Lactobacillus casei Zhang (LcZ) has been recently isolated from the traditional Mongolian beverage koumiss and has a set of favorable probiotic properties, including aciduricity, bile resistance and ability to colonize the gastrointestinal tract. We have previously reported the anti-oxidative properties of LcZ in the hyperlipidemic rats. In this study, the hepatoprotective effects of LcZ against lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced liver injury were investigated. We found that pretreatment with LcZ significantly improved survival of rats challenged with LPS/D-GalN. In addition, pretreatment with LcZ significantly decreased alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in LPS/D-GalN-challenged rats, which were accompanied by diminished liver injuries, reduced malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in liver homogenates. Pretreatment with LcZ also markedly reduced LPS/D-GalN-induced production of hepatic nitric oxide (NO), activation of inducible nitric oxide synthase (iNOS) and expression of tumor necrosis factor-α (TNF-α). Furthermore, hepatic toll-like receptor 4 (TLR4) mRNA and protein levels, the phosphorylation of I-κB and translocation of nuclear factor κB (NF-κB) were significantly down-regulated by pretreatment with LcZ. These results suggest that pretreatment with LcZ protects against LPS/D-GalN-induced liver injury in rats via its anti-oxidative and anti-inflammatory capacities. The hepatoprotective effects of LcZ are associated with an inhibition of TLR4 expression and TLR4 signaling.
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