Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Sisplatin Nefrotoksisitesi Oluşturulan Sıçanların Plazma Glutatyon Peroksidaz, Süperoksit Dismutaz, Adenozin Deaminaz Aktiviteleri ve Nitrik Oksit Seviyelerine Ginkgo Biloba Ekstraktının Etkileri
THE EFFECTS OF GINKGO BILOBA EXTRACT ON PLASMA GLUTATHION PEROXIDASE, SUPEROXIDE DISMUTASE, ADENOSINE DEAMINASE AND NITRIC OXIDE LEVELS IN CISPLATIN-INDUCED NEPHROTOXICITY
Mukaddes GÜLEÇa, H. Ramazan YILMAZb, Mustafa IRAZc, Seda AĞLAMIŞc, Sadık SÖĞÜTd
aBiyokimya, cFarmakoloji AD, İnönü Üniversitesi Tıp Fakültesi, MALATYAbTıbbi Biyoloji ve Genetik AD, Süleyman Demirel Üniversitesi Tıp Fakültesi, ISPARTAdBiyokimya AD, Mustafa Kemal Üniversitesi Tıp Fakültesi, HATAY
Turkiye Klinikleri J Med Sci. 2004;24(6):585-91
Article Language: TR
Full Text
ÖZET
 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.

Anahtar Kelimeler: Sisplatin nefrotoksisitesi, ginkgo biloba, glutatyon peroksidaz, süperoksit dismutaz, adenozin deaminaz, nitrik oksit
ABSTRACT
 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<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.

Keywords: Cisplatin nephrotoxicity, ginkgo biloba, glutathione peroxidase, superoxide dismutase, adenosine deaminase, nitric oxide

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com