Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency

Hdl Handle:
http://hdl.handle.net/11285/622454
Title:
Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency
Authors:
Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma; Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma
Issue Date:
04/05/2017
Abstract:
Abstract Background Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl4)-induced liver damage compared to healthy controls (Wt Igf +/+). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/−). Methods Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+) were included in the protocol: untreated controls (Wt). Controls that received CCl4 (Wt + CCl4) and Wt + CCl4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl4 + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/−) groups were studied: untreated Hz, Hz + CCl4, and Hz + CCl4 + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. Results An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl4 + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl4. Moreover, there was a correlation between MDA levels and the histological damage score (Pearson’s r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. Conclusions IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series (healthy and IGF-1-deficient mice) with acute liver damage, suggesting that low doses of IGF-1, in acute liver damage, could be a feasible therapeutic option.
Type:
Journal Article
Appears in Collections:
Artículos de Revistas

Full metadata record

DC FieldValue Language
dc.contributor.authorMorales-Garza, Luis A-
dc.contributor.authorPuche, Juan E-
dc.contributor.authorAguirre, Gabriel A-
dc.contributor.authorMuñoz, Úrsula-
dc.contributor.authorGarcía-Magariño, Mariano-
dc.contributor.authorDe la Garza, Rocío G-
dc.contributor.authorCastilla-Cortazar, Inma-
dc.contributor.authorMorales-Garza, Luis Aes
dc.contributor.authorPuche, Juan Ees
dc.contributor.authorAguirre, Gabriel Aes
dc.contributor.authorMuñoz, Úrsulaes
dc.contributor.authorGarcía-Magariño, Marianoes
dc.contributor.authorDe la Garza, Rocío Ges
dc.contributor.authorCastilla-Cortazar, Inmaes
dc.date.accessioned2017-05-05T21:20:12Z-
dc.date.available2017-05-05T21:20:12Z-
dc.date.issued04/05/2017-
dc.identifier.citationJournal of Translational Medicine. 2017 May 04;15(1):96-
dc.identifier.urihttp://dx.doi.org/10.1186/s12967-017-1198-4-
dc.identifier.urihttp://hdl.handle.net/11285/622454-
dc.description.abstractAbstract Background Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl4)-induced liver damage compared to healthy controls (Wt Igf +/+). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/−). Methods Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+) were included in the protocol: untreated controls (Wt). Controls that received CCl4 (Wt + CCl4) and Wt + CCl4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl4 + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/−) groups were studied: untreated Hz, Hz + CCl4, and Hz + CCl4 + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. Results An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl4 + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl4. Moreover, there was a correlation between MDA levels and the histological damage score (Pearson’s r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. Conclusions IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series (healthy and IGF-1-deficient mice) with acute liver damage, suggesting that low doses of IGF-1, in acute liver damage, could be a feasible therapeutic option.-
dc.rightsOpen Access-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleExperimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderThe Author(s)-
dc.date.updated2017-05-05T14:00:09Z-
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