Inflammatory Reaction In Liver Research Articles

Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli

Background Entamoeba nuttalli is an intestinal protozoan with pathogenic potential that can cause amoebic liver abscess. It is highly prevalent in wild and captive macaques. Recently, cysts were detected in a caretaker of nonhuman primates in a zoo, indicating that E. nuttalli may be a zoonotic pathogen. Therefore, it is important to evaluate the pathogenicity of E. nuttalli in detail and in comparison with that of E. histolytica. Methodology/Principal findings Trophozoites of E. nuttalli GY4 and E. histolytica SAW755 strains were inoculated into liver of hamsters. Expression levels of proinflammatory factors of hamsters and virulence factors from E. histolytica and E. nuttalli were compared between the two parasites. Inoculations with trophozoites of E. nuttalli resulted in an average necrotic area of 24% in liver tissue in 7 days, whereas this area produced by E. histolytica was nearly 50%. Along with the mild liver tissue damage induced by E. nuttalli, expression levels of proinflammatory factors (TNF-α, IL-6 and IL-1β) and amebic virulence protein genes (lectins, cysteine proteases and amoeba pores) in local tissues were lower with E. nuttalli in comparison with E. histolytica. In addition, M2 type macrophages were increased in E. nuttalli-induced amebic liver abscesses in the late stage of disease progression and lysate of E. nuttalli trophozoites induced higher arginase expression than E. histolytica in vitro. Conclusions/Significance The results show that differential secretion of amebic virulence proteins during E. nuttalli infection triggered lower levels of secretion of various cytokines and had an impact on polarization of macrophages towards a M1/M2 balance. However, regardless of the degree of macrophage polarization, there is unambiguous evidence of an intense acute inflammatory reaction in liver of hamsters after infection by both Entamoeba species.

Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli.

BackgroundEntamoeba nuttalli is an intestinal protozoan with pathogenic potential that can cause amebic liver abscess. It is highly prevalent in wild and captive macaques. Recently, cysts were detected in a caretaker of nonhuman primates in a zoo, indicating that E. nuttalli may be a zoonotic pathogen. Therefore, it is important to evaluate the pathogenicity of E. nuttalli in detail and in comparison with that of E. histolytica.Methodology/Principal findingsTrophozoites of E. nuttalli GY4 and E. histolytica SAW755 strains were inoculated into liver of hamsters. Expression levels of proinflammatory factors of hamsters and virulence factors from E. histolytica and E. nuttalli were compared between the two parasites. Inoculations with trophozoites of E. nuttalli resulted in an average necrotic area of 24% in liver tissue in 7 days, whereas this area produced by E. histolytica was nearly 50%. Along with the mild liver tissue damage induced by E. nuttalli, expression levels of proinflammatory factors (TNF-α, IL-6 and IL-1β) and amebic virulence protein genes (lectins, cysteine proteases and amoeba pores) in local tissues were lower with E. nuttalli in comparison with E. histolytica. In addition, M2 type macrophages were increased in E. nuttalli-induced amebic liver abscesses in the late stage of disease progression and lysate of E. nuttalli trophozoites induced higher arginase expression than E. histolytica in vitro.Conclusions/SignificanceThe results show that differential secretion of amebic virulence proteins during E. nuttalli infection triggered lower levels of secretion of various cytokines and had an impact on polarization of macrophages towards a M1/M2 balance. However, regardless of the degree of macrophage polarization, there is unambiguous evidence of an intense acute inflammatory reaction in liver of hamsters after infection by both Entamoeba species.

The effect of sodium butyrate on T helper cell 17 and the signal pathway of toll-like receptors 4 in autoimmune hepatitis

Objective To study the immunoregulatory effect of sodium butyrate (NaB) on T helper cell 17(Th17) and the effect on toll-like receptor 4(TLR4) signal pathway in autoimmune hepatitis (AIH). Methods Fifty male C57BL/6 mice (6 weeks of age) according to the random number table method divided into control group (n=10), AIH group (n=10), NaB group (n=10) and high roughage diet (HRD) group (n=10), and the other ten mice were used to extract hepatic sytosolic S-100. After the establishment of AIH model, mice in NaB group were given sodium butyrate 500 mg/(kg·d) by gavage and those in HRD group were fed with high-fiber stuff. After 3 weeks of treatment, all the mice were sacrificed. The pathological change was observed. The serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), IL-17A and TNF-α, the proportion of Th17 in spleen, the expression levels of TLR4 and myeloid differentiation factor 88 (MyD88) in liver were observed in each group. The tests of normality and homogeneity of variance were used to compare the means of each group. One-way analysis of variance and multiple comparative analyses were used in the statistical analysis. Results HE staining showed that inflammatory cell infiltration and hepatocyte necrosis were significantly reduced in mice treated with NaB and HRD compared to AIH group. Serum ALT levels in control group, AIH group, NaB group and HRD group were (24.833±2.229), (88.333±9.543), (27.167±3.189) and (29.833±6.113) U/L, respectively, while AST levels in each group were (97.00±14.953), (285.000±35.434), (139.500±38.976) and (127.167±28.687) U/L, respectively. The differences among groups were all statistically significant (F=156.49 and 44.118, respectively, both P<0.01). The proportion of Th17 in spleen and the expressions of the transcription factors retinoid-related orphan receptor gamma t in the spleen of the NaB group and HRD group were significantly lower than those of AIH group. The differences were statistically significantly (F=21.780 and 68.283, respectively, both P<0.05). The expressions of TLR4 and MyD88 in liver of AIH group were significantly higher than control group, but those were inhibited in NaB group and HRD group. The differences were statistically significantly (F=26.235 and 28.293, respectively, both P<0.01). The expressions of IL-17 and TNF-α in liver and serum decreased in NaB group and HRD group. Conclusion NaB exerts an immunoregulatory effect in AIH and improves inflammatory reaction in liver. Key words: Hepatitis, autoimmune; Sodium butyrate; High roughage diet; T helper cell 17; Toll-like receptor 4 signal pathway

Inhibitory effect of yellow myrobalan (Terminalia chebula) extract on fibrosis induced by carbon tetrachloride in rat liver

Ethyl acetate layer of methanol extract (TCE) of yellow myrobalan (Terminalia chebula) contains 2.4% of chebulic acid, a standard compound in TCE, which have a strong anti-oxidative effect and was reported in our previous study. Thirty-one male SD rats were randomly divided into 5 groups (normal control, CCl4 control, TCE control, CCl4+high dose TCE, and low dose TCE). Liver fibrosis was induced by i.p. injection of CCl4 and TCE were orally administrated. TCE decreased the up-regulated malondealdehyde value and increased the down-regulated ratio of GSH/GSSG content and activities of GRd, GPx, and GST compared to the CCl4 control group. Decreased dysfunction and inflammatory reaction in liver was confirmed by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, relative liver weight and infiltration of neutrophils. Also, TCE inhibited phenotype change of hepatic stellate cells (HSC) by reducing α-smooth muscle actin (α-SMA) gene expression and protein production. Inhibition of collagen 1A1 gene expression and protein production were also confirmed. From these results, TCE may be a useful material for preventing liver fibrosis.

Effect of acute ethanol treatment on biochemical and histopathological factors in rat liver in an experimental sepsis model

The aim of this study was to investigate the contribution of acute alcohol in sepsis-related liver damages using a Cecal Ligation and Puncture (CLP) model. Rats were divided into 7 groups (5 rats/group): control (saline-injected), sham-operated, CLP, ethanol (1.0 and 2.0g/kg b.w) and CLP+ethanol. The CLP+ethanol group received a single dose of ethanol following sepsis induction. Sepsis induction caused early changes in lipid peroxidation products in liver, whereas ethanol alone (2.0g/kg b.w) resulted in a significant increase (∼21%) in lipid peroxidation, which was further increased (∼57%) in CLP rats treated with alcohol. CLP operation and alcohol treatment exhibited additive effects on plasma catalase, liver glutathione and glutathione S-transferase (GST), which were primarily suppressed due to ethanol. Hepatic cytochrome P4501A1, which was elevated in CLP rats, was reversed in the CLP+ethanol group. Plasma tumor necrosis factor-α was markedly elevated (∼85%) in septic rats, but was unaffected in septic rats having received ethanol. Histopathological observations revealed that inflammatory reactions in liver in response to CLP operation are not intensified by ethanol administration. On the basis of biochemical and histopathological results, it can be concluded that acute ethanol treatment is responsible for early changes in oxidative stress, which may lead to polymicrobial sepsis-related organ damage.

Leishmania (Leishmania) amazonensis: Experimental cutaneous leishmaniasis associated with systemic amyloidosis in mice

We infected Swiss and C57BL/6 female mice in the left hind footpad with 104Leishmania (L.) amazonensis promastigotes in stationary phase. The macroscopic examination showed a nodular non-ulcerated lesion at the site of inoculation and hepatic and spleenic enlargement. Histopathologically, the primary lesion showed an extensive liquefactive necrosis and inflammatory infiltrate, mainly consisting of macrophages filled with amastigotes, and rare lymphocytes. The inflammatory reaction in liver, spleen and kidney showed amyloid deposits. Additionally, C57BL/6 had accentuated amyloidosis in both ovarian cortical and medullar region and inflammatory infiltrates in the pancreas and adrenal gland.

Some Clinico and Histopathological Changes in Female Goats Experimentally Exposed to Dioxin

Female Baladi goats were used for investigating the toxicological effects of dioxin. Each animal in the treated group was given an oral dose of 4 mL of stock standard solution of dioxin (labelled and native congeners) diluted in 5 mL distilled water (1/3 of LD50) for three times with 2 days interval and slaughtered 16 days post treatment. Blood and tissue samples were taken and subjected for haemogram, biochemical and pathological studies as well as for determination of dioxin residues. Results revealed that exposure of female goats to dioxin induced anemia, leucocytopenia, neutropenia and eosinophilia with non significant increases in activities of serum ALT and AST as compared with untreated group. Meanwhile, activity of ALP and BUN concentration were significantly increased. Histopathological examination showed degenerative and necrotic changes associated with inflammatory reaction in liver and kidney, in addition to cystic glandular hyperplasia and adenomyosis in uterus. In ovarian tissue, marked decrease ofpreantral follicles together with cystic atretic follicle were noticed. The average percentage residues ofpg WHO-TEQ values for dioxins (PCDDs and PCDFs) in liver, kidney, mammary gland, uterus and milk after oral dose were 0.013, 0.0012, 0.0012, 0.009 and 0.0012%, respectively. It was concluded that oral exposure to dioxin in female goats induced adverse effects on liver and kidney. Dioxins had estrogenic like effect as indicated by uterine and ovarian histopathological changes.

Dietary isoflavones suppress endotoxin-induced inflammatory reaction in liver and intestine

Dietary isoflavone intake has been linked to cancer prevention and their anti-inflammation activity was examined. Intraperitoneal lipopolysaccharide (LPS) injection in mice led to a decrease in the liver antioxidant glutathione level but this decrease was prevented in mice fed with an isoflavone-containing diet. Similarly, isoflavone diet prevented the inflammation-associated induction of metallothionein (MT) in the intestine; and the induction of manganese superoxide dismutase (Mn-SOD) in the liver. Results from the intestinal cell studies suggest that isoflavones suppress the intestinal response to inflammation by modulating the action of pro-inflammatory cytokine, IL-6. IL-6 secretion and the STAT3 (signal transducer and activator of transcription protein 3) nuclear translocation in response to IL-6 were both decreased by genistein.

Autoantibodies to cryptic epitopes elicited by infection with lactate dehydrogenase-elevating virus.

Lactate dehydrogenase-elevating virus (LDV) produces a permanent infection in mice with a B-lymphocyte polyclonal activation leading to hypergammaglobulinaemia. Since LDV specifically suppressed antibodies to native epitopes in CBA/Ht, but not BALB/c, mice immunized against a protein antigen, we explored the relationship between such a change in antibody specificity and the expression of autoantibodies under the influence of LDV. Again in CBA/Ht, but not BALB/c, mice we observed another effect of LDV: the sera from infected CBA/Ht mice were found by enzyme-linked immunosorbant assay to contain antibodies to various mouse tissue extracts. Immunoblots revealed a large spectrum of autoantigens that differed markedly between animals. Western-blot competition experiments showed that the protein autoantigens had to be denatured to react with most of the autoantibodies. Despite the presence of these autoantibodies directed to cryptic epitopes, no specific tissue lesions could be ascribed to the autoimmune response elicited by LDV infection, since both mouse strains showed mild inflammatory reactions in liver and kidney.