İlaçlar İle İndüklenen Fosfolipidozis ve Katyonik Amfifilik İlaçlar

Year 2018, Volume: 38 Issue: 2, 65 - 75, 15.06.2018

Tuğçe Boran Ayşe Tarbin Jannuzzi Buket Alpertunga

Abstract

Fosfolipidozis bir lipid depo bozukluğudur ve karaciğer, böbrek, beyin ve akciğer gibi dokularda fosfolipidlerin aşırı birikimi ile karakterizedir. Hücrelerde fosfolipid birikimi fosfolipidozisin önemli histopatolojik biyobelirteçleri olarak da kullanılan köpüklü sitoplazmaya, sitoplazmik vakuollere ve lamellar cisimciklerin oluşmasına neden olur. Katyonik amfifilik ilaçlar (KAİ’lar)’ın fosfolipidozis geliştirme potansiyellerinin olduğu bilinmektedir. KAİ’lar hidrofobik bir halka yapısı ile amin grubu içeren hidrofilik bir yan zincire sahiptirler. Sahip oldukları hidrofobik yapı sayesinde membranları kolaylıkla geçerler ve lizozomların asit ortamında katyonik hale geçip lizozomlarda tutulurlar. İlaçlar ile indüklenen fosfolipidozisin fonksiyonel olarak nasıl bir etkiye neden olduğu ve mekanizması tam olarak bilinmemektedir. Ancak, fosfolipidozis ile değişmiş hücre fonksiyonları ve hücre ölümü arasında olası bir ilişki bulunması nedeniyle toksik bir yanıt oluşturduğu düşünülmekte ve fosfolipidozis gelişimi advers etki olarak kabul edilmektedir.

Keywords

İlaçlar ile indüklenen fosfolipidozis, katyonik amfifilik ilaçlar, ilaç advers etkileri

Drug Induced Phospholipidosis and Cationic Amphiphilic Drugs

Abstract

Phospholipidosis is a lipid storage disorder and it is characterized by excessive accumulation of phospholipids in tissues such as liver, kidney, brain and lung. Accumulation of phospholipid in the cells leads to foamy cytoplasm, cytoplasmic vacuoles and lamellar bodies which are also used as important histopathological biomarkers of phospholipidosis. Cationic amphiphilic drugs (CADs) are known to have a potential for development of phospholipidosis. CADs have a hydrophobic ring structure and hydrophilic side chain which contains an amine group. Because of their hydrophobic structure, CADs can pass through the membrans easily and get trapped in the lysosomes thereby become cationic in the acidic environment of lysosomes. The mechanism and the functional effects of drug induced phospholipidosis are not fully understood. However, phospholipidosis is thought to be a toxic response due to a relationship between cell death and altered cell functions, and the development of phospholipidosis is considered as an adverse reaction. 

Keywords

Drug induced phospholipidosis, cationic amphiphilic drugs, drug advers effects

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