Journal of Literature Pharmacy Sciences

.: REVIEW
Toksikolojide İn Vitro Karaciğer Modelleri
In Vitro Liver Models in Toxicology
Pınar ERKEKOĞLUa, Belma KOÇER GÜMÜŞELa
aFarmasötik Toksikoloji AD, Hacettepe Üniversitesi Eczacılık Fakültesi, Ankara, TÜRKİYE
J Lit Pharm Sci. 2019;8(1):1-17
doi: 10.5336/pharmsci.2018-61664
Article Language: TR
Full Text
ÖZET
 Karaciğer organizmanın temel metabolik işlevlerinin gerçekleştiği organdır. Birçok kimyasal maddenin hepatotoksik olduğu bilinmektedir. Bir kimyasal maddenin in vivo olarak karaciğer hasarı yapabilme kapasitesi; bu maddenin alımı, biyotransformasyonu ve eliminasyonu sırasında geçirdiği bir seri kompleks hücresel prosese bağlıdır. Ayrıca, karaciğer hasarı yapan pek çok kimyasal madde için hayvan modellerinden elde edilen bilgilerin insana tam olarak ekstrapole edilmesi bazı durumlarda uygun değildir. Bu durumda, in vitro karaciğer sistemlerinin potansiyel hepatotoksik bileşiklerin belirlenmesi ve bunların yarattığı hepatotoksisitenin altında yatan mekanizma veya mekanizmaların araştırılması açısından daha iyi bir deneysel yaklaşımı sağladığı belirtilmektedir. En sık kullanılan in vitro karaciğer modelleri arasında; izole perfüze organ parçaları, karaciğer dilimleri, subselüler fraksiyonlar ve izole ve kültür hepatositler gelmektedir. Son 20-30 yıldır insan veya hayvanlardan elde edilen diferansiye hepatositlerin ve karaciğer dilimlerinin hazırlanma ve kültürlenmeleriyle ilgili çok büyük gelişmeler sağlanmıştır. Ayrıca, izole hepatositlerin ilaç metabolizması ve toksisite çalışmalarında sağlayabilecekleri yararlar hakkında önemli araştırmalar yapılmıştır. Ancak, başta ilaç geliştirme çalışmaları olmak üzere, in vitro çalışmalar in vivo çalışmalara henüz tam bir alternatif değildir. Ayrıca, kültür hepatositlerinde gözlenen erken fenotipik değişiklikler, düşük proliferasyon kapasiteleri ve insan hepatositlerinin bulunma zorlukları gibi bazı sınırlamalar bulunmaktadır. Gelecekte bu çalışmalardan beklenen en büyük gelişme kültür koşullarının iyileştirilerek in vivo koşulları daha iyi taklit edebilmesi ve bu koşullarla daha büyük korelasyon oluşturmasıdır. Bu çalışma kapsamında, toksikolojide kullanılan in vitro karaciğer modellerinden söz edilerek, her modelin kullanım koşulları, avantaj ve dezavantajlarının anlatılması amaçlanmıştır.

Anahtar Kelimeler: İn vitro teknikler; karaciğer; hepatositler; hücresel yapılar
ABSTRACT
 Liver is the organ where the basic metabolic functions of the organism is actualized. Several chemicals are known to be hepatotoxic. The capacity of a chemical to cause liver damage depends on a series of complex biological processes during its uptake, biotransformation and elimination. In addition, for several liver damaging chemicals, the extrapolation of information obtained from animal models to humans is not appropriate in some situations. Under these circumstances, in vitro liver systems provide a better experimental approach for determining the hepatotoxic substances and their mechanism/s of hepatotoxicity. The most widely used in vitro liver models are isolated perfused organ parts, liver slices, subcellular fractions and isolated and cultured hepatocytes. In the last twenty and thirty years, the preparation and culturing of the differentiated hepatocytes and liver slices obtained from animals and humans have intensively developed. Moreover, important research on the advantages of the use of isolated hepatocytes in drug metabolism and toxicity studies have been performed. However, in vitro studies are not still an alternative to in vivo studies, particularly in the field of drug development. In addition, the phenotypic changes observed in cultured hepatocytes, their proliferation capacity and the difficulty in finding human hepatocytes are still the limitations. In the future, the highly expected development is the recruitment of culture conditions for these models to highly mimic in vitro conditions and provide high correlations. In this review, I will mainly focus on in vitro liver models used in toxicology, their utilixation, advantages and disadvantages.

Keywords: In vitro techniques; liver; hepatocytes; cellular structures
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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