Journal of Literature Pharmacy Sciences

Vakalar Perspektifinde Bitkisel Ürünler ve Hepatotoksisite
Herbal Products and Hepatotoxicity in the Perspective of Cases
İçim GÖKKAYAa, Gülin RENDAa
aKaradeniz Teknik Üniversitesi Eczacılık Fakültesi, Farmakognozi ABD, Trabzon, TÜRKİYE
J Lit Pharm Sci. 2021;10(2):133-52
doi: 10.5336/pharmsci.2020-78223
Article Language: TR
Full Text
ÖZET
 Bitkiler, çok eski dönemlerden beri hastalıkların önlenmesinde ve tedavisinde kullanılmaktadır. Bitkisel ürün kullanımı, ilaca bağlı karaciğer hasarının en yaygın nedenlerinden biri olarak görülmektedir. Retrospektif çalışmalarda bazı bitkilerin ve bitkisel preparatların kullanımı, karaciğer hasarıyla ilişkilendirilmiştir. Bu derlemede, 1976 yılından itibaren bitkisel ürün kullanımı sonucu geliştiği belirtilen 60 hepatotoksisite olgusu, hasta öyküleri, muayene, laboratuvar ve varsa biyopsi bulguları incelenmiştir. Bu vakalarda yaygın olarak kullanılmış olduğu belirlenen Aloe vera (L.) Burm.f., Atractylis gummifera Salzm.ex L., Camellia sinensis (L.) Kuntze, Chelidonium majus L., Cimicifuga racemosa (L.) Nutt., Mentha pulegium L. ve Hedeoma pulegioides (L.) Pers., Piper methysticum G.Forst., Polygonum multiflorum Thunb., Valeriana officinalis L.'nin, pirolizidin alkaloitleri içeren bitkilerle Teucrium L. türlerinin hepatotoksisiteden sorumlu bileşenleri, hepatotoksisite oluşturma mekanizmaları ve mevcut tedavi yaklaşımları derlenmiştir. Bitkilerin genelinin hepatotoksisite oluşturma mekanizması belirsiz olmakla birlikte, patogenezi çoğunlukla idiyosenkratik tip reaksiyonlar oluşturmaktadır. Bitkilere bağlı karaciğer hasarının tanısında, altın bir standart bulunmamakta ve dışlama kriterleri esas alınmaktadır. Karaciğer hasarının tipinin belirlenmesinde R değeri hesaplanmaktadır ve bitkilerin çoğunlukla hepatoselüler hasar olmak üzere kolestatik ve miks tipte hasar oluşturabilecekleri bildirilmiştir. Teşhis için çeşitli skorlama sistemleri geliştirilmiştir ve en yaygın kullanılanı Roussel Uclaf Nedensellik Değerlendirme skorlamasıdır. Vakaların çoğunda, bitkisel ürünün geri çekilmesinden sonra karaciğer testlerinde iyileşmeler gözlemlenmiştir. Bununla birlikte birçok vakanın sonucunda organ yetersizliği ve ölüm görülmesi, hepatotoksisite ile ilişkilendirilen bitkiler arasında A. gummifera, pennyroyal yağı gibi şiddetli hasara neden olan ürünlerle halk arasında yaygın olarak tüketilen C. sinensis ve Teucrium sp. gibi bitkilerin bulunması dikkat çekicidir. Bitkisel ürün kullanımıyla ilişkili hepatotoksisite riskinin azaltılabilmesi için ürün kalitesi ve denetiminin sağlanması ve ürünlerin konuyla ilgili eğitim almış sağlık personeli danışmanlığında kullanılmaları gerekmektedir.

Anahtar Kelimeler: İlaca bağlı karaciğer hasarı; bitkisel ürün; akut hepatit
ABSTRACT
 Plants have been used in the prevention and treatment of diseases since ancient times. Herbal product use is one of the common causes of drug-induced-liver-injury. In retrospective studies the use of some herbs and herbal preparations has been associated with liver damage. In this review, 60 hepatotoxicity cases, reported as a result of the use of herbal products since 1976, were examined as well as anamnesis, examination, laboratory and biopsy findings. Aloe vera (L.) Burm.f., Atractylis gummifera Salzm.exL., Camellia sinensis (L.) Kuntze, Chelidonium majus L., Cimicifuga racemosa (L.) Nutt., Mentha pulegium L. and Hedeoma pulegioides (L.) Pers., Piper methysticum G.Forst., Polygonum multiflorum Thunb., Valeriana officinalis L., pyrolysidine alkaloid plants, Teucrium L. species' components responsible for hepatotoxicity, hepatotoxicity mechanisms and current treatment approaches are compiled. Although the mechanism of general hepatotoxicity is uncertain, pathogenesis is mostly create of idiosyncratic type reactions. There isn't a gold standard in diagnosis and is based on exclusion criteria. The R value is calculated to determine the type of liver damage, and it has been reported that plants can cause cholestatic and mixed type damage, mostly hepatocellular damage. Various scoring systems have been developed for diagnosis and the most commonly used is Roussel Uclaf Causality Assessment Method scoring. Improvements in liver tests were observed in most cases after withdrawal of herbal product. It is noteworthy that organ failure and death are observed as a result of many cases and finding plants that cause severe damage such as A. gummifera, Pennyroyal oil, and widely consumed by public such as C.sinensis and Teucrium sp. To reduce the risk of hepatotoxicity, product quality and control should be ensured and the products should be used under supervision of health personnel.

Keywords: Drug induced liver injury; herbal product; acute hepatitis
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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