The effects of p-NaK-tide and SW033299 on nash associated cirrhosis in the rodent

Abstract

Background: NASH and its complications ESLD and HCC have become the second most common cause for liver transplantation in US. The purpose of the present studies was to test the efficacy of two compounds developed by our group, “pNa/K-tide “and “SW033299 “in reversing the liver disturbances produced by NASH. Methods: C57Bl 6J mice (n = 7) were exposed to normal chow (Control -) or high fat diet + fructose (HFD). The mice on HFD was non treated (Control+) or treated with i) p-Na/K- tide, ii) with SW033299 or iii) exposed to an exercise protocol. Livers/plasma were collected “at weeks 7, 12, 16, 20, 24”. Body composition was determined by MRI spectroscopy. The proportion of cells undergoing mitosis or in cell arrest was determined against liver apoptotic index and collagen deposition by standard stains using morphometric techniques. Quantitative protein expression of genes p53, p21, p16, mTOR1, STAT33, SIRT7, FOX01, Grb2 were determined by Western Blots. Metabolic profiles were measured on treated plasma by LC/MS-MS. Results: The total body weight corrected by aging increased significantly in the HFD (HFD vs normal chaw, p < 005 by ANOVA). The amount of liver fat accumulation, the number of cells in senescence and the apoptotic index were significantly decreased in both the pNaK and SW groups when compared to the HFD (p < 00.5 by ANOVA). In addition, the deposition of collagen was significantly lower in the pNaK and SW groups when compared to the HFD group. Glutathione ratio, mitochondrial ß-lipid oxidation function and Na/K-exchange pump activity after censored for aging followed similar trends among groups (p < 0.05 by ANOVA). Metabolic prints were significantly different among groups. Conclusion: pNaK-tide and SW033299 not only prevent but reverse NASH due to high fat diet in the rodent model.