4-hidroksifenilboronik asitin HEPG2 hücre hattında asetaminofen ile indüklenen karaciğer hücre hasarı üzerine etkisinin araştırılması

Yıl 2022, , 507 - 513, 30.09.2022

Muhammet Çelik , Pelin Aydın

https://doi.org/10.30728/boron.1079589

Öz

Karaciğer; detoksifikasyon, metabolizma, sindirime yardımcı olan safra salgısını üretmek başta olmak üzere yüzlerce farklı iş yapan özel bir organdır. Karaciğer hastalıkları ve sonrasında gelişebilecek karaciğer yetersizliği insanlar için çok kritik bir klinik sorundur. Son yıllarda karaciğer hasarının kemoterapotiklerin, antiviral ilaçların ve bitkisel destekleyici ürün kullanımının artışı ile beraber insidansının arttığı görülmektedir. Bu nedenle günümüzde karaciğer hasarının tedavi edilebilmesi artık daha öncelikli olarak düşünülmektedir. Asetaminofen (APAP), dünyada en yaygın kullanılan, reçetesiz satılan analjezik ve antipiretik ilaçlarından biridir. Bununla beraber, aşırı dozda APAP alınmasına bağlı olarak karaciğer hasarı gelişebilir. APAP’ın N-asetil-benzokinonimin(NAPQI) metaboliti toksik etkinin ortaya çıkmasından sorumludur. NAPQI'nın hücre içi proteinlere, özellikle mitokondriyal proteinlere kovalent bağlanması, mitokondriyal oksidatif stresi ve nihayetinde hepatosit nekrozunu tetiklediği bilinmektedir. Bor içeren bileşiklerin antibakteriyel, antiviral, antioksidatif ve antiinflamatuvar özelliklerine sahip olduğu daha önceki çalışmalarda gösterilmiştir. Bor ve türevlerinin HIV, obezite, diabet ve kanser gibi hastalıkların tedavisinde faydaları bilinmektedir. Bu özellikleriyle antioksidan mekanizma üzerinden hepatosit nekrozu için umut vaat etmekte ve araştırılması gerekmektedir. Bu çalışmada, boronik asit türevi olan 4-hidroksifenilboronik asidin (4-OHFBA) APAP ile indüklenmiş karaciğer hasarındaki etkinliğinin araştırılması amaçlanmıştır. Elde edilen sonuçlara göre 4-OHFBA tedavisi ile yüksek AST ve ALT seviyelerinin düştüğü gözlemlenmiştir. Bu sonuçlar 4-OHFBA’nın karaciğer hasarının tedavisinde etkili olabileceğini göstermiştir.

Anahtar Kelimeler

4-hidroksifenilboronik asit, asetaminofen, HEPG2, karaciğer hasarı, 4-hidroksifenilboronik asit, asetaminofen, HEPG2, karaciğer hasarı

Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Investigation of the effect of 4-hydroxyphenylboronic acid on acetaminophen-induced liver cell injury in HEPG2 cell line.

Öz

The liver is a special organ that does hundreds of different jobs, especially in detoxification, metabolism, producing bile secretion that helps digestion. Liver diseases and subsequent liver failure is a very critical clinical problem for humans. Recently, it has been detected that the incidence of liver damage has increased with the increase in the use of chemotherapeutics, antiviral drugs and herbal supplements. Therefore, it is important to treat liver damage. Acetaminophen (APAP) is one of the most widely prescribed analgesic and antipyretic drug in the world. However, liver damage may develop due to an overdose of acetaminophen. The N-acetyl-benzoquinonimine (NAPQI) metabolite of APAP is responsible for the occurrence of the toxic effect. Covalent binding of NAPQI to intracellular proteins, especially mitochondrial proteins, is known to trigger mitochondrial oxidative stress and ultimately hepatocyte necrosis. It has been shown in previous studies that boron-containing compounds have antibacterial, antiviral, antioxidative and anti-inflammatory properties. The benefits of boron and its derivatives in the treatment of diseases such as HIV, obesity, diabetes and cancer are known. With these properties, it shows promise for hepatocyte necrosis through the antioxidant mechanism. In this study, it was aimed to investigate the efficacy of 4-hydroxyphenylboronic acid (4-OHFBA), a derivative of boronic acid, in APAP-induced liver injury. According to the results obtained, it was found that high AST and ALT levels decreased with 4-OHFBA treatment. These results showed that 4-OHFBA may be effective in the treatment of liver damage.

Anahtar Kelimeler

4-hydroxyphenylboronic acid, acetaminophen, HEPG2, liver damage, 4-hydroxyphenylboronic acid, acetaminophen, HEPG2, liver damage

Proje Numarası

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Kaynakça

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