These results indicate that the protective effect of DFO against APAP-induced liver injury may be attributable not to changes in APAP metabolism but to the chelation of iron, which can catalyze the generation of active oxygen species, in hepatocytes.

: We examined the effect of cyclosporin A (CsA) on the pathogenesis of acute experimental liver injury in rats induced by injection of heat‐killed Propionibacterium acnes (P. acnes) and subsequent injection of lipopolysaccharide (LPS). Pretreatment with CsA significantly reduced serum alanine aminotransferase (ALT), serum tumor necrosis factor‐α (TNF‐α) production, without changing the TNF‐α mRNA level in the liver, and plasma interferon‐γ (IFN‐γ), following LPS injection in this model. Twenty‐four‐hour mortality was also markedly improved, from 100% in the P. acnes plus LPS group to 0% in the CsA‐pretreated group. Although direct addition of CsA to isolated hepatic macrophages from P. acnes‐pretreated rats did not prevent the production of TNF‐α and active oxygen species, isolated hepatic macrophages from P. acnes plus CsA‐pretreated rats significantly reduced their production in response to the addition of LPS. These results suggest that CsA protects against P. acnes plus LPS‐induced acute liver injury, not by direct inhibition of hepatic macrophage activation, but by indirect prevention of hepatic macrophage activation, presumably related to the reduction in plasma IFN‐γ levels.

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