Enes KARAMAN, Munevver BARAN, Zeynep Burcin GONEN, Ozge GOKTEPE, Gozde Ozge ONDER, Eda OKUR, Erol KARAKAS, Arzu YAY

Sıçanlarda Asetaminofen Kaynaklı Uterin ve Fallop Tüpleri Hasarına Karşı Eksozomların Kullanımı Üzerine Deneysel Bir Çalışma

Asetaminofen (APAP), dünya çapında reçetesiz satın alınabilen ve kullanılabilen bir antipiretik ve analjezik ilaçtır. Önerilen maksimum dozdan daha yüksek bir APAP dozu, organ hasarı riskini artırabilir. Mezenkimal kök hücreler (MSC'ler), çeşitli insan dokularından izole edilir ve yararlı etkilerin esas olarak mezenkimal kök hücreden türetilen hüc- re dışı veziküllere (MSC-EV'ler) atfedildiği terapi için kullanılır. Bununla birlikte, hiçbir çalışma eksozomların APAP ile kombinasyon halinde koruyucu etkisine odaklanmamıştır. Bu nedenle bu çalışma APAP toksisitesine karşı eksozom almanın fallop tüpleri ve uterus üzerindeki koruyucu etkisini araştırmak amacıyla yapılmıştır. Kırk dişi Wistar albino sıçan (12-14 haftalık) rastgele dört eşit gruba ayrıldı: kontrol, APAP (1 g/kg APAP aldı), eksozom (30 μg eksozom aldı) ve APAP+eksozom grupları eş zamanlı olarak 1 g/kg APAP ve ardından üç gün sonra kuyruk damarından 30 ug ekso- zom enjeksiyonu yapıldı. Hayvanlar sakrifiye edildikten sonra histolojik ve immünohistokimyasal analizler için uterus ve fallop tüpleri çıkarıldı. Sonuçlar, eksozomların APAP'tan sonra uygulanmasının APAP'ın otofajik etkilerini azalttığını gösterdi. Ayrıca, eksozom tedavisi, otofaji belirteçlerinin (Beclin-1, p62 ve LC3) immünoreaktivite yoğunlukları üzerinde koruyucu bir etki sergiledi. Eksozomlarla yapılan tedavilerin uterus veya fallop tüpleri üzerinde herhangi bir olumsuz etkisi olmamıştır. APAP toksisitesinden sonra eksozomların uygulanması, APAP'ın otofaji etkisi yoluyla hücre ölümünü azaltabilir. Bu bileşiğin APAP'ın toksik etkilerini azaltabileceği öne sürülmektedir. Bu hiperanaljezik etkinin moleküler mekanizmasını değerlendirmek için ileri çalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

Ağrı, asetaminofen, eksozom, otofaji, sıçan

An Experimental Study on the Use of Exosomes against Acetaminophen-induced Uterine and Fallopian Tubes Damage in Rats

Acetaminophen (APAP) is an antipyretic and analgesic drug that can be bought and used without a prescrip- tion worldwide. A dosage of APAP greater than the maximum recommended dosage can increase the risk of organ damage. Mesenchymal stem cells (MSCs) are isolated from various human tissues and used for therapy, in which beneficial effects are attributed mainly to mesenchymal stem cell-derived extracellular vesicles (MSC-EVs). However, no study has focused on the protective effect of exosomes in combination with APAP. Therefore, the present study was carried out to investigate the protective effect of taking exosomes against APAP toxicity on the fallopian tubes and uterus. Forty female Wistar albino rats (12–14 weeks old) were randomly divided into four equal groups: control, APAP (received 1 g/kg APAP), exosome (received 30 μg of exosomes), and APAP+exosome groups that received simultane- ously 1 g/kg APAP and were followed three days later by a tail vein injection 30 μg of exosomes. The uterus and fallo- pian tubes were removed for histological and immunohistochemical analyses after the animals were sacrificed. The results showed that exosomes' administration after APAP decreased APAP's autophagic effects. Moreover, exosome treatment exhibited a protective effect on the immunoreactivity intensities of autuphagy markers (Beclin-1, p62, and LC3). The treatments with exosomes had no adverse effect on the uterus or fallopian tubes. The administration of exo- somes after APAP toxicity can decrease cell death through the autophagy effect of APAP. It is suggested that this com- pound can decrease the toxic effects of APAP. Further studies are needed to evaluate the molecular mechanism of this hyperanalgesic effect.

Keywords:

Autophagy, acetaminophen, exosome, pain, rat,

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