The effects of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-
carboxylic acid (
SA3443), a novel cyclic
disulfide compound, on the development of chronic liver injury were studied in rats, using two types of models,
carbon tetrachloride (CCl4)-induced chronic liver injury and heterologous serum (swine serum)-induced
liver fibrosis.
SA3443 (30-100 mg/kg, p.o.) significantly suppressed increases in serum
transaminase and
alkaline phosphatase activity induced by CCl4-treatment for 10 weeks. This compound also inhibited increases in hepatic
lipids and
hydroxyproline content in CCl4-treated rats. In the histopathological studies, treatment with
SA3443 resulted in a decrease in the degree of hepatic
necrosis,
fibrosis and steatosis. On the other hand, 8-weeks treatment with swine serum revealed hepatic
fibrosis without appearance of
necrosis or fatty accumulation. In this model,
SA3443 (30 mg/kg, p.o.) reduced the hepatic
hydroxyproline level, and diminished the formation of connective tissue in the liver. These findings indicate that
SA3443 protects the liver against chronic liver
injuries induced by CCl4 and heterogeneous serum.