Beneficial effect of a controlled Chinese herbal remedy, K-17.22, in CCl4-induced liver toxicity:: an in vivo and in vitro study

The aim of this study was to test K-17.22, an herbal formula which has been preliminarly shown to yield a significant transaminases decrease in HCV patients, in CCl4-induced liver toxicity. Wistar rats were allocated into 3 groups: A) given a s.c. injection of 0.1 mL/100 g body wt mixture of CCl4 in olive oil (1 : 1 v/v) twice a day for 4 weeks; B) as A, plus oral administration of 50 mg/kg of K-17.22 dissolved in 5% glucose; C) as B but with K-17.22 given 1 week after the first injection of CCl4. Rats were sacrificed at the end of the study and blood and liver samples were obtained. As compared to control, group A showed a significant decrease of GSH (> 45%, P <0.001) and GSSG (p <0.01) liver content, a lower liver wet weight (P <0.01) together with an increase of both transaminases (> 15-fold, P < 0.001) whereas both groups B and C showed only a mild transaminases increase (<3-fold, P <0.05). Group A showed a significant decrease of Y-protein fraction and of GST activity, as tested by both substrates (P <0.01 vs control). However, both these parameters were reverted to normal by K-17.22 (P <0.05 vs. A). A parallel in vitro study with hepatocyte culture showed that concentrations as low as 10 mug/mL of K-17.22 were able to significantly mitigate CCl4 hepatocyte damage (P <0.05) comparably to 100 mug/mL silymarin, while 100 mug/mL proved to be more protective than either silymarin 100 mug/mL and of glycyrrhizin 10 mug/mL (P <0.05). These preliminary data suggest that K-17.22 exerts an highly protective and prolonged effect (either preventive and therapeutic) on GSH depletion in CCl4-induced liver injury, thing which might substantiate its potential use in clinical practice.