom 24, 48, 72 i 96 sati. Aktivnost ugljikove anhidraze mjerena je u jetri i škrgama, a histopatološke promjene promatrane su svjetlosnom mikroskopijom. Najčešće promjene u jetri pri većini koncentracija bile su hiperemija i degenerativne promjene. Na tkivu škrga primijećeni su hiperemija i edemi u škržnim listićima, sljepljivanje i degeneracija stanica, hiperplazija te atrofija škržnih listića. Aktivnost ugljikove anhidraze u škrgama smanjila se pri svim koncentracijama nakon 48, 72 i 96 sati izloženosti (p<0.05). Također je uočeno i smanjenje aktivnosti ugljikove anhidraze u jetri ovisno o duljini izloženosti pri svim koncentracijama (p<0.05). Dobiveni rezultati upućuju na to da klorpirifos inhibira aktivnost ugljikove anhidraze i izaziva značajna histopatološka oštećenja u škrgama i jetri

Antiepileptic drugs: Impacts on human serum paraoxonase‐1

Serum paraoxonase (PON1) is a key enzyme related to high‐density lipoprotein (HDL)‐cholesterol particle. It can prevent the oxidation of low‐density lipoprotein (LDL) and HDL. The present article focuses on the in vitro inhibition role of some antiepileptic drugs (AEDs) such as valproic acid, gabapentin, primidone, phenytoin, and levetiracetam on human paraoxonase (hPON1). Therefore, PON1 was purified from human serum with a specific activity of 3976.36 EU/mg and 13.96% yield by using simple chromatographic methods. The AEDs were tested at various concentrations, which showed reduced in vitro hPON1 activity. IC50 values for gabapentin, valproic acid, primidone, phenytoin, and levetiracetam were found to be 0.35, 0.67, 0.87, 6.3, and 53.3 mM, respectively. Ki constants were 0.261 ± 0.027, 0.338 ± 0.313, 0.410 ± 0.184, 10.3 ± 0.001, and 43.01 ± 0.003 mM, respectively. Gabapentin exhibited effective inhibitory activity as compared with the other drugs. The inhibition mechanisms of all compounds were noncompetitive.

Phenolic compounds inhibit the aldose reductase enzyme from the sheep kidney

Aldose reductase (AR) is the key enzyme for the polyol pathway and responsible for sorbitol accumulation during the hyperglycemia. The present article focuses on the role of phenol, pyrogallol, hydroquinone, resorcinol, catechol, and phloroglucinol in in vitro inhibition of AR. For this purpose, AR was purified from the sheep kidney with 5.33 EU mg−1 specific activity and 0.64% yield using several chromatographic methods. Various concentrations of the compounds were tested on in vitro AR activity. IC50 values were found for phenol, pyrogallol, hydroquinone, resorcinol, catechol, and phloroglucinol as 6.5, 1.13, 5.45, 2.21, 1.8, and 2.09 mM, respectively, and their Ki constant was calculated as 3.45 ± 0.92, 0.96 ± 0.28, 3.07 ± 0.46, 1.59 ± 0.43, 2.5 ± 0.35, and 2.54 ± 0.45 mM, respectively. Pyrogallol showed better inhibitory effect compared to the other compounds. The inhibition mechanisms of all compounds were noncompetitive. In the presents study, in vitro AR inhibition was examined by the phenolic compounds.

Some metals inhibit the glutathione S-transferase from Van Lake fish gills

Glutathione S‐transferases (GSTs) are the superfamily of multifunctional detoxification isoenzymes and play important role cellular signaling. The present article focuses on the role of Cd2+, Cu2+, Zn2+, and Ag+ in vitro inhibition of GST. For this purpose, GST was purified from Van Lake fish (Chalcalburnus tarichii Pallas) gills with 110.664 EU mg−1 specific activity and 79.6% yield using GSH‐agarose affinity chromatographic method. The metal ions were tested at various concentrations on in vitro GST activity. IC50 values were found for Cd+2, Cu+2, Zn+2, Ag+ as 450.32, 320.25, 1510.13, and 16.43 μM, respectively. Ki constants were calculated as 197.05 ± 105.23, 333.10 ± 152.76, 1670.21 ± 665.43, and 0.433 ± 0.251 μM, respectively. Ag+ showed better inhibitory effect compared with the other metal ions. The inhibition mechanisms of Cd2+ and Cu2+ were non‐competitive, whereas Zn2+ and Ag+ were competitive. Co2+, Cr2+, Pb2+, and Fe3+ had no inhibitory activity on GST.

Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia

Diabetes mellitus (DM) is a chronic metabolic disease in which there are high blood sugar levels over a prolonged period. Aldose reductase (AR) belongs to aldo-keto reductase superfamily and plays a key role in the polyol pathway. α-Glycosidase and α-amylase are important enzymes in glucose metabolism. In this study, AR was purified from purified from cow liver. The enzyme was obtained with 139.17 purification fold and with a specific activity of 1.67 EU/mg protein. Then, it is observed the inhibition effect of diarylmethanons (1a-d), bromophenols (2a-d and 4a-d) and diarylmethanes (3a-d) on aldose reductase, α-glycosidase and α-amylase enzymes. In these series, compound 2a showed lowest inhibitory activity against AR with a Ki value of 1.09 ± 0.29 μM while compound 2d showed highest inhibitory activity against AR with a Ki value of 0.092 ± 0.015 μM. Additionally, α-glycosidase and α-amylase enzymes were easily inhibited by these compounds. All compounds were tested for their inhibition effects against of α-glycosidase enzyme and demonstrated efficient inhibition profiles with Ki values in the range of 14.44 ± 0.88-43.53 ± 9.06 nM, and IC50 values in the range of 11.72-46.11 nM. Also, inhibition of the α-amylase enzyme, which determined an effective inhibition profile with IC50 values, is in the range of 3.84-29.61 nM.

The behavior of some chalcones on acetylcholinesterase and carbonic anhydrase activity

Abstract Carbonic anhydrase (CA) has a key role in respiration, carbon dioxide and bicarbonate transport. Acetylcholinesterase (AChE) is a serine hydrolase and mostly abundant at neuromuscular junctions and cholinergic brain synapses. Inhibitors of these enzymes could aid in illuminating the role in disease processes. In this study, we separately purified CA I and CA II from human erythrocytes. The purity of the enzymes was showed by SDS-PAGE analysis. We also investigated the inhibition of seven chalcones toward hCA I, hCA II, and AChE. The chalcones were effective inhibitors of the cytosolic CA isoforms (hCA I and hCA II) and AChE with Ki values in the range of 1.83–7.05 μM for hCA I, 0.59–5.50 μM for hCA II, and 0.61–86.11 μM for AChE. All compounds were showed competitive inhibition aganist both enzymes. These compounds can be a potent inhibitor of AChE enzyme and both cytosolic CA isoenzymes which are commonly used in the pharmaceutical and medical industries.

Phytase from Weissella halotolerans: purification, partial characterisation and the effect of some metals

ABSTRACT In the study, phytase was purified in three simple steps comprising ammonium sulphate precipitation, anion exchange and gel filtration chromatography from Weissella halotolerans. The enzyme was obtained with a specific activity of 227.73 EU/mg and 6.52% recovery. The molecular mass of the enzyme was determined to be 41.52 kDa. The optimum pH and temperature for the enzyme were 6.0 and 50°C, respectively. Furthermore, the effects of metal ions on the enzyme were investigated. Ag+, Zn2+, Cr2+ and Fe2+ ions inhibited phytase by 21.86, 25.63, 32.82 and 90.43%, respectively, whereas Co2+, Cu2+, Pb2+, Cd2+ ve Mn2+ ions increased the enzyme activity.

Inhibition effects of pesticides on glutathione-S-transferase enzyme activity of Van Lake fish liver

Glutathione‐S‐transferases (GSTs) have a function in xenobiotic metabolism. They are a significant multifunctional family with a wide variety of catalytic activities. In the current study, we determined in vitro inhibition effects of 2,4‐dichlorophenoxyacetic acid dimethylamine salt (2,4‐D DMA), haloxyfop‐P‐methyl, glyphosate isopropylamine, dichlorvos, and λ‐cyhalothrin on purified GST. For this purpose, GST were purified from Van Lake fish (Chalcalburnus tarichii Pallas) liver with 29.25 EU mg−1 specific activity and 10.76% yield using GSH–agarose affinity chromatographic method. The pesticides were tested at various concentrations on in vitro GST activity. Ki constants were calculated as 0.17 ± 0.01, 0.25 ± 0.05, 3.72 ± 0.32, 0.42 ± 0.06, and 0.025 ± 0.004 mM, for 2,4‐D DMA, haloxyfop‐P‐methyl, glyphosate isopropylamine, dichlorvos, and λ‐cyhalothrin, respectively. λ‐Cyhalothrin showed a better inhibitory effect compared to the other pesticides. The inhibition mechanisms of λ‐cyhalothrin were competitive, while the other pesticides were noncompetitive.

Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: in vitro inhibition and molecular modeling studies

Abstract Background: Paraoxonase 1 (PON1: EC 3.1.8.1) is a vital antioxidant enzyme against mainly atherosclerosis and many other diseases associated with oxidative stress. Thus, studies related to PON1 have an important place in the pharmacology. In this study, we aimed to evaluate the in vitro inhibition effects of some indazoles on the activity of human PON1. Methods: PON1 was purified from human serum with a specific activity of 5000 U/mg and 13.50% yield by using simple chromatographic methods. Results: The indazoles showed Ki values in a range of 26.0 ± 3.00–111 ± 31.0 μM against hPON1. All these indazoles exhibited competitive inhibition. In addition, molecular docking studies were performed in order to assess the probable binding mechanisms into the active site of hPON1. Molecular modeling studies confirmed our results. Conclusions: Inhibition of PON1 by indazoles supplies a verification to further consideration of limitation dosage of indazole molecule groups as drug.