Effect of Liver Extract Antitoxic fractions on Carbon Tetrachloride-induced Liver Dysfunction in Rats

The detoxification effect of Liver Extract Antitoxic Fractions (LEAFs) on liver injury and dysfunction induced by carbon tetrachloride (CCl₄) was investigated. Female rats were injected intraperitoneally with CCl₄ at a dose of 1 ㎖/㎏ (20% in corn oil, 5 ㎖/㎏). LEAF-B or LEAF-P, originated from bovine and porcine, respectively, was treated subcutaneously at doses of 100, 300 or 500 ㎎/㎏ (10 ㎖/㎏) 4 hr and 30 min prior to as well as 4 hr and 20 hr after CCl₄ challenge. The rats were anesthesized with intraperitoneal injection of urethane (16.5% in saline, 6 ㎖/㎏) 4 hr following final LEAF treatment (24 hr after CCl₄ injection), and administered with bromosulphalein (BSP) solution (1% in saline, 2 ㎖/㎏). The initial biliary excretion time of BSP was recorded, and the blood concentration of BSP was quantified 21 and 46 min after intravenous administration. Also, blood biochemical parameters related to hepatic and renal injuries in accordance with histopathological findings were analyzed. The biliary excretion time of BSP was greatly delayed by CCl₄ injection, which was significantly attenuated by 300-500 ㎎/㎏ of LEAF-B and 100 or 500 ㎎/㎏ of LEAF-P. Also, CCl₄-induced delay in BSP clearance was markedly recovered by 300-500 ㎎/㎏ of LEAF-B or 500 ㎎/㎏ of LEAF-P. In addition, CCl₄-induced changes in blood biochemical markers related to hepatic and renal injuries were remarkably reversed by LEAF-B or LEAF-P in a dose-dependent manner. Such effects of LEAFs on liver dysfunction were in parallel with the histopathological findings of the liver. That is, CCl₄ caused centrilobular congestion, hepatocytic degeneration, lipid droplets and immflamatory cell infiltration, resulting in disintegration of hepatic cords. Interestingly, such lesions were attenuated by LEAFs treatment, reducing mean lesion scores from 2.30 in rats administered with CCl₄ alone to 1.75 and 1.65 in animals treated with 500 ㎎/㎏ of LEAF-B and LEAF-P, respectively. Taken together, it is suggested that LEAFs might have protective effects against hepatic and renal cytotoxicity and dysfunction including impairments of hepatic biosynthesis, biliary excretion, metabolism and filtration induced by CCl₄, and that the effecacy of LEAF-P is comparable to that of LEAF-B which is avaliable in clinics.