Liver Injury In Lipopolysaccharide Research Articles

Resveratrol alleviates lipopolysaccharide-induced liver injury by inducing SIRT1/P62-mediated mitophagy in gibel carp (Carassius gibelio).

Resveratrol (RES) is a polyphenol organic compound with antioxidant and anti-inflammatory properties. This study aimed to determine whether and how RES can alleviate liver injury in lipopolysaccharide (LPS)-induced gibel carp. Gibel carp were fed a diet with or without RES and were cultured for 8 weeks, followed by LPS injection. The results suggested that RES attenuated the resulting oxidative stress and inflammation by activating the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway, as confirmed by changes in oxidative stress, inflammation-related gene expression, and antioxidant enzyme activity. Furthermore, RES cleared damaged mitochondria and enhanced mitochondrial biogenesis to mitigate reactive oxygen species (ROS) accumulation by upregulating the SIRT1/PGC-1α and PINK1/Parkin pathways and reducing p62 expression. Overall, RES alleviated LPS-induced oxidative stress and inflammation in gibel carp through mitochondria-related mechanisms.

Soshiho-tang protects LPS-induced acute liver injury by attenuating inflammatory response.

Soshiho-tang (SSHT) has traditionally been used to treat gastrointestinal disorders. In this experiment, we investigated the protective effect of SSHT on inflammatory liver injury in lipopolysaccharide (LPS)-sensitized mice. Male C57BL/6J mice aged 6weeks were randomly placed in 6 groups (n = 5): normal mice (CTR), LPS-sensitized mice (LPS), LPS-sensitized mice treated with dexamethasone (DEX) and LPS-sensitized mice treated with 0.05, 0.55, and 5.55g/kg of SSHT (SSHT 0.05, SSHT 0.55, and SSHT 5.55). Various doses of SSHT was given once a day for 7days. After 2h of LPS injection, the liver tissue was collected. SSHT pretreatment recovered hemorrhage of liver tissues in LPS-induced acute liver injury. The expressions of MAP Kinase, NF-κB, IκBα, p-IκBα, COX-2, and iNOS protein levels were markedly decreased by SSHT-treated liver tissues. Additionally, SSHT pretreatment significantly regulated the expressions of MCP-1, TNF-α, and IL-6 cytokines. These results suggest the potential of SSHT on the protection of acute liver injury.

Which one is more effective for the treatment of rat sepsis model: thalidomide or etanercept?

We aimed to investigate the protective effect of selected treatment agents on liver injury in lipopolysaccharide (LPS)-induced rat sepsis model. The sepsis includes complex inflammatory responses between a microbial pathogen and the host immune system, and leads to organ failure and also death. This study was performed with 29 male Wistar Albino rats. Rats were divided randomly into five groups: Sham group, LPS-treated sepsis group, LPS+thalidomide treated group, LPS+etanercept treated group and LPS+thalidomide+etanercept treated group, respectively. Liver tissue tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels were determined by enzyme-linked immuno-sorbent assay (ELISA) method. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was performed using western blot analysis. The levels of tissue TNF-α, IL-1β and IL-6 were found statistically significantly higher in sepsis group than in the sham group. TNF-α levels were found statistically significantly decreased in LPS+etanercept and LPS+thalidomide+etanercept treated groups when compared with LPS group (p < 0.05). For IL-1β and IL-6 levels a statistically significant decline was observed in the LPS+thalidomide and LPS+etanercept treated groups compared to the LPS group (p < 0.05). Expression of NF-κB protein in liver tissue was significantly elevated in the LPS group compared to sham group (p < 0.001). In treatment groups, a marked decrease was observed in NF-κB protein expression. The results of this investigation suggested that etanercept and thalidomide administration may have a beneficial effect on LPS-induced sepsis. So, the present study may have significant clinical relevance, but clinical trials are needed to confirm these results (Tab. 1, Fig. 1, Ref. 36).

CYP3A induction aggravates endotoxemic liver injury via reactive oxygen species in male rats

We carried out this experiment to evaluate the relationship between isoforms of cytochrome P450 (P450) and liver injury in lipopolysaccharide (LPS)-induced endotoxemic rats. Male rats were intraperitoneally administered phenobarbital (PB), a P450 inducer, for 3 days, and 1 day later, they were intravenously given LPS. PB significantly increased P450 levels (200% of control levels) and the activities (300–400% of control) of the specific isoforms (CYP), CYP3A2 and CYP2B1, in male rats. Plasma AST and ALT increased slightly more in PB-treated rats than in PB-nontreated (control) rats with LPS treatment. Furthermore, either troleandomycin or ketoconazole, specific CYP3A inhibitors, significantly inhibited LPS-induced liver injury in control and PB-treated male rats. To evaluate the oxidative stress in LPS-treated rats, in situ superoxide radical detection using dihydroethidium (DHE), hydroxy-2-nonenal (HNE)-modified proteins in liver microsomes and 8-hydroxydeoxyguanosine (8-OHdG) in liver nuclei were measured in control and PB-treated rats. DHE signal intensity, levels of HNE-modified proteins, and 8-OHdG increased significantly in PB-treated rats. LPS further increased DHE intensity, HNE-modified proteins, and 8-OHdG levels in normal and PB-treated groups. CYP3A inhibitors also inhibited the increases in these items. Our results indicate that the induction or preservation of CYP isoforms further promotes LPS-induced liver injury through mechanisms related to oxidative stress. In particular, CYP3A2 of P450 isoforms made an important contribution to this LPS-induced liver injury.

Lead enhances lipopolysaccharide and tumor necrosis factor liver injury.

Lead markedly augments the lethality of endotoxin lipopolysaccharide (LPS) in rats. In this model of LPS toxicity, the liver is severely injured. Much of the tissue injury produced by LPS is thought to be mediated by the cytokine tumor necrosis factor (TNF). Tumor necrosis factor recently has been speculated to be a mediator of several models of liver injury such as that produced by galactosamine. To investigate the possible role of TNF in the lead-enhanced LPS toxicity model, we administered doses of lead acetate (15 mg/kg), LPS (100 micrograms/kg), or TNF (6.25 x 10(6) U/kg) that produced minimal changes in liver enzymes. However, when lead was administered simultaneously with either LPS or TNF, serum aspartate transaminase, alanine transaminase, alkaline phosphatase, glutamyl transpeptidase, and plasma triglyceride levels were markedly increased. Lead + LPS treatment increased both peak serum TNF concentrations and TNF "area under the curve" as compared with LPS alone. We conclude that lead not only enhances LPS lethality but also LPS liver injury. Furthermore, lead enhances TNF liver injury and increases LPS-stimulated serum TNF levels. These data suggest that the lead-enhanced LPS model offers a system for studying TNF-induced liver injury.