Heme oxygenase-1 inhibitor tin-protoporphyrin improves liver regeneration after partial hepatectomy.

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Pibiri M, Leoni VP, Atzori L

Heme oxygenase-1 inhibitor tin-protoporphyrin improves liver regeneration after partial hepatectomy.

Life Sci. 2018 Jul 1;204:9-14. doi: 10.1016/j.lfs.2018.05.011. Epub 2018 May 5.

PubMed ID
29738777 [ View in PubMed
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Abstract

AIMS: This study investigates the effects of the heme oxygenase-1 (HO-1) inhibitor tin protoporphyrin IX (SnPP), on rat liver regeneration following 2/3 partial hepatectomy (PH) in order to clarify the controversial role of HO-1 in the regulation of cellular growth. MAIN METHODS: Male Wistar rats received a subcutaneous injection of either SnPP (10mumoles/kg body weight) or saline 12h before PH and 0, 12 and 24h after surgery. Rats were killed from 0.5 to 36h after PH. Bromodeoxyuridine (BrdU) incorporation was used to analyze cell proliferation. Immunohistochemistry, Western blot analysis and quantitative Real Time-PCR were used to assess molecular and cellular changes after PH. KEY FINDINGS: Data obtained have shown that administration of SnPP caused an increased entry of hepatocytes into S phase after PH, as demonstrated by labeling (L.I.) and mitotic (M.I.) indexes. Furthermore, enhanced cell cycle entry in PH-animals pre-treated with SnPP was associated with an earlier activation of IL-6 and transcription factors involved in liver regeneration, such as phospho-JNK and phospho-STAT3. SIGNIFICANCE: Summarizing, data here reported demonstrate that inhibition of HO-1 enhances rat liver regeneration after PH which is associated to a very rapid increase in the levels of inflammatory mediators such as IL-6, phopsho-JNK and phospho-STAT3, suggesting that HO-1 could act as a negative modulator of liver regeneration. Knowledge about the mechanisms of liver regeneration can be applied to clinical problems caused by delayed liver growth, and HO-1 repression may be a mechanism by which cells can faster proliferate in response to tissue damage.

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