The effects of ginkgo biloba extract on plasma glutathion peroxidase, superoxide dismutase, adenosine deaminase and nitric oxide levels in cisplatin-induced nephrotoxicity

Amaç: Sisplatin (CDDP) geniş spekturumlu platin türevi bir antineoplastik ajandır. Kuvvetli nefrotoksisite riskinden dolayı tedavide kullanımı oldukça kısıtlıdır. CDDP’nin böbrek dokusunda yaptığı hasarın altında yatan mekanizma büyük oranda reaktif oksijen ürünleri (ROS)’ne bağlıdır. Ginkgo biloba ekstraktı (GBE)= Egb 761, birçok organ ve dokunun birbirinden farklı ama ortak olarak serbest radikallerin öncelikli rol oynadığı patolojilerinde kullanılmakta olup tedavide faydalı etkisi olduğu görülmüştür. Bu çalışma GBE’nin sisplatin nefrotoksisitesine karşı koruyucu etkisinin olup olmadığını tespit etmek amacıyla planlanmıştır. Gereç ve Yöntemler: Bu çalışmada erkek Sprague Dawley sıçanlar (60 günlük) kullanıldı. Hayvanlar rastgele seçilerek 4 gruba ayrıldı: Kontrol grubu (n= 7), IP 7 mg/kg’dan tek doz CDDP (Cisplatin, Ebewe) uygulanan grup (n= 8), CDDP ile birlikte IP 10 mg/kg E-vit (Evigen-Aksu) verilen grup (n= 9), CDDP ile birlikte oral 100 mg/kg GBE uygulanan grup (n= 7). Deneysel işlemlerden 10 gün sonra hayvanların kanları alınarak uygulanan ajanların plazma oksidan/antioksidan sisteme olan etkileri araştırıldı. Bulgular: Veriler istatistiksel olarak incelendiğinde; CDDP alan sıçanların plazma glutatyon peroksidaz (GSH-Px) aktivitesinde azalma söz konusu iken, adenozin deaminaz (ADA) aktivitesinde ve nitrik oksit (NO) değerlerinde artışa rastlanmıştır. Plazma süperoksit dismutaz (SOD) aktivitesinde, gruplar arasında herhangi bir değişiklik olmamıştır. CDDP + E-vit verilmesi ile GSH-Px ve ADA aktivitelerinde kontrole yakın olmak üzere NO değerlerinde de bir düzelme gözlenmiştir. CDDP + GBE alan grubun GSH-Px aktiviteleri sadece CDDP alan gruba göre anlamlı derecede artmıştır (p< 0.014). GBE aynı zamanda CDDP ile artmış olan ADA ve NO değerlerinde istatistiksel olarak anlamlı olmayan belirgin bir azalma sağlamıştır. Sonuç: Bu sonuçlara göre CDDP ile oluşturulan nefrotoksisitenin temelinde hücre savunma sisteminin bozulması söz kosudur. Antioksidan özelliği olan GBE, burada kısmen koruyucu bir etkinlik göstermiştir. CDDP nefrotoksisitesinde GBE’nin kesin tedavi edici bir ilaç olarak değerlendirilebilmesi için henüz çok erkendir. Bu nedenle farklı doz, farklı süre ve farklı denek sayılarıyla yeni çalışmaların yapılması uygun olacaktır.Objective: Cisplatin (CDDP), derived from platinium, is a broad-spectrum antineoplastic agent. It has not commonly been used as a therapeutic agent because of its nephrotoxicity risk. The underlying mechanism in nephrotoxi-city has been attributed to reactive oxygen species (ROS). Gingko biloba extract (GBE, Egb 761) has been shown to be effective on some organ and tissue pathologies induced by ROS. The aim of this experimental study was to determine whether antioxidant GBE has a preventive effect on nephrotoxi-city induced by CDDP through oxidative damage. Material and Methods: Male Sprague Dawley rats (60 days old) were used in the experiments. Rats were randomly assigned to one of four groups: control or untreated rats (n=7); rats treated with i.p. injection in a single dose of 7 mg/kg body wt CDDP (Cisplatin, Ebewe) (n=8); rats treated with CDDP plus i.p. injection of 10 mg/kg body wt vitamin E (Evigen-Aksu, Turkey) (n=9); and rats treated with CDDP plus oral administration of GBE in a dosage of 100 mg/kg body wt (n=7). After 10 days of experimental procedure, animals were euthanized by bleeding, kidneys were removed and oxidant and antioxidant parameters were examined to determine the effects of agents as applied to the rats. Results: In treated rats, the activity of plasma glutathion peroxidase (GSH-Px) was decreased, but adenosine deaminase (ADA) and nitric oxide (NO) levels were increased with CDDP. The activity of superoxide dismutase (SOD) remained unchanged in all study groups. Upon treating the rats with CDDP + vit E, the activities of GSH-Px and ADA, and the level of NO were improved. In the case of CDDP + GBE application, we determined an increased activity of GSH-Px in comparison with the rats treated with CDDP (p&lt;0.014). GBE also decreased the levels of ADA and NO, which were increased in the CDDP-treated group. Conclusion: In keeping with the results, the main underlying mechanism in CDDP-induced nephrotoxicity appears to be due to renal tubular cell damage. GBE appeared to induce a beneficial therapeutic effect in this study. However, we can not yet consider GBE to be a new therapeutic agent in CDDP nephrotoxicity until further studies with various doses, different time intervals, and more animal numbers have been provided

The role of Kallikrein10 (KLK10) polymorphism in prostate cancer susceptibility

Purpose: The present study aims to investigate the potential role of Kallikrein 10 (KLK10) genotype and allele frequencies in predisposition to prostate cancer. Materials and methods: KLK10 (rs7259451) gene polymorphisms were determined by real-time polymerase chain reaction analysis in patients with prostate cancer (n=69) and controls (n=76). Results: KLK10 gene frequencies were significantly different in the case and control groups (P = .028). GG carriers were significantly higher in the control group (P = .034), whereas TT carriers were higher in the prostate cancer group (P = .033). Furthermore, The patients with GG genotype had the lowest PSA levels while TT carriers had the highest (P = .005). Conclusion: According to the results, we suggested that carrying variant T allele and also carrying homozygote TT genotype could be a potential risk, while ancestral homozygote GG genotype and G allele are risk reducing factors for prostate cancer.No sponso

Investigation of catechol-o-methyltransferase (comt) gene Val158Met polymorphism in ovarian cancer

Objective: Catechol-o-methyltransferase (comt), the product of the COMT gene, detoxifies the carcinogenic catechol estrogens. The aim of the present study was to examine the relationship between comt Val158Met polymorphism and the risk of ovarian cancer. Material and methods: The study groups consist of 94 individuals as a patients group with ovarian cancer (n=47) and control group (n=47). The allele and genotype frequencies were determined according to Hardy-Weinberg equilibrium (HWE). The allele and genotype frequencies. determined according to HWE. Genetic analysis were performed by real-time-polymerase chain reaction instrument, and the statistical analysis were performed by SPSS program. Results: Although no significant relationship was obtained among groups (p=0.413) regarding comt gene Val158Met polymorphism, the genotype frequencies for comt Val158Met (rs4860) polymorphism in groups was homozygote wild type GG genotype 25.5%, heterozygote GA genotype 46.8%, homozygote mutant AA genotype 27.7%. Conclusion: This study is the first to investigate the relationship between ovarian cancer and the Val158Met polymorphism in the comt gene in a Turkish population. No statistically significant relationship was identified among genotypes belonging to the patient and control groups although sample sizes were relatively small and the analysis should be repeated in a larger cohort.No sponso

The effect of vitamine-E on metabolic enzyme activities during cisplatin-induced nephrotoxicity in rats

Amaç: Sisplatin insanlarda baş, boyun, akciğer, testis, ovaryum gibi bir çok solid tümörde etkili bir antitümör ilaç olarak kullanılmaktadır. Tedavi esnasında serbest oksijen radikalleri üreterek başta böbrek olmak üzere bir çok organda toksisiteye neden olduğu için doz kısıtlamasına gidilmektedir. E vitamini (E vit) serbest radikal süpürücü bir antioksidandır. Bu çalışmada sıçanlarda sisplatine bağlı akut renal yetmezlik modelinde E vitamininin koruyucu etkilerinin olup olmadığı araştırıldı. Gereç ve Yöntem: Sıçanlar 3 gruba ayrıldı; Grup-I (n=7), 3. gün serum fizyolojik intraperitoneal (i.p.) olarak uygulandı. Grup-II (n=8), 3. gün tek doz 7 mg/kg sisplatin i.p. olarak uygulandı. Grup-III (n=9), sisplatin+E vit, deney süresince (toplam 7 gün) her gün i.p. olarak E vit 10 mg/kg 1x1 dozunda ve 3. Günde 7 mg/kg sisplatin tek doz halinde i.p. olarak verildi. Sisplatin verilişinden 5 gün sonra sıçanların böbrekleri genel anestezi altında alındı. Doku homojenize edildi ve supernatant elde edildi. Süpernatantdan hekzokinaz (HK), glukoz-6-fosfat dehidrogenaz (G6PD), laktat dehidrogenaz (LDH) ve malat dehidrogenaz (MDH) aktiviteleri spektro-fotometrik olarak ölçüldü. Bulgular: Tek doz olarak verilen sisplatinin kontrol grubuna göre diğer iki grupta, MDH dışındaki diğer enzimlerin aktivitelerinde istatistiksel olarak anlamlı artışa neden olduğu görüldü. Sisplatin grubu ile sisplatin+E vit grubu karşılaştırıldığında, E vit uygulanmasının HK, G6PD enzim aktivitelerinde istatistiksel olarak artışa neden olurken MDH aktivitesinde azalmaya neden olduğu görüldü. Sisplatin uygulanan grupların böbrek dokusu LDH aktiviteleri arasında anlamlı bir değişme gözlenmedi. Sonuç: Sisplatinin böbrek dokusunda oluşturduğu hasar esnasında glikoliz ve pentoz fosfat metabolitik yollarının hasarı sınırlamak amacıyla aktive olduğu ve E vit'in bu durumu daha da artırmasıyla korumaya çalıştığı gözlendi. Bu sonuçlar sisplatinin istenmeyen yan etkilerinin daha etkili, ekonomik ve kolay uygulanabilir ilaçlarla önlenebileceği veya azaltılabileceği konusunda alternatifler bulmada yol gösterici olabilir.Purpose: Cisplatin is used as an effective antitumor agent for treatment of many solid tumors such as head, neck, lung, testis, ovaryum in human. Its usage is limited due to its toxicity to many organs including kidneys via free oxygen radicals. Vitamin E (Vit E) is an antioxidant agent. The aim of this study was to investigate whether Vit E is a protective agent against cisplatin induced acute renal failure or not. Materials and Methods: Rats were divided into three groups: Group-I, %0.9 Nad solution was injected every day during the experimental procedure (n=7); Goup-II, cisplatin was administrated single i.p. dose of 7 mg/kg at 3rd day os the experimental procedure (n=8); Group-Ill, Vit E was injected every day i.p. dose of 10 mg/kg in addition to cisplatin injection (n=9). The kidneys were removed under anesthetized 5 days after the cisplatin administration. Tissue was homogenized and supernatant was sepa-rated. The activities of hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydro-genase (LDH) and malate dehydrogenase (MDH) were measured spectrophotometrically from super-natant. Results: Single dose cisplatin in two study group caused statistically increase activities of all enzymes except MDH in comparison with control group. Vit E treatment resulted in higher activities of HK and G6PD, but lower activity of MDH than only cisplatin administration. There was no significant difference in LDH activity between groups. In conclusion, glycolisis and pentose phosphate metabolic ways were activated during cisplatin induced renal injury and Vit E was try to protect the tissue from injury-by increasing the activities much more. Conclusion: These results may help to show that cisplatin induced undesired toxicities may be preven-ted or decreased by cheapest ways

Investigation of circulating miRNA-133, miRNA-26, and miRNA-378 as candidate biomarkers for left ventricular hypertrophy

Background/aim: Left ventricular hypertrophy (LVH) involves increased muscular mass of the left ventricle due to increased cardiomyocyte size and is caused by cardiomyopathies. Several microRNAs (miRNAs) have been implicated in processes that contribute to heart disease. This study aimed to examine miRNA-133, miRNA-26 and miRNA-378 as candidate biomarkers to define prognosis in patients with LVH. Patients and methods: The study group consisted of 70 patients who were diagnosed with LVH and 16 unaffected individuals who served as the control group. Real-time polymerase chain reaction (RT-PCR) was used to analyze serum miRNA-133, miRNA-26, and miRNA-378 expression levels in LVH patients and the control group. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capability of miRNA-378. Results: When crossing threshold (CT) values were compared between patient and control samples, we found that there were no statistically significant differences in miRNA-133 and miRNA-26 CT values, while the miRNA-378 expression was significantly increased in LVH patients. ROC analysis demonstrated that the expression levels of miRNA-378 (AUC=0.484, p=0.0013) were significantly different between groups. Conclusion: We observed a statistically significant relationship between miRNA-378 expression levels and LVH, suggesting that circulating miRNA-378 may be used as a novel biomarker to distinguish patients who have LVH from those who do not.No sponso