Protective Effect of Chlorogenic Acid against Carbon Tetrachloride-induced Acute Liver Damage in Rats

Objective To evaluate the protective effect of chlorogenic acid （CGA） on carbon tetrachloride （CCh）-induced liver injury of rats. Methods The anti-oxidative activity of CGA was investigated with several established in vitro systems. The hepatoprotective activity of CGA against CCI4-induced acute liver injury in eats was studied. The levels of alanine aminotranferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, and total bilirubin （TB） were measured. The histopathological examination was carried out to supplement the biochemical results. Results CGA possessed strong anti-oxidative ability in vitro. The CCh-induced liver toxicity experiment showed that the rats pretreated with CGA （300 or 500 mg/kg） had lower levels of ALT, AST, ALP, and TB than those of the CCI4-treated group. These data were supplemented with histopathological examination of rat liver sections. CGA did not show any mortality at the dose up to 5000 mg/kg. Conclusion CGAcould protect the liver againstCCI4-induced oxidative damage in rats, and the possible mechanism of the activity may be due to its free radical-scavenging and anti-oxidative activity.

Reabsorption of iron into acutely damaged rat liver:A role for ferritins

AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.

Effects of Phentolamine on Hemorrheology and Hemodynamics in Dogs with Acute Liver Damage

The effects of phentolamine on hemorrheology and hemodynamics were studied in dogs with acute liver damage induced by acetaminophen. After 1 h of phentolamine application , the viscosity of plasma and whole blood was significantly diminished. The hematocrit readings followed the same pattern as the alterations in viscosity. The portal venous resistance and the value of K were remarkably decreased and the portal venous blood flow was obviously increased. It can be assumed , therefore , that the decrease in viscosity induced by phentolamine results from internal hemodilution and phentolamine may improve hepatic blood circulation through the decrease of portal venous resistance caused by the reduction of blood viscosity and the dilation of portal vascular beds.

An Experimental Study on the Disturbance of Liver Circulation and the Change

The changes of hepatic hemodynamics and hemorrheology were investigated in dogs with acute liver damage inducted by acetaminophen There were remarkable disturtance in liver circulation and hemorrheological abnormality occuring in both slight and severe liver damage.The study indicated that the degree of disturbance in liver circulation as well as in lemorheological change is positively correlated with the severity of livei damage For example,marked increase in blood viscosity linked with elevated fibrinogen level appeared in slight liver damage,whereas reduced blood viscosity associated with decreased plasma fibrinogen level and hematocrit occured in severe liver damage.This study also revealed that the inciease of portal venous resistance(PVR)and the disturbance of liver circulation in slight liver damage were chiefly related to the increase of blood viscosity and the increase of PVR in severe liver damage was mainly associated with the reduction of the radius of porta vein.