An Orally-Bioavailable Glutathione-Based Hepatoprotective Compound in Experimental Acute Liver Injury: More Effective than Silymarin and YHK

Many hepatoprotective non-chemical preparations have been recommended as complementary medicine for the treatment of liver disorders. We have utilized a well-defined model of liver injury to study the efficacy of GLU-9599 (a oral bioavailable glutathione-based compound added with selenium, L-cysteine and vitamin C) designed to support liver detox function. Wistar albino rats were divided into five groups. Group I represented the healthy control group; Groups II-IV were given carbon tetrachloride (CCl4) intragastrically. Rats were exposed to CCl4 after they had been pretreated for five days with either saline, silymarin extract, YHK (am herbal Japanese compound with putative hepatoprotective effects) or GLU-9599. After inducing hepatic damage, Group II served as control CCl4; Group III and IV were given silymarin (reference hepatoprotective) and YHK whereas Groups V was administered GLU-9599. Animals were sacrificed 24 hours after receiving CCl4. Liver enzymes and hepatic histology formed the basis for evaluating the efficacy of the treatments. Samples of livers were observed under microscope and electron microscopy (TEM) for the histopathological changes. Levels of marker enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) significantly increased in CCl4 treated rats (Group II). Groups III, IV and V intoxicated with CCl4 and treated with the above hepatoprotective agents showed a significant decrease of the activities of these two enzymes (p<0.05). However, GLU-9599 provided a significantly stronger effect than YHK (p<0.05) and a trend improvement as compared to sylimarin. This was confirmed at histology and TEM whereas the others hepatoprotective compounds had only limited benefits on morphological abnormalities. In conclusion GLU-9599 could be a promising hepatoprotective compound of safe profile although extensive clinical studies are warranted.