Experimental approach to IGF-1 therapy in CCl(4)-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency

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 (CCl(4))-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 CCl(4) (Wt + CCl(4)) and Wt + CCl(4) were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl(4) + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 (+/−)) groups were studied: untreated Hz, Hz + CCl(4), and Hz + CCl(4) + 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 + CCl(4) + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl(4). 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1198-4) contains supplementary material, which is available to authorized users.