Tavşanlarda Yapılan Asetaminofen Toksikoloji Modelinde N-Asetilsistein ve Resveratrol Tedavilerinin Karşılaştırılması

Year 2022, , 282 - 289, 25.12.2022

Hasan Gazi Uyar , Aysegül Bayır , Hasan Kara , Pınar Karabağlı Abdullah Sivrikaya , Ali Unlu

https://doi.org/10.46332/aemj.1060025

Abstract

Amaç: Asetaminofen güvenli bir analjezik ilaçtır fakat yüksek dozlarda akut karaciğer hasarına neden olmaktadır. Asetaminofen intoksikasyonunda tedavisinde N-asetil sistein (NAC) kullanılmaktadır. Resveratrolun (RES), asetaminofen intoksikasyonu modellerinde kullanılabileceği gösterilmiştir. Çalışmamızda amaç, asetaminofen intoksikasyonunda NAC ile resveratrol tedavilerinin etkinliğinin karşılaştırmaktır.

Araçlar ve Yöntem: Çalışmamızda 6’sı kontrol grubunda olmak üzere, 28’ i 4 farklı çalışma grubunda olmak üzere toplam 34 tavşan kullanıldı. Asetaminofen (APAP) (n=7) grubunda hayvanlara 2 gr/kg asetaminofen orogastrik tüp aracılığıyla verildi. Asetaminofen+N-asetilsistein (APAP+NAC) (N=7) grubunda hayvanlara 2 gr/kg asetaminofen orogastrik tüp aracılığıyla verildi ve takibinin 1. saatinde 150 mg/kg NAC intramüsküler (i.m) uygulandı. Asetaminofen+resveratrol (APAP+RES) (N=7) grubunda hayvanlara 2 gr/kg asetaminofen orogastrik tüp aracılığıyla verildi ve takibinin 1. saatinde orogastrik tüple 100 mg/kg resveratrol verildi. Asetaminofen+Nasetilsistein+Resveratrol (APAP+NAC+RES) (N=7) grubunda ise hayvanlara 2 gr/kg asetaminofen oro-gastrik tüp aracılığıyla verildi ve takibinin 1. saatinde orogastrik tüple 100 mg/kg resveratrol verildi ve 150 mg/kg NAC i.m uygulandı. ALT, AST, total GSH ve kan asetaminofen düzeyleri çalışıldı. Hayvanlar 24. saatte sakrifiye edildi. Karaciğer dokusu histopatolojik inceleme için kullanıldı.

Bulgular: Sonuçlarımızda 12 saat GSH düzeyi APAP+NAC grubunda APAP+RES grubuna göre istatiksel olarak anlamlı bulundu (p=0.007). Histopatolojik çalışmada, apoptozis için kullandığımız HSCORE düzeyi kontrol grubunda APAP grubuna göre istat-iksel olarak daha düşük tespit edildi (p=0.007). Bu sonuç asetaminofen toksisisitesi karaciğer hücrelerinde apoptozisi tetiklediğini gösteriyor.

Sonuç: Resveratrol asetaminofen toksisitesi tedavisinde NAC’a alternatif bir tedavi seçeneği olabilir.

Keywords

Asetamınofen, parasetamol, NAC, Toksisite, Resveratrol

Supporting Institution

yok

Project Number

selçuk üniversitesi deneysel tıp ve araştırma merkezi onay no:2015/77

Comparison of N-Acetyl Cysteine and Resveratrol Treatments in Acetaminophen Toxicity Model in Rabbits

Abstract

Purpose: Acetaminophen is safe analgesic drug but it may cause hepatic failure in high doses. N-acetyl cysteine (NAC) is used in the treatment of acetaminophen intoxication. Resveratrol may be used in experimental acetaminophen intoxication models. Purpose, compare the efficacy of NAC and resveratrol treatments in acetaminophen intoxication.

Materials and Methods: We used 34 rabbits. Six rabbits were included in control group, and 7 rabbits were enrolled in other groups Asetaminophen (APAP) (N=7) group. The animals were administered 2 g/kg of acetaminophen by an orogastric tube. Asetaminophen+N-acetylcysteine (APAP+NAC) (N=7) group, 150 mg/kg NAC was administered intramuscular (i.m) to animals at 1st hour following 2 g/kg of acetaminophen administration by orogastric tube. Asetaminophen+resveratrol (APAP+RES) (N=7) group, animals received 100 mg/kg resveratrol by orogastric tube at 1st hour following oral administration of 2 g/kg of acetaminophen by orogastric tube. e. Asetaminophen+N-acetyl cysteine+resveratrol (APAP+NAC + RES) (N=7) group, animals received 100 mg/kg resveratrol by orogastric tube and 150 mg/kg NAC i.m at 1st hour following oral administration of 2 g/kg of acetaminophen by orogastric tube. ALT, AST, GSH, and acetaminophen levels were measured. Animals were sacrificed at the 24th hour. Liver samples were obtained for histopathological examination.

Results: According to our results, the GSH level at 12th hour was significantly different between APAP+NAC group and APAP+RES group (p=0.007). In histopathological examination, HSCORE level we used for apoptosis was statistically significantly lower in control group than in APAP group (p=0.007). Its supports that acetaminophen toxicity triggers apoptosis in liver cells.

Conclusion: Resveratrol may be an alternative treatment option to NAC in the treatment of acetaminophen toxicity.

Keywords

Resveratrol, Acetaminophen, paracetamol, NAC, Toxicity

Project Number

selçuk üniversitesi deneysel tıp ve araştırma merkezi onay no:2015/77

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