Cargando…

Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats

INTRODUCTION: The study aimed at investigating the hepatic effect of direct acting anti-hepatitis C virus drugs (DAAs), sofosbuvir (Sof) and daclatasvir (Dac), in thioacetamide (TAA)-induced liver injury in rats. MATERIAL AND METHODS: Animals were allocated to 7 groups: a normal control group, a TAA...

Descripción completa

Detalles Bibliográficos
Autores principales: Ibrahim, Mohamed A., Abdel-Aziz, Asmaa, El-Sheikh, Azza, Kamel, Maha, Khalil, Al-Zahraa, Abdelhaleem, Hisham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185925/
https://www.ncbi.nlm.nih.gov/pubmed/30324142
http://dx.doi.org/10.5114/ceh.2018.78121
_version_ 1783362770003034112
author Ibrahim, Mohamed A.
Abdel-Aziz, Asmaa
El-Sheikh, Azza
Kamel, Maha
Khalil, Al-Zahraa
Abdelhaleem, Hisham
author_facet Ibrahim, Mohamed A.
Abdel-Aziz, Asmaa
El-Sheikh, Azza
Kamel, Maha
Khalil, Al-Zahraa
Abdelhaleem, Hisham
author_sort Ibrahim, Mohamed A.
collection PubMed
description INTRODUCTION: The study aimed at investigating the hepatic effect of direct acting anti-hepatitis C virus drugs (DAAs), sofosbuvir (Sof) and daclatasvir (Dac), in thioacetamide (TAA)-induced liver injury in rats. MATERIAL AND METHODS: Animals were allocated to 7 groups: a normal control group, a TAA group (receiving TAA 50 mg/kg, i.p. twice weekly), two TAA groups receiving either a low or a high dose of Sof (Sof-L and Sof-H; 41.1 mg/kg and 82.2 mg/kg, respectively), two TAA groups receiving either a low or a high dose of Dac (Dac-L and Dac-H; 6.2 mg/kg and 12.4 mg/kg, respectively), and a TAA group receiving both Sof-L and Dac-L. RESULTS: After 6 weeks, TAA significantly elevated the serum activities of liver enzymes, along with histopathological evidence of liver injury. These findings were associated with a significant increase in a fibrotic marker (tissue inhibitor metalloproteinase-1 – TIMP-1), proinflammatory cytokine (tumor necrosis factor alpha – TNF-α), and oxidative stress parameters (malondialdehyde [MDA] content, and superoxide dismutase [SOD] and catalase activities) in hepatic tissue. TAA rats treated with Sof-L, Dac-L, Dac-H and a combination of Sof-L plus Dac-L showed significant amelioration of TAA-induced liver injury. Their effects were accompanied by a significant reduction in TIMP-1, TNF-α and oxidative stress parameters in hepatic tissue. Interestingly, Sof-H caused no improvement in TAA-induced hepatic injury. CONCLUSIONS: The hepatic effects of Sof and Dac in TAA-induced liver injury appeared to be mediated by anti-oxidant effects, and inhibition of TNF-α and TIMP-1.
format Online
Article
Text
id pubmed-6185925
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Termedia Publishing House
record_format MEDLINE/PubMed
spelling pubmed-61859252018-10-15 Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats Ibrahim, Mohamed A. Abdel-Aziz, Asmaa El-Sheikh, Azza Kamel, Maha Khalil, Al-Zahraa Abdelhaleem, Hisham Clin Exp Hepatol Original Paper INTRODUCTION: The study aimed at investigating the hepatic effect of direct acting anti-hepatitis C virus drugs (DAAs), sofosbuvir (Sof) and daclatasvir (Dac), in thioacetamide (TAA)-induced liver injury in rats. MATERIAL AND METHODS: Animals were allocated to 7 groups: a normal control group, a TAA group (receiving TAA 50 mg/kg, i.p. twice weekly), two TAA groups receiving either a low or a high dose of Sof (Sof-L and Sof-H; 41.1 mg/kg and 82.2 mg/kg, respectively), two TAA groups receiving either a low or a high dose of Dac (Dac-L and Dac-H; 6.2 mg/kg and 12.4 mg/kg, respectively), and a TAA group receiving both Sof-L and Dac-L. RESULTS: After 6 weeks, TAA significantly elevated the serum activities of liver enzymes, along with histopathological evidence of liver injury. These findings were associated with a significant increase in a fibrotic marker (tissue inhibitor metalloproteinase-1 – TIMP-1), proinflammatory cytokine (tumor necrosis factor alpha – TNF-α), and oxidative stress parameters (malondialdehyde [MDA] content, and superoxide dismutase [SOD] and catalase activities) in hepatic tissue. TAA rats treated with Sof-L, Dac-L, Dac-H and a combination of Sof-L plus Dac-L showed significant amelioration of TAA-induced liver injury. Their effects were accompanied by a significant reduction in TIMP-1, TNF-α and oxidative stress parameters in hepatic tissue. Interestingly, Sof-H caused no improvement in TAA-induced hepatic injury. CONCLUSIONS: The hepatic effects of Sof and Dac in TAA-induced liver injury appeared to be mediated by anti-oxidant effects, and inhibition of TNF-α and TIMP-1. Termedia Publishing House 2018-09-10 2018-09 /pmc/articles/PMC6185925/ /pubmed/30324142 http://dx.doi.org/10.5114/ceh.2018.78121 Text en Copyright: © 2018 Clinical and Experimental Hepatology http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Original Paper
Ibrahim, Mohamed A.
Abdel-Aziz, Asmaa
El-Sheikh, Azza
Kamel, Maha
Khalil, Al-Zahraa
Abdelhaleem, Hisham
Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
title Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
title_full Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
title_fullStr Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
title_full_unstemmed Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
title_short Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
title_sort hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185925/
https://www.ncbi.nlm.nih.gov/pubmed/30324142
http://dx.doi.org/10.5114/ceh.2018.78121
work_keys_str_mv AT ibrahimmohameda hepaticeffectofsofosbuviranddaclatasvirinthioacetamideinducedliverinjuryinrats
AT abdelazizasmaa hepaticeffectofsofosbuviranddaclatasvirinthioacetamideinducedliverinjuryinrats
AT elsheikhazza hepaticeffectofsofosbuviranddaclatasvirinthioacetamideinducedliverinjuryinrats
AT kamelmaha hepaticeffectofsofosbuviranddaclatasvirinthioacetamideinducedliverinjuryinrats
AT khalilalzahraa hepaticeffectofsofosbuviranddaclatasvirinthioacetamideinducedliverinjuryinrats
AT abdelhaleemhisham hepaticeffectofsofosbuviranddaclatasvirinthioacetamideinducedliverinjuryinrats