Zuhal Uçkun Şahinoğulları Zuhal Uçkun Şahinoğulları ECZACILIK FAKÜLTESİ ECZACILIK MESLEK BİLİMLERİ BÖLÜMÜ FARMASÖTİK TOKSİKOLOJİ ANABİLİM DALI
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The Evaluation of Genetic Profiles of UGT1A4 and UGT1A6 in the Turkish Population
Türk Popülasyonunda UGT1A4 ve UGT1A6 Genetik Profillerinin Değerlendirilmesi

UÇKUN ŞAHİNOĞULLARI, ZUHAL

Aim: Uridine diphosphate glucuronosyltransferases (UGTs) are a superfamily of conjugation phase II enzymes and is responsible for catalyzing the glucuronidation of many endobiotic or xenobiotic substrates. The present study aimed to determine allele and genotype frequencies of UGT1A4 c.142T>G, UGT1A6 c.541A>G and UGT1A6 c.19T>G polymorphisms in the healthy Turkish population and also to compare them with different population data. Material and Method: UGT1A4 c.142T>G, UGT1A6 c.541A>G and c.19T>G polymorphisms were determined in DNA samples of 114 healthy Turkish volunteers using polymerase chain reaction and restriction fragment length polymorphism methods. Results: The frequencies of variant alleles were 12.7% for UGT1A4 c.142T>G, 39.9% for UGT1A6 c.541A>G and 44.7% for UGT1A6 c.19T>G. The frequencies of the UGT1A4 and UGT1A6 variant alleles determined were observed to be similar to those of the majority of European populations. However, the UGT1A6 frequencies in the Turkish population differed significantly from those reported specifically for the Thai and East Asian populations. Conclusion: This study introduces the frequencies of UGT1A4 and UGT1A6 polymorphisms in the Turkish population. As a result of our literature reviews, this study is the first report...

Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats

Güzel, Sevda | Uçkun, Zuhal | Canacankatan, Necmiye | Antmen, Ş. Efsun | Kibar, Deniz | Coşkun Yılmaz, Banu

Silymarin (SLY), a flavonoid complex isolated from the seeds of Silybum marianum (Asteraceae), has antioxidant, anti-apoptotic, anti-inflammatory, and anti-lipid peroxidative effects. Vancomycin (VA), used for treating serious infections, has been associated with nephrotoxicity, which limits its use. Therefore, this study aimed to investigate the potential renoprotective effects of SLY on VA-induced nephrotoxicity using renal, apoptotic (caspase-3, caspase-8, and caspase-9 enzyme activities), and oxidative stress [nitric oxide (NO) and malondialdehyde (MDA)] markers; serum blood urea nitrogen (BUN) and creatinine levels; and histopathological examination. A total of 49 male Wistar albino rats were used (n = 7): control [saline, intraperitoneally (i.p.)], dimethyl sulfoxide (i.p.), VA [400 mg/(kg-day), i.p.], SLY100 [100 mg/(kg-day), i.p.], VA + SLY50 [50 mg/(kg-day), i.p.], VA + SLY100 [100 mg/(kg-day), i.p.], and VA + SLY200 [200 mg/(kg-day), i.p.]. SLY was administered once daily for 8 days. One day after the first treatment of SLY, VA administration was started and continued for 7 days. The levels of serum creatinine and BUN were evaluated using ELISA, caspase enzyme activities and levels of MDA and NO in the kidney tissues were evaluated by the colorimetric methods. The serum...

The ameliorating effect of silymarin against vancomycin-induced apoptosis and inflammation in rat liver

Güzel Kara, Sevda | Uçkun Şahinoğulları, Zuhal | Canacankatan, Necmiye | Antmen, Ş. Efsun | Kibar, Deniz

Silymarin (SL), a flavonolignan complex isolated from seeds of Silybum marianum (Asteraceae), is known for its hepatoprotective, anti-apoptotic, anti-inflammatory, and antioxidant activities. A glycopeptide antibiotic, Vancomycin (VA) which is used for the treatment of serious infections caused by multi-resistant Gram-positive microorganisms has been clinically used for a long time. The aim of the present study was to evaluate potential therapeutic efficiency of SL against VA-induced apoptosis and inflammation using apoptotic (caspase-3, -8, and, -9) enzyme activities) and inflammatory (Tumor necrosis factor-alpha (TNF-α)) markers, and histopathological examinations in rat liver. A total of 49 male Wistar albino rats was divided into 7 groups including control (saline, intraperitoneally (i.p.)), Dimethyl sulfoxide (i.p.), VA (400 mg/kg/day, i.p.), SL100 (100 mg/kg/day, i.p.), VA+SL50 (50 mg/kg/day, i.p.), VA+SL100 (100 mg/kg/day, i.p.), and VA+SL200 (200 mg/kg/day, i.p.). SL was administered once a daily for 8 days. One day after the first treatment of SL, VA administration was started and continued for 7 days. Hepatic TNF-α levels were evaluated by ELISA and hepatic caspase activities were evaluated according to the colorimetric method. Significantly increased caspase activities...

Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats

Uçkun, Zuhal | Güzel, Sevda | Canacankatan, Necmiye | Kibar, Deniz | Coşkun Yılmaz, Banu

Vancomycin (VCM), a glycopeptide antibiotic, is a drug widely used in severe infections. However, VCM induce notable nephrotoxic side effects. Naringenin (NAR) is a natural of flavonoid and are known as strongly antioxidant, nefroprotective, antiapoptotic, and anti-inflammatory. The purpose of this study was to determine the potential protective effects of NAR against VCM-induced nephrotoxicity by measuring apoptotic and oxidative stress markers and evaluating histopathological alterations in rats. For this purpose, we used male Wistar albino rats that divided into seven groups: (i) Control [saline, intraperitoneally (i.p.)], (ii) carboxymethyl cellulose (0.5% CMC, orally), (iii) VCM (400 mg/kg, i.p.), (iv) NAR100 (100 mg/kg, orally), (v) VCM + NAR25 (25 mg/kg, orally), (vi) VCM + NAR50 (50 mg/kg, orally), and (vii) VCM + NAR100 (100 mg/kg, orally) groups. VCM administration was started one day after the first treatment of NAR and continued across 7-day. Caspase-3, -8, and-9 activities and malondialdehyde (MDA) and nitric oxide (NO) levels were measured by colorimetric methods in the kidney tissues, creatinine, and blood urea nitrogen (BUN) levels were analyzed based on ELISA in serum. Caspase-3 and -8 activities, NO levels, serum creatinine and BUN levels were significantly high...