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 probable relationship between cell death and altered cell functions, and the development of phospholipidosis is considered as an adverse reaction. Key words: Drug induced phospholipidosis, cationic amphiphilic drugs, drug advers effects OZET Fosfolipidozis bir lipid depo bozuklugudur ve karaciger, bobrek, beyin ve akciger gibi dokularda fosfolipidlerin asiri birikimi ile karakterizedir. Hucrelerde fosfolipid birikimi fosfolipidozisin onemli histopatolojik biyobelirtecleri olarak da kullanilan kopuklu sitoplazmaya, sitoplazmik vakuollere ve lamellar cisimciklerin olusmasina neden olur. Katyonik amfifilik ilaclar (KAI’lar)’in fosfolipidozis gelistirme potansiyellerinin oldugu bilinmektedir. KAI’lar hidrofobik bir halka yapisi ile amin grubu iceren hidrofilik bir yan zincire sahiptirler. Sahip olduklari hidrofobik yapi sayesinde membranlari kolaylikla gecerler ve lizozomlarin asit ortaminda katyonik hale gecip lizozomlarda tutulurlar. Ilaclar ile induklenen fosfolipidozisin fonksiyonel olarak nasil bir etkiye neden oldugu ve mekanizmasi tam olarak bilinmemektedir. Ancak, fosfolipidozis ile degismis hucre fonksiyonlari ve hucre olumu arasinda olasi bir iliski bulunmasi nedeniyle toksik bir yanit olusturdugu dusunulmekte ve fosfolipidozis gelisimi advers etki olarak kabul edilmektedir. Anahtar kelimeler: Ilaclar ile induklenen fosfolipidozis, katyonik amfifilik ilaclar, ilac advers etkileri