S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats

Hepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the...

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Main Authors: Sergio Valdés, Sergio D. Paredes, Carmen García Carreras, Pilar Zuluaga, Lisa Rancan, Beatriz Linillos-Pradillo, Javier Arias-Díaz, Elena Vara
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/12/8/1539
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author Sergio Valdés
Sergio D. Paredes
Carmen García Carreras
Pilar Zuluaga
Lisa Rancan
Beatriz Linillos-Pradillo
Javier Arias-Díaz
Elena Vara
author_facet Sergio Valdés
Sergio D. Paredes
Carmen García Carreras
Pilar Zuluaga
Lisa Rancan
Beatriz Linillos-Pradillo
Javier Arias-Díaz
Elena Vara
author_sort Sergio Valdés
collection DOAJ
description Hepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-α, IL-1β, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-α, IL-1β, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI.
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spelling doaj.art-b7f46cc069a3415c973be4cdc365b41d2023-11-19T00:01:27ZengMDPI AGAntioxidants2076-39212023-07-01128153910.3390/antiox12081539S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar RatsSergio Valdés0Sergio D. Paredes1Carmen García Carreras2Pilar Zuluaga3Lisa Rancan4Beatriz Linillos-Pradillo5Javier Arias-Díaz6Elena Vara7Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartment of Physiology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartmental Unit of Biostatistics—Department of Statistics and Operations Research, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartment of Surgery, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s/n, 28040 Madrid, SpainHepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-α, IL-1β, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-α, IL-1β, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI.https://www.mdpi.com/2076-3921/12/8/1539S-adenosylmethionineischemia-reperfusionlivercytokineendotoxinlipid hydroperoxide
spellingShingle Sergio Valdés
Sergio D. Paredes
Carmen García Carreras
Pilar Zuluaga
Lisa Rancan
Beatriz Linillos-Pradillo
Javier Arias-Díaz
Elena Vara
S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats
Antioxidants
S-adenosylmethionine
ischemia-reperfusion
liver
cytokine
endotoxin
lipid hydroperoxide
title S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats
title_full S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats
title_fullStr S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats
title_full_unstemmed S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats
title_short S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats
title_sort s adenosylmethionine decreases bacterial translocation proinflammatory cytokines oxidative stress and apoptosis markers in hepatic ischemia reperfusion injury in wistar rats
topic S-adenosylmethionine
ischemia-reperfusion
liver
cytokine
endotoxin
lipid hydroperoxide
url https://www.mdpi.com/2076-3921/12/8/1539
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