Gul Ozhan | Istanbul University (original) (raw)

Papers by Gul Ozhan

PubMed, 2018

In the present work we carried out a phytochemical and biological investigation on three endemic ... more In the present work we carried out a phytochemical and biological investigation on three endemic Hypericum species, i.e.Hypericum thymbrifolium (H. thymbrifolium), Hypericum spectabile (H. spectabile) and Hypericum pseudolaeve (H. pseudolaeve) from Anatolia in order to discover new sources of natural compounds for the treatment of inflammatory and neurodegenerative disorders. HPLC-DAD analysis indicated that two naphthodianthrones (pseudohypericin and hypericin) together with chlorogenic acid, rutin, hyperoside, isoquercitrin, kaempferol, quercitrin, quercetin, amentoflavone, and hyperforin are the main compounds present in the methanol extracts. After chemical characterization, all extracts were in-vitro biologically assayed for antioxidant potential by lipid peroxidation inhibitory activity, DPPH, FRAP assays, and superoxide radical scavenging activity, for AChE inhibitory activity by Ellman's method, for COX inhibitory activity by using enzyme immunoassay (EIA) kit, for cytotoxic activity on HeLa and NRK-52E cell lines by MTT assay. The superoxide radical scavenging activity and lipid peroxidation inhibitory activity of H. spectabile (EC50 = 0.430 mg/mL) were more remarkable than that of H. thymbrifolium and H. pseudolaeve. The extracts showed moderate inhibitory activity on AChE (from 49.37% to 63.41%). The best inhibitory activity against COX-1 (71.77% and 77.04%, respectively) and COX-2 ( 64.14% and 72.23%, respectively) were shown by H. thymbrifolium and H. spectabile, which may be due to their richest chlorogenic acid content (0.29576% and 0.23567%, respectively). Cytotoxicity screening results showed that the extracts did not demonstrate significant cytotoxic activity. It was concluded that the most promising extract with antioxidant, anti-inflammatory, and AChE inhibition potential is H. spectabile.

Industrial Crops and Products, Oct 1, 2013

ABSTRACT The chemical composition of methanolic extract of Hypericum pamphylicum (HPM) was analyz... more ABSTRACT The chemical composition of methanolic extract of Hypericum pamphylicum (HPM) was analyzed by usinghigh performance liquid chromatography–diode array detector (HPLC-DAD). The plant contained hyper-icin (0.00002 ± 0.000001%), hyperforin (trace), chlorogenic acid (5.58 ± 1.59%), hyperoside (0.46 ± 0.05%),isoquercitrin (0.134 ± 0.02%) and quercetin (0.087 ± 0.008%). The antioxidant activity of HPM was eval-uated by using several antioxidant tests. HPM exhibits inhibitory capacity against phosphatidylcholineliposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals andact as reductants. The cytotoxic activity of HPM was also determined by using MTT cell viability assay onHeLa and NRK-52E cell lines. HPM demonstrated no cytotoxicity against HeLa and NRK-52E cell lines withIC50values of 1.89 mg/ml and 1.05 mg/ml, respectively. The different crude extracts of H. pamphylicumwere analyzed using a microdilution assay for antimicrobial activity against several microorganisms. Themost active extract was HPM which showed activity against Staphylococcus aureus. It is observed thatnearly all extracts showed activity against Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumo-niae, Pseudomonas aeruginosa, Salmonella thypi, Shigella flexneri, Proteus mirabilis and Candida albicans.

İstanbul Journal of Pharmacy

Background and Aims: Nickel oxide nanoparticles (NiO-NPs) are one of the most used nanoparticles,... more Background and Aims: Nickel oxide nanoparticles (NiO-NPs) are one of the most used nanoparticles, especially as photosensitizers. Although some studies evaluate their toxicity in the liver, the information about their toxicity at the cellular and molecular levels is still controversial. In the present study, it was aimed to investigate the in vitro toxic potentials of NiO-NPs (average size 15.0 nm) in the liver (HepG2) cell line. Methods: NiO-NPs were characterized by Transmission Electron Microscopy (TEM), the cellular uptake of NPs and the morphologic changes were evaluated by TEM and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), the cytotoxicity was evaluated by MTT and neutral red uptake (NRU) tests, comet assay was used for genotoxicity, Annexin V-FITC/propidium iodide (PI) apoptosis detection kit was used for apoptosis/ necrosis evaluation and Enzyme-Linked Immune Sorbent Assays (ELISA) kits were used for the potential of oxidative damage. Results: Our results showed that cellular uptake of NiO-NPs led to morphological changes in the cells, and caused cell death (IC50 was 146.7 µg/mL by MTT) mainly by apoptosis. Genotoxicity and oxidative damage were observed to be in a dosedependent manner. Conclusion: Results confirm previous data and draw attention to the toxic effects of NiO-NPs; further in vivo and in vitro studies need to be done to clarify the safety or toxicity of NiO-NPs.

Turkish Journal of Medical Sciences

Introduction Since the 10th century, diabetes has been associated with sexual dysfunction. Avicen... more Introduction Since the 10th century, diabetes has been associated with sexual dysfunction. Avicenna described this a "collapse of sexual function" as a special complication of diabetes. Diabetes causes significant changes on the various structures and mechanisms of the male reproductive system through endocrine disorders, neuropathy and increased oxidative stress. Diabetic infertility has been shown to affect 15% of couples, and diabetes is becoming an increasingly complicated health problem worldwide. It is important to control blood glucose levels in diabetes patients because damage is caused by glucose toxicity due to hyperglycaemia [1,2]. DAPA is an insulin-independent antidiabetic drug that acts as a SGLT2 inhibitor and aims to control Background/aim: Dapagliflozin (DAPA), sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an insulin-independent antidiabetic drug used to control hyperglycaemia by promoting glucose excretion from the kidney. Its adverse effects include orthostatic hypotension, dehydration and urinary tract and genital infections caused by glycosuria. DAPA is subjected to constant additional monitoring, as drugrelated adverse reactions are frequently updated in line with the results of case studies, clinical trials and in vivo studies. Some antidiabetic drugs have shown potential harmful effects on the male reproductive system; however, the effects of DAPA have not been sufficiently studied in this capacity. Aiming to fill this gap in the literature, the present work investigates the toxic effects of DAPA on the male reproductive system. Materials and methods: Diabetes was induced using streptozotocin (STZ) in adult male Sprague-Dawley (SD) rats. DAPA (10 mg/kg) was administered by gavage to the diabetic rats over 28 days, after which the animals were sacrificed. The biochemical, morphological and histological examinations were performed on testicle, sperm and plasma samples. Results: As a result of this study, we observed reproductive system damage in the form of induction of apoptosis in the seminiferous tubules, changes in testis and sperm parameters and oxidative damage, alongside the development of diabetes in test animals. With the exception of sperm morphological damage, the changes observed in diabetic animals treated with DAPA were similar to those of the control group. Improvements were observed in histological, hormonal and proliferative parameters in the DAPA group compared to the DC group. Conclusion: Even if DAPA is found to have antioxidant effects, it may raise abnormal sperm counts through a mechanism completely independent of these effects and thus may not have a significant toxic effect on the male reproductive system.

Records of Natural Products

In addition to the antiflatulent, emollient, antifungal, antihemorrhoidal, antioxidant, anthelmin... more In addition to the antiflatulent, emollient, antifungal, antihemorrhoidal, antioxidant, anthelmintic effects, Prangos species have been used to stop bleeding and for the treatment of wounds and scars in central Asia and Turkey. In the present study, the compounds were isolated using chromatographic methods, and their structures were identified by 1H NMR and direct comparison with the reference compounds where available. Fifteen known coumarins were isolated from the dichloromethane extract as osthol, murraol, auraptenol, peroxyauraptenol, 4'-senecioiloxyosthol, meranzin hydrate, scopoletin, umbelliferone, isoimperatorin, oxypeucedanin, oxypeucedanin hydrate, oxypeucedanin methanolate, gosferol, psoralen, and marmesin. The cytotoxic activities of all isolated compounds from dichloromethane extract of P. turcica roots were evaluated using MTT assay on human adenocarcinoma (prostate PC-3) cells. 4'-senecioiloxyosthol, oxypeucedanin methanolate, gosferol, psoralen, peroxyaurapte...

Journal of Health and Pollution

Background. Perfluorooctanoic acid (PFOA) is used in different industrial and commercial products... more Background. Perfluorooctanoic acid (PFOA) is used in different industrial and commercial products. Research shows the presence of PFOA in home dusts, tap and surface water, and in biological samples. The International Agency for Research on Cancer (IARC) has classified PFOA as a possible carcinogen for humans. The liver is thought to be a target organ of PFOA accumulation and toxicity. Objective. Some studies have found toxic effects on the liver and related mechanisms; however, more studies are needed to better understand PFOA - induced hepatotoxicity. Methods. In the present study, a human hepatocarcinoma cell line was exposed to PFOA for 24 hours and cell viability, apoptosis, the oxidative system and immune response were evaluated. Results. While apoptosis was the main cell death pathway at low concentration (86.5%), the necrotic cell fraction increased with higher concentrations (46.7%). Significant changes in the reactive oxygen species (5.3-folds) glutathione (GSH) (1.7-folds...

Toxicology Mechanisms and Methods

International Journal of Pharmacy and Pharmaceutical Sciences, 2016

Objective: The aim of this study, we based on protective and antioxidant efficiency of Hypericum ... more Objective: The aim of this study, we based on protective and antioxidant efficiency of Hypericum perforatum that shows a wide range of beneficial effect in vitro and in vivo . Methods: The in vitro antioxidant activity of the extract was assessed by using several antioxidant tests. The cytotoxic activity of Hypericum perforatum was also determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide viability assay on ordinary used cell lines. In vivo experiments in Swiss mice were determined by performing behavioral, memory tests and histological study. According to tests results, H. perforatum may be relevant to the treatment of cognitive disorders. Results: The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the 2, 2-diphenyl-1-picrylhydrazyl, Anti-lactoperoxidase and superoxide dismutases; this antioxidant activity was confirmed in vivo after the non-toxic results by ...

World Academy of Science, Engineering and Technology, International Journal of Pharmacological and Pharmaceutical Sciences, 2016

Toxicology Letters, 2016

Copper (II) oxide nanoparticles (CuO-NPs) are widely used in industry, cosmetics and medicine. Pe... more Copper (II) oxide nanoparticles (CuO-NPs) are widely used in industry, cosmetics and medicine. People have increasingly been exposed to these active materials. Several studies indicate that CuO-NPs could be taken up by different organs and cause toxicities. However, there is still a lack of data on the toxicological effects of CuO-NPs in neuronal system. In the present study, the toxic potentials of CuO-NPs were investigated in human SH-SY5Y neuroblastoma cells. After assessment of their cellular uptake potential, cytotoxicity by MTT and neutral red uptake (NRU) and genotoxicity by comet assay were evaluated. Enzyme-Linked Immune Sorbent Assays (ELISA) determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), protein carbonyl (PC), and glutathione (GSH) levels for oxidative damage, and Annexin V-FITC with propidium iodide (PI) for apoptosis were used. In conclusion, CuO-NPs were found to accumulate in the cells and induced significant cytotoxic and genotoxic, and oxidative and apoptotic effects. CuO-NPs are hypothesized to dangerously affect human health, especially neuronal system.

Drug Delivery and Translational Research, 2021

Acne is a chronic dermatological disease of pilosebaceous units existing in the form of hair foll... more Acne is a chronic dermatological disease of pilosebaceous units existing in the form of hair follicles (HFs) and accompanying sebaceous glands. In topical acne treatment, localisation of drug substance at the target site, in pilosebaceous units, especially in HFs is essential. The aims of this study were to develop and optimise adapalene (ADA)-loaded PAMAM dendrimer-based nanocarriers for topical acne treatment and to prepare gel formulations of the selected nanocarriers and to characterise their rheological properties and spreadability. ADA accumulation in HFs and in the skin from PAMAM dendrimers’ aqueous colloidal formulations and their gel formulations were quantitatively determined using punch biopsy technique. Follicular targeting efficiency from PAMAM dendrimers and their gel formulation was compared with the commercial gel product, Differin ® Gel. The localisation of fluorescently labelled PAMAM dendrimers was visualised using a confocal microscope, which confirmed a successful delivery of the carrier system to the HFs. It was also quantified that PAMAM dendrimers improved follicular localisation and skin deposition of ADA. PAMAM dendrimers’ gel formulation including lower ADA doses compared with the commercial product exhibited efficient performance in terms of drug accumulation in HFs. In vitro cell viability studies showed the relative safety of G2-PAMAM dendrimers which could be considered to possibly be well tolerated by the skin. Overall, PAMAM dendrimers’ potential to selectively target drugs to the site of action, reduce dose administrated, therefore minimise side effects and provide efficiency in topical treatment of dermatological diseases such as acne was shown. Graphical abstract

İstanbul Journal of Pharmacy, 2020

Background and Aims: Occurence of the mycotoxin citrinin could increase during Monascus purpureus... more Background and Aims: Occurence of the mycotoxin citrinin could increase during Monascus purpureus fermentation in red yeast rice resulting in contamination of meat products when the red yeast rice is used as food additive. The aim of this study was to investigate extraction of citrinin from meat products by different extraction methods including LLE, QuEChERS and IAC methods. Methods: Because of high sensitivity IAC method was selected for the extraction of citrinin in 33 meat products (salami, sausage and minced meat), then citrinin was analysed by HPLC-FLD. Results: IAC method was linear in the range of 0.25-100 ng/g (r 2 ≥0.999) in meat products. Citrinin was found at 0.28 to 1.79 ng/g in 6 of the 19 samples (36.84%); and in one sausage sample contained citrinin at LOD level. However, citrinin was not detected in the salami and minced meat samples. Conclusion: Our results indicated that citrinin in meat products could be an important health concern. Since no limits were set in food products, regulations should be developed concerning the presence of citrinin in other products as well as meat products, in Turkey.

Global Medical Genetics, 2020

Paraoxonase 1 (PON1) enzyme plays a major role in antioxidant defense and protects the cells agai... more Paraoxonase 1 (PON1) enzyme plays a major role in antioxidant defense and protects the cells against reactive species. The most common PON1 Q192R and L55M polymorphisms are responsible for a wide variation of PON1 activity, which showed an up to 13-fold interindividual variation among the same genotype. PON1 genotypes were evaluated with the development of pancreatitis, colorectal cancer, and hypothyroidism in a hospital-based, case-control study. Individuals with rs662 G allele had a two-fold risk of developing hypothyroidism. A weak association was found between rs854560 T allele and pancreatitis. The results were preliminary. Further studies with a larger number and detailed biochemical parameters are needed.

Advanced Pharmaceutical Bulletin, 2020

Purpose: The wide application of cupric oxide nanoparticles (copper (II) oxide, CuO-NPs) in vario... more Purpose: The wide application of cupric oxide nanoparticles (copper (II) oxide, CuO-NPs) in various fields has increased exposure to the kind of active nanomaterials, which can cause negative effects on human and environment health. Although CuO-NPs were reported to be harmful to human, there is still a lack information related to their toxic potentials. In the present study, the toxic potentials of CuO-NPs were evaluated in the liver (HepG2 hepatocarcinoma) and intestine (Caco-2 colorectal adenocarcinoma) cells. Methods: After the characterization of particles, cellular uptake and morphological changes were determined. The potential of cytotoxic, genotoxic, oxidative and apoptotic damage was investigated with several in vitro assays. Results: The average size of the nanoparticles was 34.9 nm, about 2%-5% of the exposure dose was detected in the cells and mainly accumulated in different organelles, causing oxidative stress, cell damages, and death. The IC50 values were 10.90 and 10....

Toxicology and Industrial Health, 2019

Acetamiprid, a selective agonist of type-2 nicotinic acetylcholine receptors, is one of the most ... more Acetamiprid, a selective agonist of type-2 nicotinic acetylcholine receptors, is one of the most widely used neonicotinoids. The hepato- and nephrotoxic potential of acetamiprid has not been clarified although it is known to be toxic to other several organ systems, including the nervous, respiratory and immune systems. The present study aimed to investigate acetamiprid liver and kidney toxicity in male rats after a 90-day subchronic exposure to 12.5, 25 and 35 mg/kg. The biochemical and oxidative damage parameters were determined in the plasma and tissue samples as well as histopathological evaluation in the liver and kidney tissues. Acetamiprid caused oxidative damage and affected the liver, denoted by injury markers including the levels of cholesterol, and alanine aminotransferase and aspartate aminotransferase enzymes. There was also a decrease in plasma urea, uric acid and creatinine levels, all of which might result from liver injury. Additionally, acetamiprid was more toxic to...

Saudi Pharmaceutical Journal, 2019

Objectives: Type 2 diabetes (T2DM) is one of the most serious challenges of the 21th century with... more Objectives: Type 2 diabetes (T2DM) is one of the most serious challenges of the 21th century with lifethreatening complications and excessive health care costs. In diabetic patients, the main goal in T2DM treatment is the regulation of both blood glucose and lipid levels. For that, Gliclazide (GLZ), an oral antidiabetic, and Atorvastatin (ATV), a lipid lowering agent, are widely used drugs as combination. Diabetes has been reported severe impacts on male reproductive system; however, data obtained about ATV and GLZ treatment alone or in combination are conflicted or insufficient. Herein the effects of ATV and GLZ on male reproductive system in type 2 diabetic male rats have been investigated in the present study. Methods: T2DM was induced by high-fat diet and single injection of streptozotocin (STZ) (35 mg/kg) in young adult male Sprague-Dawley rats. The diabetic rats were given ATV (10 mg/kg), GLZ (10 mg/kg) and ATV/GLZ (1:1, 10 mg/kg) combination by oral gavage for 28 days. The hormone levels were determined in the cardiac blood samples; and the histopathological and ultrastructural analyses were conducted in the testicular tissues and epididymal sperms. Results: It was observed that diabetes had severe effects on testicular tissue and spermatogenesis. ATV treatment did not affect sperm count and testes structure (p > 0.05), however ameliorated sperm morphology (p < 0.05). GLZ treatment increased sperm count, and improved sperm morphology, testes structure and spermatogenesis (p < 0.05). ATV/GLZ combination treatment enhanced sperm morphology and improved testicular structure (p < 0.05) while did not affect sperm count (p > 0.05). Conclusion: GLZ treatment regenerated testicular damage and sperm parameters whether alone or in combination with ATV in diabetic rats without affecting hypothalamic-pituitary-gonadal axis.

Marmara Pharmaceutical Journal, 2017

Cobalt oxide (Co 3 O 4) nanoparticles have been extensively used in various industrial and medica... more Cobalt oxide (Co 3 O 4) nanoparticles have been extensively used in various industrial and medical applications due to their special optical, magnetic, and electrical activity features. However, there is a lack of information about their toxicity and adverse effects on human health, especially concerning the kidney, which is considered to be a secondary target organ. We investigated the toxic potentials of Co 3 O 4 nanoparticles on NRK-52E kidney epithelial cells by in vitro assays. Co 3 O 4 nanoparticles were taken up by the kidney cells, and caused a decrease in cell viability, by significantly inducing apoptosis/ necrosis at 100 µg/mL. However, no significant DNA damage was observed. Co 3 O 4 nanoparticles induced cellular toxicity in kidney cells. These results should raise concern about the safety of Co 3 O 4 nanoparticles in their various applications. Further studies are needed to elucidate their toxic mechanism.

Turkish Journal of Pharmaceutical Sciences, 2017

Amaç: Sert manyetik kobalt ferrit nanopartiküllerinin (CoFe 2 O 4-NP) dikkate değer özellikleri v... more Amaç: Sert manyetik kobalt ferrit nanopartiküllerinin (CoFe 2 O 4-NP) dikkate değer özellikleri ve fizikokimyasal kararlılıkları farklı endüstri ve tıp alanlarında çeşitli uygulamalarda kullanılmalarına yol açmaktadır. CoFe 2 O 4-NP'lerin bazı toksik etkilere neden olduğu bildirilmiş olsa da böbrek üzerindeki etkileri hakkında ciddi bilgi eksikliği vardır. Bu çalışmada, CoFe 2 O 4-NPs'lerinin NRK-52E böbrek hücreleri üzerine toksik etki potansiyellerinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: Partikül karakterizasyonu ve hücresel alım transmisyon elektron mikroskopu, dinamik ışık saçılma tekniği ve indüktif eşleştirilmiş plazma-kütle spektrometrisi ile gerçekleştirildi. Sonra, sitotoksisite MTT ve nötral kırmızı alım testi, genotoksisite comet tekniği ve apoptotik potansiyel propidyum iyodürlü Annexin V-FITC apoptoz tayini ile değerlendirildi. Bulgular: CoFe 2 O 4-NP'lere (39±17 nm) 100-1000 μg/mL arasında değişen konsantrasyonlarda 24 saat süre ile maruz bırakılan böbrek hücrelerinde hücre canlılığının etkilenmediği, ancak ≤100 μg/mL'de önemli ölçüde DNA hasarı meydana geldiği gözlenmiştir. Maruz kalan hücrelerde apoptotik veya nekrotik etki gözlenmedi. Sonuç: Elde edilen sonuçlara göre, CoFe 2 O 4-NP'ler çeşitli uygulamalarda güvenli kullanımı vaat etmektedir. Bununla birlikte, etki mekanizmalarının tam olarak anlaşılabilmesi için in vivo çalışmalara ihtiyaç vardır. Anahtar kelimeler: DNA hasarı, hücre ölümü, apoptoz, kobalt ferrit nanopartikülü Objectives: The remarkable properties of hard magnetic cobalt ferrite nanoparticles (CoFe 2 O 4-NPs) and their physicochemical stability lead to various applications in different industrial and medical fields. Although CoFe 2 O 4-NPs have been reported to cause toxic effects, there is a serious lack of information concerning their effects on the kidneys. In this study, it was aimed to investigate the toxic effects of CoFe 2 O 4-NPs on NRK-52E kidney cells. Materials and Methods: The particle characterisation and cellular uptake were determined using transmission electron microscopy, dynamic light scattering and inductively coupled plasma-mass spectrometry. Then, the cytotoxicity was evaluated by MTT and neutral red uptake assays, the genotoxicity by comet assay, and the apoptotic potentials by Annexin V-FITC apoptosis detection assay with propidium iodide. Results: After 24 h exposure to CoFe 2 O 4-NPs (39±17 nm), it was observed they did not affect the cell viability at concentration ranging from 100 to 1000 μg/mL, but significantly induced DNA damage at concentration ≤100 μg/mL. No apoptotic or necrotic effect was observed in the exposed cells. Conclusion: According to the results obtained, CoFe 2 O 4-NPs are promising for safe use in various applications. However, further in vivo studies are needed to fully understand their mechanisms of action.