Laboratuvar Hayvanlarında Deneysel Nefrotoksisite Modelleri

Abstract

Hastalıkların mekanizmalarını daha iyi anlamak ve etkili tedavi yöntemleri geliştirebilmek amacıyla in vivo ve in vitro modellerin kullanımı, modern tıbbın ve biyomedikal araştırmaların temel taşlarından biri olarak kabul edilmektedir. Deney hayvanları, bilimsel araştırmalar için vazgeçilmez bir gereklilik olarak karşımıza çıkmakta ve hastalıkların patofizyolojisini anlamada kritik bir rol oynamaktadır. Nefrotoksisite, böbrek dokusunun çeşitli kimyasal maddeler veya ksenobiyotikler tarafından maruz kaldığı zararlı etkileri ifade eder. Bu durum, böbrek hasarına yol açabilecek birçok farklı madde tarafından tetiklenebilir. Örneğin, antibiyotikler (özellikle aminoglikozidler ve vankomisin), non-steroidal antiinflamatuar ilaçlar (NSAID'ler), antiviral ilaçlar, tıbbi görüntülemede kullanılan kontrast maddeler, ağır metaller (kurşun ve cıva) ve kemoterapi ilaçları, böbrek dokusu üzerinde toksik etkiye sahip maddeler arasında yer alır. Böbrekler, bu ilaçlar ve kimyasalların toksik etkilerine karşı oldukça savunmasızdır ve bu savunmasızlık, ciddi böbrek hasarlarına yol açabilir. Ksenobiyotikler, özellikle ilaçlar, akut böbrek hasarı (ABH), kronik böbrek hastalığı (KBH), akut böbrek yetmezliği (ABY) ve son dönem böbrek hastalığı (SDBH) gibi ciddi sağlık sorunlarının önde gelen nedenleri arasındadır. İlaç kaynaklı nefrotoksisite, genellikle üç ana mekanizma üzerinden incelenir: Proksimal tübüler hasar ve akut tübüler nekroz (ATN), kristal formdaki ksenobiyotik veya ilaç metabolitlerinin neden olduğu tübüler tıkanıklık ve ilaçlar ile metabolitlerinin indüklediği interstisyel nefrit. Böbrek fonksiyonlarını gösteren biyokimyasal parametrelerdeki değişiklikler, nefrotoksisitenin tanısında kritik bir rol oynar. Bu derlemede, deneysel nefrotoksisite modelleri, tanısında kullanılan biyobelirteçler ve bu biyobelirteçlerin klinik önemleri ayrıntılı olarak ele alınmıştır.

Keywords

• Böbrek
• Folik Asit
• Gentamisin
• Hayvanlar
• Laboratuvar

Experimental Nephrotoxicity Models in Laboratory Animals

Abstract

The use of in vivo and in vitro models to better understand disease mechanisms and develop effective treatment methods is considered one of the cornerstones of modern medicine and biomedical research. Experimental animals are an indispensable necessity for scientific research, playing a critical role in understanding the pathophysiology of diseases. Nephrotoxicity refers to the harmful effects exerted on kidney tissue by various chemical substances or xenobiotics. This condition can be triggered by a wide range of substances capable of causing kidney damage. For instance, antibiotics (particularly aminoglycosides and vancomycin), non-steroidal anti-inflammatory drugs (NSAIDs), antiviral agents, contrast agents used in medical imaging, heavy metals (such as lead and mercury), and chemotherapeutic drugs are among the substances with toxic effects on kidney tissue. The kidneys are highly vulnerable to the toxic effects of these drugs and chemicals, and this vulnerability can lead to significant kidney damage. Xenobiotics, particularly drugs, are among the leading causes of severe health issues such as acute kidney injury (AKI), chronic kidney disease (CKD), acute renal failure (ARF), and end-stage renal disease (ESRD). Drug-induced nephrotoxicity is generally examined through three main mechanisms: proximal tubular injury and acute tubular necrosis (ATN), tubular obstruction caused by crystal-forming xenobiotics or drug metabolites, and interstitial nephritis induced by drugs and their metabolites. Changes in biochemical parameters reflecting kidney function play a critical role in diagnosing nephrotoxicity. This review provides a detailed examination of experimental nephrotoxicity models, biomarkers used in diagnosis, and the clinical significance of these biomarkers.

Keywords

• Kidney
• Folic Acid
• Gentamicin
• Animals
• Laboratory
• Nephritis

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