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

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 ^+/-).

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.

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.

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.