Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model

Ischemia–reperfusion is defined as cellular damage after the reperfusion of ischemic tissue, and it is likely to occur in relation to various diseases and surgical procedures. The purpose of this study was to evaluate the capability of atorvastatin to prevent oxidative damage and modulate the releas...

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Main Authors: Walter A Trujillo-Rangel, Araceli Castillo-Romero, Sylvia E Totsuka-Sutto, Simón Q Rodríguez-Lara, Teresa A García-Cobián, Tannia I Campos-Bayardo, Ernesto G Cardona-Muñoz, Leonel García-Benavides
Format: Article
Language:English
Published: SAGE Publishing 2018-12-01
Series:European Journal of Inflammation
Online Access:https://doi.org/10.1177/2058739218812664
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author Walter A Trujillo-Rangel
Araceli Castillo-Romero
Sylvia E Totsuka-Sutto
Simón Q Rodríguez-Lara
Teresa A García-Cobián
Tannia I Campos-Bayardo
Ernesto G Cardona-Muñoz
Leonel García-Benavides
author_facet Walter A Trujillo-Rangel
Araceli Castillo-Romero
Sylvia E Totsuka-Sutto
Simón Q Rodríguez-Lara
Teresa A García-Cobián
Tannia I Campos-Bayardo
Ernesto G Cardona-Muñoz
Leonel García-Benavides
author_sort Walter A Trujillo-Rangel
collection DOAJ
description Ischemia–reperfusion is defined as cellular damage after the reperfusion of ischemic tissue, and it is likely to occur in relation to various diseases and surgical procedures. The purpose of this study was to evaluate the capability of atorvastatin to prevent oxidative damage and modulate the release of proinflammatory cytokines in rat hindlimb during ischemia–reperfusion injury. The animals were divided into 4 groups (ischemia–reperfusion + vehicle, ischemia–reperfusion + atorvastatin, sham, and healthy controls) with 15 rats per group. The animals were exposed to ischemia for 6 h, followed by 24 h, 7 days, and 14 days of reperfusion. Atorvastatin was administered by gavage 14 days before ischemia–reperfusion induction. We then measured the serum concentrations and mRNA transcript levels of TNF-α, IL-1β, IL-6, IL-10, SOD2 , and CAT . Hematoxylin and eosin stain were performed for histological analyses. Animals subjected to ischemia–reperfusion showed increased serum and transcript levels of TNF-α, IL-1β, IL-6 , and IL-10 expressions with a concurrent increase in mRNA transcripts levels compared with sham and healthy controls. Groups treated with atorvastatin showed a significant CAT increase in the first 24 h, but CAT levels decreased at 7 and 14 days. SOD2 enzyme increased in serum without significant changes in mRNA expression. Histological analysis showed inflammatory infiltrate, microhemorrhages, and distortion of the tissue architecture in the first 7 days. At 14 days, the tissue showed loss and damage to myocytes. However, animals treated with atorvastatin showed few histological changes and a decrease in inflammatory cytokines. No significant changes in NO 2 , NO 3 , or 8-OHdG were observed. Atorvastatin showed a protective effect on the inflammation and tissue damage induced by ischemia–reperfusion in the hindlimb. The antioxidant effect of atorvastatin in the hindlimb is already unclear, and further research is needed to elucidate the molecular mechanism of this drug in the extremities.
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spelling doaj.art-a8910d5887974f46bf1c40e27a39d3f82022-12-21T20:37:27ZengSAGE PublishingEuropean Journal of Inflammation2058-73922018-12-011610.1177/2058739218812664Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion modelWalter A Trujillo-Rangel0Araceli Castillo-Romero1Sylvia E Totsuka-Sutto2Simón Q Rodríguez-Lara3Teresa A García-Cobián4Tannia I Campos-Bayardo5Ernesto G Cardona-Muñoz6Leonel García-Benavides7Departamento de Fisiología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Microbiología y Patología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Fisiología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Fisiología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Fisiología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Fisiología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Fisiología, Universidad de Guadalajara, Guadalajara, MéxicoDepartamento de Ciencias Biomédicas, CUTonalá, Universidad de Guadalajara, Tonalá, MéxicoIschemia–reperfusion is defined as cellular damage after the reperfusion of ischemic tissue, and it is likely to occur in relation to various diseases and surgical procedures. The purpose of this study was to evaluate the capability of atorvastatin to prevent oxidative damage and modulate the release of proinflammatory cytokines in rat hindlimb during ischemia–reperfusion injury. The animals were divided into 4 groups (ischemia–reperfusion + vehicle, ischemia–reperfusion + atorvastatin, sham, and healthy controls) with 15 rats per group. The animals were exposed to ischemia for 6 h, followed by 24 h, 7 days, and 14 days of reperfusion. Atorvastatin was administered by gavage 14 days before ischemia–reperfusion induction. We then measured the serum concentrations and mRNA transcript levels of TNF-α, IL-1β, IL-6, IL-10, SOD2 , and CAT . Hematoxylin and eosin stain were performed for histological analyses. Animals subjected to ischemia–reperfusion showed increased serum and transcript levels of TNF-α, IL-1β, IL-6 , and IL-10 expressions with a concurrent increase in mRNA transcripts levels compared with sham and healthy controls. Groups treated with atorvastatin showed a significant CAT increase in the first 24 h, but CAT levels decreased at 7 and 14 days. SOD2 enzyme increased in serum without significant changes in mRNA expression. Histological analysis showed inflammatory infiltrate, microhemorrhages, and distortion of the tissue architecture in the first 7 days. At 14 days, the tissue showed loss and damage to myocytes. However, animals treated with atorvastatin showed few histological changes and a decrease in inflammatory cytokines. No significant changes in NO 2 , NO 3 , or 8-OHdG were observed. Atorvastatin showed a protective effect on the inflammation and tissue damage induced by ischemia–reperfusion in the hindlimb. The antioxidant effect of atorvastatin in the hindlimb is already unclear, and further research is needed to elucidate the molecular mechanism of this drug in the extremities.https://doi.org/10.1177/2058739218812664
spellingShingle Walter A Trujillo-Rangel
Araceli Castillo-Romero
Sylvia E Totsuka-Sutto
Simón Q Rodríguez-Lara
Teresa A García-Cobián
Tannia I Campos-Bayardo
Ernesto G Cardona-Muñoz
Leonel García-Benavides
Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model
European Journal of Inflammation
title Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model
title_full Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model
title_fullStr Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model
title_full_unstemmed Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model
title_short Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model
title_sort effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia reperfusion model
url https://doi.org/10.1177/2058739218812664
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