Inhibition Of Liver Regeneration Research Articles

Effects of H2-receptor antagonists on the rat liver after partial hepatectomy or carbon tetrachloride-induced hepatic injury.

A total of 512 male rats were used to investigate the effects of H2-receptor antagonists on the liver after two-thirds hepatectomy or after carbon tetrachloride (CCl4)-induced hepatic injury. The serum aminotransferase levels in hepatectomy rats were significantly elevated as compared with those of rats with the sham operation 1 and 2 days after the operation. However, there were no differences in the serum aminotransferase levels and liver regeneration rates among the groups of hepatectomy rats who were treated with saline, cimetidine, or ranitidine. The injections of cimetidine or ranitidine did not induce a significant increase in serum amino-transferase levels or increase the severity of liver cell necrosis in CCl4-treated rats, as compared with the CCl4-treated rats who received saline injection. Thus, our data indicate that H2-receptor antagonists do not inhibit liver regeneration in rats after two-thirds hepatectomy or exert a detrimental effect on the liver cell necrosis in rats after CCl4-induced hepatic injury.

Inhibition of liver regeneration by chronic alcohol administration.

Liver regeneration is the common mechanism whereby a patient recovers form a liver injury. In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration. We studied the response to a 70% hepatectomy in 240 rats receiving a nutritionally adequate diet containing 36% of their calories as ethanol for three weeks and their pair-fed controls receiving a liquid diet where ethanol is isocalorically replace with carbohydrates. Criteria of liver regeneration were: incorporation of 3H-thymidine in hepatocyte DNA (cpm/10 microgram DNA) and number of hepatocyte labelled nuclei on autoradiography per 100 high power fields. Controls displayed the usual response with peak activity of liver regeneration at 24 hours. Consumption of ethanol was associated with a statistically significant reduction of liver regeneration by both criteria for up to 72 hours after a 70% hepatectomy and delayed the peak of regenerative activity by 24 hours. This inhibiting effect was not related to the presence of alcohol in blood nor to hepatic microsomal enzyme induction by ethanol nor to widespread necrosis of hepatocytes. This effect was reversible after one week of abstinence. This impairment of liver cell renewal by ethanol may be of major significance in the severity and outcome of alcohol-related liver injury.

Effect of acute and chronic ethanol intoxication on hepatic regeneration.

We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats following partial hepatectomy and toxic liver injury produced by D-galactosamine. Ethanol, when administered as a single dose (6 gm/kg), inhibited 3H-thymidine incorporation into hepatic DNA; this effect depended in part on the time of ethanol feeding following partial hepatectomy. Multiple ethanol feedings produced an even greater inhibition, which persisted for at least 48 hr after partial hepatectomy. Rats chronically fed ethanol for 30 days also failed to achieve a hepatic proliferative response to either partial hepatectomy or D-galactosamine induced hepatitis comparable to isocaloric pair-fed controls. These investigations suggest that there may be a certain metabolic state in the hepatocyte cell cycle which is most susceptible to the action(s) of ethanol; inhibition of liver regeneration by acute or chronic ethanol consumption may result in delayed recovery from prior or coincident liver injury.

Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication

We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats after partial hepatectomy and toxic liver injury produced by D-galactosamine. Ethanol, when administered as a single dose (6 g/kg), inhibited 3H-thymidine incorporation into hepatic DNA; this effect depended in part on the time of ethanol feeding after partial hepatectomy. Multiple ethanol feedings produced an even greater inhibition, which persisted for at least 48 hr after partial hepatectomy. Rats chronically fed ethanol for 30 days also failed to achieve a hepatic proliferative response to either partial hepatectomy or D-galactosamine-induced hepatitis, comparable with isocaloric pair-fed controls. These investigations suggest that there may be a certain metabolic state in the hepatocyte cell cycle that is most susceptible to the action(s) of ethanol; inhibition of liver regeneration by acute or chronic ethanol consumption may result in delayed recovery from prior or coincident liver injury.

The inhibition of liver regeneration by the intraportal infusion of fresh serum after partial hepatectomy in the rat.

The inhibition of liver regeneration by the intraportal infusion of fresh serum after partial hepatectomy in the rat.