Promoter function of carrageenan on development of colonic tumors induced by 1,2-dimethylhydrazine in rats

In order to understand the function of carrageenan, an indigestible polysaccharide, as a promoter of colonic tumors induced by 1,2-dimethylhydrazine (DMH), molecular weight distribution of fecal carrageenan and amounts of fecal bile acids in rats given carrageenan and DMH treatment were examined. Gel filtration pattern on Sephacryl S-300 of fecal carrageenan was very similar to that of feeding carrageenan, and carrageenan ingested was quantitatively excreted in feces. Hexafluoroisopropyl ester-trifluoroacetyl derivatives of fecal bile acids were analyzed by gas chromatography on QF-1. Although there was a decreased concentration of deoxycholic acid and total bile acids in carrageenan-fed rats compared to control rats, no difference in the daily output was found because carrageenan ingestion increases fecal output. Significant increased concentration and daily output of lithocholic acid, a tumor-promoter, by feeding carrageenan were found. Thus, it was suggested that the promoting effect of carrageenan on colon tumorigenesis by DMH may be mediated by increased excretion of lithocholic acid and may not participate in degradation of carrageenan ingested.     

Role of lymphoid cells in age-related change of susceptibility to Friend leukemia virus-induced leukemia

Susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the C3H/He (C3H)-->C57BL/6 (B6) radiation bone marrow chimeras of various age groups, and the effect of aging of host mice on the susceptibility was determined. The bone marrow chimera system provided the various age of FLV-resistant host mice (B6) possessing the same age of FLV-susceptible target cells from C3H mice. Using this system, we could determine the aging effect on the host resistancy against FLV without an influence of the aging effect on target cells. First, the young C3H-->young B6 chimeras and young C3H-->old B6 chimeras were compared. The young-->old chimeras were more susceptible to FLV-induced acute disease than the young-->young chimeras. The spleen CD4+ as well as CD8+ T cells were reduced in young-->old chimeras compared with young-->young chimeras. Similarly, the old C3H-->old B6 chimeras were more susceptible than old-->young chimeras and revealed the lower CD4+ T cell ratio in the spleen. Discussion was made on the possible implication of these findings on the role of T cells in age-related change of resistance to FLV-induced leukemogenesis.     

Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells

AIM To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning.METHODS The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion.To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase,gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of o~gen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium.RESULTS Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which was reversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning.CONCLUSION H2O2 preconditioning protects hepatocytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning.     

Thrombocytopenia is more severe in patients with advanced chronic hepatitis C than B with the same grade of liver stiffness and splenomegaly

Background and aim

The mechanism responsible for thrombocytopenia in chronic liver diseases (CLD) is not yet fully understood. The prevalence of thrombocytopenia has been reported to be higher in patients with hepatitis C virus-related hepatocellular carcinoma (CLD-C) than in those with hepatitis B virus-related hepatocellular carcinoma (CDC-B). We have examined the potential difference in thrombocytopenia between patients with CLD-B and those with CLD-C in terms of liver fibrosis adjustment and splenomegaly.

Methods

The study cohort consisted of 102 patients with CLD-B and 143 patients with CLD-C were enrolled. Liver stiffness, which is reported to be well correlated with the degree of liver fibrosis, was measured by transient elastography.

Results

The analysis of covariance with liver stiffness as a covariate revealed that the platelet count was lower in CLD-C patients than in CLD-B patients. Following stratification for liver stiffness, thrombocytopenia was found to be more severe in CLD-C patients than CLD-B patients with advanced liver stiffness, whereas the degree of splenomegaly was not significantly different. The plasma thrombopoietin level was not different between CLD-B and CLD-C patients with advanced liver stiffness, and the immature platelet number was lower in CLD-C patients despite thrombocytopenia being more severe in these patients.

Conclusions

CLD-C patients with advanced liver stiffness presented with more severe levels of thrombocytopenia than CLD-B patients even with the same grade of splenomegaly. Impaired platelet production rather than enhanced platelet destruction may underlie the mechanism responsible for thrombocytopenia in patients with CLD.