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Apoptotic and necrotic effects of carboxylated quercetin/polyethylenimine complex on HeLa cells
(Academic Journals, 2011) Ulug, Murat; Turk, Mustafa; Oguztuzun, Serpil; Menemen, Yusuf; Kahraman, Gulten
The effects of quercetin (Q), carboxylated quercetin (CQ) and carboxylated quercetin/polyethylenimine (CQ/PEI) complex on HeLa cell cultures were investigated. Firstly, carboxylated quercetin was acquired through hydroxyl groups of quercetin, using chloroacetic acid. The complex of CQ/PEI was acquired by electron cooperation path over polietilenimine amine groups and quercetin carboxyl groups. CQ and CQ/PEI obtained were characterised by FTIR and H-1-NMR methods. Cytotoxicity was determined by MTT assay. Apoptotic and necrotic indexes were obtained by immunocytochemical staining with the M30 antibodies and double staining and double staining, respectively. It was determined that quercetin caused lower rates of necrosis and apoptosis on HeLa cells by itself, but CQ/PEI complex resulted in high levels. As a result, it was observed that transition of quercetin to HeLa via binding it to polyethylenimine increased its anticarcinogenic effects.
Apoptotic and necrotic effects of plant extracts belonging to the genus Alchemilla L. species on HeLa cells in vitro
(Academic Journals, 2011) Turk, Mustafa; Kaya, Bulent; Menemen, Yusuf; Oguztuzun, Serpil
Apoptotic and necrotic effects of plant extracts belonging to the genus Alchemilla on HeLa cells were investigated. The ratio of viable cells was determined by cell counter. Double staining method for the determination of apoptotic and necrotic index was carried out. The lowest apoptotic effect was found in Alchemilla oriturcica with the ratio of around 14% and the highest apoptotic effect found in Alchemilla trabzonica was 24%. Apoptotic effect was additionally determined by caspase-3 immunostaining. Increasing the concentrations of the extracts, especially in the level of 150 to 200 mu g/mL caused the increase of necrotic effect on cancer cells. Particularly, the effects of A. oriturcica and A. trabzonica extracts with the density of 200 mu g/mL were very high compared to the other species. The flavonoid components were detected in extracts of the species used for this study. The flavonoids identified are orientin (luteolin-8-C-glucoside), hyperoside (quercetin-3-O-galactoside) and isoquercetin (quercetin-3-glucoside) in Alchemilla erythropoda; rutin (quercetin-3-rutinoside), orientin, vitexin (apigenin-8-C-glucoside), hyperoside in Alchemilla ikizdereensis; rutin, hyperoside, isoquercetin (quercetin-3-glucoside) in A. oriturcica, and hyperoside, isoquercetin and quercitrin (quercetin-3-O-rhamnoside) in A. trabzonica.
Biochemical and histopathologic assessment of effects of acitretin on epiphyseal growth plate in rats
(TERMEDIA PUBLISHING HOUSE LTD, 2020) Onder, Sevda; Bilgili, Serap Gunes; Bulut, Gulay; Celik, Huseyin Tugrul; Oguztuzun, Serpil; Onder, Haci; Calka, Omer
Introduction: Acitretin is a commonly used retinoid in dermatology. Although there are generally known side effects, the effects on the epiphyseal plaque and bone metabolism are not clear in the literature. Aim: To histopathologically investigate the effects on the epiphyseal plate and assess variations in bone metabolism caused by acitretin. Material and methods: Three groups were formed with 10 rats in each group. The 1st group (n = 10, 5 male, 5 female) were administered 10 mg/kg/day oral acitretin solution and the 2nd group (n = 10, 5 male, 5 female) were administered 3 mg/kg/day oral acitretin solution. The control group were given normal standard feed and water. Rats were sacrificed at the end of 4 weeks. The proximal tibias were excised and histopathologically and immunohistochemically assessed. Biochemical assessment was also carried out. Results: Staining with haematoxylin-eosin found reductions in the epiphyseal plate in the 1st and 2nd group compared to the control group, though this situation was not statistically significant. Immunohistochemical studies did not encounter Type II collagen in the epiphyseal bone, proliferative zone and hypertrophic zone in the control group, low dose acitretin solution group and high dose acitretin solution group. Type II collagen was not observed in osteoids and osteoblasts. Type I collagen was not observed in the hypertrophic zone and proliferative zone of any group. Conclusions: Our data show that though acitretin caused degeneration of the epiphyseal plate, it did not cause clear thinning and we identified no significant variations in bone metabolism markers.
Chemoresistance in Malignant Intracranial Tumors: Longer Survival with Negative MDR1 Expression
(Turkish Neurosurgical Soc, 2021) Ezgu, Mehmet Can; Kural, Cahit; Simsek, Gulcin Guler; Kaygin, Pinar; Oguztuzun, Serpil; Kirik, Alparslan; Yasar, Soner
AIM: To analyze the Glutathione S-transferase (GST)-P, GST-M, cytochrome p450 (CYP)1-A1, CYP1-B1, and multidrug resistance (MDR)-1 expressions in malignant intracranial tumor (ICT)s, and to elicit their role on patient survival. MATERIAL and METHODS: GST-P, GST-M, CYP1-A1, CYP1-B1, and MDR-1 expressions were analyzed using immunostaining in 149 samples from 141 patients with preoperative ICT diagnosis. The case characteristics were reviewed, and the enzyme expressions were equated based on the age, gender, and tumor type. Then, 77 of 141 patients with malignant ICT and complete medical records postoperative were also investigated in detail for the relationship between the diagnosis, enzyme expression, and overall survival. RESULTS: The average age was 49.44 years, with 83 (58.45%) male patients. Among the 77 malignant ICTs, 38 (49.3%) and 29 were glial tumors and metastases, respectively, with a 13.35-month overall survival. Patients with metastatic tumor have approximately threefold higher GSTP level than those with glial tumors. MDR-1 expression was approximately twofold higher in > 60-year-old patients. No statistically significant association was found between patients' smoking behaviors, alcohol consumption, and overall survival. Only MDR-1 expression was correlated with overall survival. Better overall survival was observed in patients with a negative MDR-1 expression than those with a positive one. CONCLUSION: MDR-1 is an important indicator of survival in malignant intracranial tumor patients. Longer survival is associated with negative MDR-1 expression.
Comparison of the tissue expressions of glutathione S transferase isoenzymes among patients with morphea and healthy controls: A preliminary study
(WILEY, 2020) Uzuncakmak, Tugba Kevser; Koska, Mahmut Can; Ozkanli, Seyma; Kocdogan, Arzu Kaya; Oguztuzun, Serpil; Karadag, Ayse Serap; Akdeniz, Necmettin
Morphea is an inflammatory connective tissue disorder, which is characterized by sclerosis in skin and subcutaneous tissues with a chronic progress. The oxidative stress in pathogenesis of sclerosing diseases was proposed in several studies with conflicting results. To explore the tissue expressions of Glutathione S transferase (GST) isoenzymes in patients with morphea and compare these expressions with healthy controls. Twenty-two morphea patients and 20 sex and age matched healthy controls were enrolled in this study. Four millimeter punch biopsies were performed from the active sclerotic plaques of morphea patients. Tissue samples of control group were obtained from nonlesional normal skin biopsy specimens. The protein expressions of GST isoenzymes were analyzed immunohistochemically. Tissue expressions of GSTP1, GSTT1, and GSTA1 isoenzymes in morphea patients were found to be significantly higher than in control tissues. There was no significant difference in GSTM1 isoenzyme expression between the two groups. The increased tissue expressions of GSTA1, GSTP1, and GSTT1 isoenzymes in morphea may represent the activated GST enzymes in response to excessive free radical formation and may also support the hypothesis of increased oxidative stress in morphea etiopathogenesis.
Comparison of TLR-2, TLR-4, and antimicrobial peptide levels in different lesions of acne vulgaris
(Taylor & Francis Ltd, 2016) Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Kilic, Murat; Zemheri, Ebru; Akdeniz, Necmettin
Context: Recent studies have shown that tolls like receptors (TLRs) and antimicrobial peptides (hBD-1, cathelicidin) play an important role in the pathogenesis of acne vulgaris (AV).Objective: To evaluate and report the expression of TLR-2, TLR-4, hBD-1 and cathelicidin in different regions of skin in AV.Participants: This study was performed in 80 patients with AV and a control group of 20 healthy individuals.Material and methods: Skin biopsies were performed from 20 papular, 20 pustular, 20 comedonal and 20 nodular lesions of patients and 20 healthy volunteers. Expression levels of TLR-2, TLR-4, hBD-1 and cathelicidin in four separate areas (epidermis, dermis, inflammation region and skin appendages) were evaluated by immunohistochemical method. Further, these parameters were compared between different skin lesions.Results: A significant difference was found between the levels of staining of TLR-2, TLR-4 and hBD-1 from the epidermis, inflammation region, dermis and skin appendages (p<0.05). Levels of cathelicidin were different in only the inflammation region (p<0.05). The level of TLR-2 in the epidermis with nodules was lower than the papules and comedones (p<0.05). Levels of TLR-2 in the inflammation and dermis of the cases with papules were significantly higher when compared to pustules (p<0.05). The levels of staining of TLR-4 in the dermis with comedones were significantly lower compared to the cases with papules (p<005). The level of hBD-1 in the epidermis region of comedones was significantly higher compared to nodules (p<0.05). The expression of cathelicidin in the inflammation region of comedones was significantly low (p<0.05).Conclusion: It is thought that TLR-2, TLR-4, hBD-1 and cathelicidin play an important role in the pathogenesis of AV and in the development of different acne types. We think that, better results could be obtained in treatment of AV with different treatment options targeted in regulation of TLR-2, TLR-4, hBD-1 and cathelicidin release.
Cytotoxicity and apoptotic effects of nickel oxide nanoparticles in cultured HeLa cells
(Via Medica, 2010) Ada, Kezban; Turk, Mustafa; Oguztuzun, Serpil; Kilic, Murat; Demirel, Mehmet; Tandogan, Nisa; Latif, Ozturk
The aim of this study was to observe the cytotoxicity and apoptotic effects of nickel oxide nanoparticles on human cervix epithelioid carcinoma cell line (HeLa). Nickel oxide precursors were synthesized by an nickel sulphate-excess urea reaction in boiling aqueous solution. The synthesized NiO nanoparticles (<200 nm) were investigated by X-ray diffraction analysis and transmission electron microscopy techniques. For cytotoxicity experiments, HeLa cells were incubated in 50-500 mu g/mL NiO for 2, 6, 12 and 16 hours. The viable cells were counted with a haemacytometer using light microscopy. The cytotoxicity was observed low in 50-200 mu g/mL concentration for 16 h, but high in 400-500 mu g/mL concentration for 2-6 h. HeLa cells' cytoplasm membrane was lysed and detached from the well surface in 400 mu g/mL concentration NiO nanoparticles. Double staining and M30 immunostaining were performed to quantify the number of apoptotic cells in culture on the basis of apoptotic cell nuclei scores. The apoptotic effect was observed 20% for 16 h incubation.
Describing the Expression Profiles of Glutathione S-Transferase Mu and Tumor Protein 53 in Brain Tumor Tissue
(Erciyes Univ Sch Medicine, 2024) Dirican, Onur; Kaygin, Pinar; Lti, Sezen Yilmaz Saria; Yilmaz, Can; Simsek, Gulcin; Oguztuzun, Serpil; Coban, Tuelay
Objective: This study aims to explore the expression profiles of the glutathione S-transferaseMu (GST-M) isozyme and tumor protein 53 (p53) in both healthy and tumorous brain tissues. The findings are compared with clinical features and lifestyle factors to identify potential associations or correlations. Materials and Methods: We retrospectively analyzed the medical records of 149 patients diagnosed with primary or metastatic intracranial tumors. The expression levels of GST-M and p53 proteins were assessed in healthy and tumorous brain tissues using immunohistochemical staining. We also evaluated the associated clinical features and lifestyle factors. Results: There was a significant difference in the expression levels of GST-M between tumorous and healthy brain tissues, with tumor tissues showing higher expression (p<0.0001). Conversely, robust p53 expression was absent in both normal (97.3%) and tumor (78.5%) tissues. Nevertheless, a significantly higher prevalence of samples with p53 expression was found in the tumor group (p<0.0001). No associations were found between expression levels and clinical features or lifestyle risk factors. Furthermore, GST-M and p53 expression did not impact postoperative survival rates. Conclusion: The findings indicate an elevated expression of GST-M in brain tumor tissues, suggesting a potential role for GST-M in brain tumorigenesis.
The Effect of CYP1A1 and GSTP1 Isozymes on the Occurrence of Aortic Aneurysms
(Georg Thieme Verlag Kg, 2015) Simsek, Erdal; Kilic, Murat; Simsek, Gulcin; Oguztuzun, Serpil; Moran, Busra; Saritas, Ahmet; Ulus, A. Tulga
Background Aortic aneurysms are vascular diseases that are associated with high mortality and morbidity. Cytochrome P450 CYP1A1 and glutathione S-transferase (GSTP1) isozymes were searched and compared with the patients who had experienced aortic surgery due to aortic aneurysm and atherosclerotic patients without aneurysm to find the relation of the oxidative stress with the aneurysms. Materials and Methods Study group consisted of the patients with the diagnosis of aortic aneurysm (group I, n: 12) and control group who were operated for coronary bypass surgery: preoperatively drug users (group II, n: 21) and nonusers (group Ill, n: 15). Paraffin sections (4 pm thick) of aortic biopsy materials were stained with hematoxylin and eosine, CYP1A1 and GSTP1 immunohistochemical markers. The specimens were evaluated using light microscopy at 40- to 400-fold magnification. Results The expressions of CYP1A1 and GSTP1 isozymes were found statistically significantly higher in the patients who have an aortic aneurysm than both the control groups (p < 0.05). There was no significant association between protein expressions, drugs and duration of usage, patient's demographic variables, and smoking (p > 0.05). Conclusions In this pioneering study, CYP1A1 and GSTP1 isozymes are related with the aneurysms. The strategy that prevents the oxidative stress for the patients who had aortic aneurysms could be a valuable choice of searching to effect the aneurysmal progression.
Effects of Different Doses of Systemic Isotretinoin on Eyes: A Histopathological and Immunohistochemical Study in Rats
(Lippincott Williams & Wilkins, 2020) Karadag, Remzi; Karadag, Ayse Serap; Ozlu, Emin; Oguztuzun, Serpil; Simsek, Gulcin Guler; Esmer, Oktay; Bilgili, Serap Gunes
Purpose: To evaluate ocular side effects associated with systemic isotretinoin histopathologically. Methods: In this multicenter study, a total of 15 male and 15 female rats were randomly divided into 3 equal groups according to the oral dose of isotretinoin they were administered: 0 mg/kg/d (group A), 7.5 mg/kg/d (group B), and 15 mg/kg/d (group C). Biopsy specimens were taken from the globe conjunctiva, cornea, and eyelid conjunctiva. Expression levels of human beta-defensin-1, human beta-defensin-2, toll-like receptor (TLR)-2, and TLR-4 were evaluated by immunohistochemical methods. Results: The number of goblet cells in eyelid conjunctiva was significantly lower in group B than that in group A and group C (P = 0.002). The sizes of meibomian gland acini were significantly smaller in group B and group C than those in group A (P < 0.001). Fibrosis of eyelid conjunctiva was significantly higher in group C and group B than that in group A (P = 0.002). The levels of staining of TLR-4 in the cornea with group B were significantly lower compared with group C (P = 0.035). Conclusions: Our study suggests that isotretinoin in the early period affects eyelid conjunctiva and meibomian glands without affecting the globe conjunctiva and cornea. Occurrence of the initial symptoms of isotretinoin on the eyelids, especially on the meibomian glands, suggests that the symptoms of patients occur because of evaporative dry eye.
Evaluation of HBD-1, HBD-2 and LL-37 levels in patients with psoriasis vulgaris after phototherapy
(Mosby-Elsevier, 2016) Uzuncakmak, Tugba Kevser; Karadag, Ayse Serap; Ozkanli, Seyma; Ozlu, Emin; Akdeniz, Necmettin; Oguztuzun, Serpil
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Evaluation of oxidative stress via protein expression of glutathione S-transferase and cytochrome p450 (CYP450) soenzymes in psoriasis vulgaris patients treated with methotrexate
(Taylor & Francis Ltd, 2018) Akbulak, Ozge; Karadag, Ayse Serap; Akdeniz, Necmettin; Ozkanli, Seyma; Ozlu, Emin; Zemheri, Ebru; Oguztuzun, Serpil
Introduction: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes that are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the glutathione S-transferases (GST), which decrease oxidative stress by reducing oxidative products.Aim: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process.Material and methods: This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15mg/week of MTX for minimum 12weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining.Results: GSTK1, GSTM1 and GSTT1 expressions were significantly higher in the psoriasis tissues than in the control tissues (p<0.05; p<0.05; p<0.05, respectively). In the psoriasis patients, GSTO1 expression was similar the control group. CYP1B1 and CYP2E1 expressions were significantly higher in the pre-treatment and post-treatment psoriasis tissues than in the control tissues (p<0.05; p<0.05; p<0.05; p<0.05, respectively).Conclusion: We found a significant increase in the tissue levels of, either expression of GST, or CYP, which has important role in drug metabolism and oxidative stress. MTX treatment resulted in marked clinical improvement, yet we found that MTX did not have any significant effect on these parameters. CYP2E1 is especially the most important enzyme for MTX metabolism since it is the primarily responsible of the toxic metabolism of various drugs. The other experimental studies involving greater number of patients and other different drug are needed to enlighten the role of oxidant and antioxidant systems and the other possible mechanisms for the pathogenesis of psoriasis.
Expression of antimicrobial peptides in recurrent adenotonsillitis
(Walter De Gruyter Gmbh, 2016) Demir, Mehmet Gokhan; Aydin, Sedat; Erdogan, Banu Atalay; Oguztuzun, Serpil; Kilic, Murat; Barisik, Nagehan Ozdemir
Background: Recurrent acute tonsillitis is one of the most frequent otorhinolaryngology clinic referrals, yet its pathogenesis remains poorly understood. Antimicrobial cationic peptides are components of the innate system. They are generally small, highly positively charged peptides with broad spectrum antimicrobial activity which function as the body's "natural antibiotics". Our aim is to investigate the role of antimicrobial cationic peptides in the susceptibility of patients to recurrent acute tonsillitis. Materials and methods: The study is done with 100 children who had a history of recurrent adenotonsillitis as subject group and 100 children with adenotonsillar hypertrophy as control group. Tonsillar and adenoid tissues are dissected into parts as deep and surface epithelium and investigated semiquantitatively with immunohistochemistry. Human beta defensin (hBD) 1-3 and cathelecidin (LL-37) levels are compared with microscopically. Results: Immunohistochemistry revealed a strong expression of hBD-1, hBD-2 and hBD-3 in tonsillar tissue. Quantification of hBD-1, hBD-2 and hBD-3 expressions are shown more in tonsillar tissue than in adenoids. LL-37 is one of the antimicrobial peptides found in human tonsillar tissue and adenoids, that participates in the innate immune system of these tissues. Statistically, hBD-1, hBD-3 and LL-37 expressions were different in recurrent tonsillitis tissue than control (p < 0.05). Moreover hBD-2 expression was different in adenoid tissue than control (p < 0.05). Conclusion: Antimicrobial peptides have key role in adenotonsillar infections and this defense mechanism increases susceptibility to recurrent infections in upper respiratory tract.
Expression of glutathione-S-transferases isoenzymes and p53 in exfoliated human bladder cancer cells
(Elsevier Science Inc, 2011) Oguztuzun, Serpil; Sezgin, Yasemin; Yazici, Sertac; Firat, Pinar; Ozhavzali, Muzeyyen; Ozen, Haluk
Objectives: This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 immunostaining as a marker of malignancy in urinary cytology, and evaluates their potential effect in increasing diagnostic accuracy in a series of urine cytologic samples. They are also correlated with cytopathology diagnosis and histopathologic diagnosis. Materials and methods: In this study, the slides from 124 bladder carcinoma patients prepared by the cytocentrifugation method were observed. The cytomorphologic properties of these cancer cells were determined. Moreover, the immunocytochemical distributions of GST alpha (GSTA), pi (GSTP), mu (GSTM4), theta (GSTT1) isoenzymes and p53 protein were studied for the patients. Results: The urothelial cancer cells had small cytoplasm and rough nuclear membrane. The chromatin granules were heterogeneously distributed in each malignant cell's nucleus. There was a pleomorphism of the malignant cells' nuclei. According to immunocytopathologic observations, the urothelial cancer cells had stronger staining intensity than the benign cells had in 48% of cases for GSTA, 46% of cases for GSTP, 38% of cases for GSTM4, and 42% of cases for GSTT1. For all papillary cases, the malignant cells were stained negative, while the benign cells were positive. For 83% of patients, the malignant cells were stained positive for p53. There was a significant difference in GSTA (P = 0.006), GSTT1 (P = 0.004), GSTP (P = 0.000) and p53 (P = 0.000) expressions for benign cells whereas, a non-statistical difference in the malignant cells for GSTA, GSTT1, GSTP, GSTM4, and p53 expressions (P > 0.05). Conclusions: GST isoenzymes and p53 immunostaining were not found to be markers of malignancy in urinary cytology. (C) 2011 Elsevier Inc. All rights reserved.
The expression of GST and CYP isoenzymes in thyroid nodular hyperplasia and papillary thyroid cancer tissue: Correlation with clinical parameters
(Entomology & Applied Science Research Letters-Easletters, 2016) Oguztuzun, Serpil; Ergn, Duygu; Kilic, Murat; Bozer, Busra; Simsek, Gulcin Guler; Bulus, Hakan
This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase (GST) pi(P), mu(M), theta(T), omega(O) and kappa(K) cytochrome P450 (CYP) A1, B1 and 2E1 isoenzymes in thyroid nodular hyperplasia (NH) and papillary thyroid cancer (PTC) tissues. For immunohistochemical studies, tissues from 18 patients with thyroid nodular hyperplasia, 28 patients with papillary thyroid cancer at the Kecioren Training and Research Hospital, Ankara, Turkey, were used. Relationships between GST and CYP isoenzyme expressions in NH and PTC tissues were examined by the Mann-Whitney U test, and clinicopathological data were examined by the Pearson Correlation Test and Regression Analysis. When the NH and PTC tissues from these cases were compared with respect to their staining intensity, GSTP1, GSTO1, GSTK1, CYP1A1, CYP2E1 expressions in PTC cells were significantly higher than those in NH epithelial cells (p< 0.05). There were no statistically significant differences in the CYP1B1, GSTT1 and GSTM1 expressions between benign and tumor epithelium (p> 0.05). There were significant association between GSTO1, GSTK1 expressions and sT3 levels in PTC (p< 0.05) and CYP1B1 expression in NH. There was a significant association between GSTO1 expression and smoking status in NH ( p< 0.05). There was no statistical relationship between the GSTM1, GSTT1, GSTP1, GSTO1, GSTK1, CYP1A1, CYP1B1, CYP2E1 isoenzyme expressions and the clinicopathological data (age, TSH, sT4 levels, tumor stage) ( p> 0.05). GSTP1, GSTO1, GSTK1, CYP1A1 and CYP2E1 isoenzymes may have roles in the carcinogenesis of the papillary thyroid cancer.
The expression of GST isoenzymes and p53 in non-small cell lung cancer
(Via Medica, 2010) Oguztuzun, Serpil; Aydin, Mehtap; Demirag, Funda; Yazici, Ulku; Ozhavzali, Muzeyyen; Kilic, Murat; Iscan, Mesude
This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase alpha, pi, mu, theta and p53 in non-small cell lung carcinoma and normal lung tissue from 50 patients. The relationships between expressions of the Glutathione-S-transferase isoenzymes and some clinicopathological features were also examined. Expression of glutathione-S-transferase pi, mu, alpha, theta and p53 was assessed by immunohistochemistry for primary lung carcinomas of 50 patients from the Sanitarium Education and Research Hospital, Ankara lung cancer collection. The relationships between expression of the glutathione-S-transferase isoenzymes, p53 in normal and tumor tissue by Student T test and the clinicopathological data were also examined by Spearman Rank tests. When the normal and tumor tissue of these cases were compared according to their staining intensity and percentage of positive staining, glutathione-S-transferase alpha, pi, mu, theta expressions in tumor cells was significantly higher than normal cells (p<0.05). There was no significant difference in the expression of p53 between normal and tumor cells (p>0.05). When the immunohistochemical results of glutathione-S-transferase isoenzymes and p53 were correlated with the clinical parameters, there were no significant associations between glutathione-S-transferases and p53 expressions and tumor stage, tumor grade and smoking status (p>0.05).
The expression of GST isoenzymes in acinar adenocarcinoma, intraepithelial neoplasia, and benign prostate tissue: correlation of clinical parameters with GST isoenzymes
(Tubitak Scientific & Technical Research Council Turkey, 2012) Simsek, Gulcin; Oguztuzun, Serpil; Guresci, Servet; Kilic, Murat; Bozkurt, Omer Faruk; Unsal, Ali
This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase (GST) alpha, pi, mu, and theta in prostatic acinar adenocarcinoma (PCA), prostatic intraepithelial neoplasia (PIN), and benign prostatic tissues from 19 patients. Relationships between GST isoenzyme expression in benign, PIN, and PCA tissue were examined by the Wilcoxon signed-rank test and clinicopathological data were examined by the Spearman correlation rank test. When the benign, PIN, and PCA tissues from these cases were compared according to their staining intensity, GST alpha, pi, mu, and theta expressions in tumor cells were significantly lower than in benign epithelial cells (P<0.05). The GST alpha class displayed the lowest level of expression in PIN and PCA. Expression of GST pi was lower in PCA tissue than in PIN and benign epithelial tissue (P<0.05). We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST isoenzymes and other detoxifying and antimutagenesis agents. This study confirms the down-regulation of GST isoenzymes in PCA of the prostate and shows that the loss of GST isoenzyme expression is a phenotype associated with malignant transformation. There was no statistical relationship between GST isoenzyme expression and the clinicopathological data (age, Gleason score, and total serum prostate-specific antigen levels) (P>0.05).
Expressions of CYP and GST Isoenzymes in Human Gastric Tumor and Non-Tumor Tissues
(Akad Doktorlar Yayinevi, 2018) Simsek, Gulcin G.; Oguztuzun, Serpil; Bozer, Busra; Kilic, Murat; Kocdogan, Arzu K.; Kaygin, Pinar; Bulus, Hakan
In this study we investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1 and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 isoenzymes in gastric tumor and surrounding tumor free (normal) gastric tissues from 40 patients. For immunohistochemical studies, tissues were obtained from 40 patients with gastric adenocarcinoma. Tumor and non-tumoral control tissues of patients were compared according to their staining intensity. Relationships between CYP and GST isoenzyme expressions in adenocarcinoma tissues were examined by the Mann Whitney-U test, and the clinicopathological data were examined by the Spearman's Rank Correlation test. CYP1B1, GSTT1, GSTO1 and GSTK1 expressions in gastric cancer cells were significantly higher than those in gastric normal epithelial cells (p < 0.05). However, CYP1A1, CYP2E1 and GSTP1 expressions were not significantly higher in tumor epithelium than those in normal epithelium in human gastric adenocancer (p < 0.05). Among the studied CYPs and GSTs, there was not statistically significant association between the studied isoenzyme expressions and age, gender and tumor grade ( p > 0.05). In patients with gastric adenocarcinoma, CYP1B1, GSTO1, GSTT1, and GSTK1 protein expressions are higher in tumor than normal gastric tissues.
Expressions of glutathione S-transferase alpha, mu, pi, and theta in the skin samples of patients with acne rosacea
(WILEY, 2020) Takci, Zennure; Bilgili, Serap Gunes; Kilic, Murat; Oguztuzun, Serpil; Bozer, Busra; Simsek, Gulcin Guler; Akbayrak, Atiye
Background Data point to the importance of oxidative stress in rosacea. Glutathione S-transferases (GSTs) have substantial roles in a wide variety of oxidative stress-related conditions. Aim To evaluate the immunohistochemical staining characteristics of GST alpha (GSTA), mu (GSTM), pi (GSTP), and theta (GSTT) in patients with rosacea. Patients/Methods The study included 23 women and 7 men with rosacea (mean +/- SD age 49 +/- 11 year) and 15 healthy control subjects (10 women, 5 men; mean +/- SD age 47.86 +/- 10.88 year). For each patient, the average disease duration, disease subtype, ocular involvement, and severity score were recorded. A 3-mm punch biopsy was taken from the facial skin of each patient and control. Expression of GST isoenzymes was analyzed immunohistochemically. Results Expressions of GSTM1, GSTP1, and GSTT1 were significantly elevated in patients with rosacea compared to those in the control group (P = .0001,P = .0002,P < .0001, respectively). In the rosacea group, GSTT1 expression was significantly stronger than GSTP1 and GSTA1 expressions (P = .019,P < .0001, respectively). There were no significant associations between expressions of GST isoenzymes and gender, age, average duration of illness, disease subtype, ocular involvement, or severity score in the patient group (allP > .05). Conclusions In rosacea, the significant increase of GSTT1, GSTP1, and GSTM1 expressions might result from activation of GST as an outcome of extreme free radical generation from triggered neutrophils or ultraviolet vulnerability. These findings support the relevance of oxidant stress in the pathogenesis of rosacea.
Glutathione S-transferase enzyme activity and protein expression in patients with recurrent tonsillitis and idiopathic tonsillar hypertrophy
(Palacky Univ, Medical Fac, 2019) Aydin, Sedat; Demir, Mehmet Gokhan; Oguztuzun, Serpil; Kilic, Murat; Yilmaz, Can; Dirican, Onur
Objectives. The palatine tonsil is a significant part of the secondary immune system. Tonsillitis and idiopathic tonsillar hypertrophy (ITH) are the most common pathologies of this component. Although there are studies on their pathogenesis, there is insufficient study of the role of antioxidant agents. Glutathione S-transferase (GST) isozymes contribute to the antioxidation reactions in the tissue via the glutathione pathway. The purpose in this study was to reveal the levels of the GST enzyme activity and protein expression of GSTP1 and GSTA1 isozymes in patients with tonsillitis and tonsil hypertrophy, and to investigate their role in the pathogenesis of these diseases. Materials and Methods. Sixteen patients with recurrent tonsillitis and 5 patients with ITH and were included in the study. Cytosolic extracts were prepared from post-tonsillectomy tissues of both patient groups and GST enzyme activities were measured. Results. The expression of GSTP1 was found to be significantly higher than GSTA1 in tissue samples of patients with ITH and recurrent tonsillitis (P<0.001). Increased GST activity and GSTP1 isozyme expression were shown in patients with recurrent tonsillitis compared to the idiopathic tonsillar hypertrophy study group.There was a positive correlation between the expressions of GSTP1 (P=0.040; r=0.47). Conclusion. Increased GST activity and GSTP1 isozymes were demonstrated histologically in the pathogenesis of ITH and recurrent tonsillitis. We believe that the data of changes in antioxidant capacity, obtained from studies with more extensive and larger samples, would support our findings.

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