Bioartificial Liver Using Hepatocytes on Biosilon Microcamers: Treatment of Chemically Induced Acute Hepatic Failure in Rats

Abstract

An artificial liver support procedure based on hemoperfusion via hepatocytes cultured on microcarriers is described. The efficiency of the system was assessed by the survival rate of rats treated with either lethal dosage of 7% CCl4 [30 ml/kg body weight (b.w.)] or D-galactosamine (2.5 g/kg b.w.). In CCl4-treated rats, hemoperfusion via empty microcarriers (n = 16) revealed no surviving animals, whereas the use of the bioartificial liver (n = 11) resulted in 80% (p less than 0.01) and 60% (p less than 0.05) survival 48 and 168 h after hepatotoxin, respectively. For the same time periods, the survival rate in D-galactosamine-intoxicated rats after hemoperfusion with hepatocytes (n = 20) was approximately 60% (p less than 0.05) and was only 5% in those of rats treated with empty microcarriers (n = 20). Sublethal dosage of 7% CCl4 (15 ml/kg b.w.) caused 25% mortality and prolonged (48 h) increase of activity of the liver enzymes and bilirubin levels in the serum of surviving animals. In these rats (n = 8) at the end of 3 h of hemoperfusion via hepatocytes, the bilirubin concentration decreased by 45% as compared with the control group (n = 6) treated with empty microcarriers. Moreover, by 48 h after intoxication, the use of the bioartificial liver resulted in more than a three-fold decrease in glutamate-oxaloacetate transaminase and a 10-fold decrease in glutamate-pyruvate transaminase serum activity as well as a fivefold decline in total and a ninefold decline in conjugated bilirubin levels as compared with the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)